Brief Summary
This phase I/II trial studies the side effects and the best dose of brentuximab vedotin when given together with gemcitabine hydrochloride and to see how well they work in treating younger patients with Hodgkin lymphoma that has returned or does not respond to treatment. Monoclonal antibodies, such as brentuximab vedotin, may find cancer cells and help kill them. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving brentuximab vedotin together with gemcitabine hydrochloride may kill more cancer cells.
Brief Title
Brentuximab Vedotin and Gemcitabine Hydrochloride in Treating Younger Patients With Relapsed or Refractory Hodgkin Lymphoma
Detailed Description
PRIMARY OBJECTIVES:
I. To estimate the maximum tolerated dose (MTD) and/or recommended Phase 2 dose of brentuximab vedotin in combination with gemcitabine administered every three weeks to children with relapsed or primary refractory Hodgkin lymphoma (HL).
II. To define and describe the toxicities of brentuximab vedotin in combination with gemcitabine administered on this schedule.
III. To determine the complete response (CR) rate after treatment with four cycles of gemcitabine with brentuximab vedotin among patients with relapsed or refractory HL.
SECONDARY OBJECTIVES:
I. To preliminarily define the antitumor activity of brentuximab vedotin in combination with gemcitabine within the confines of a Phase 1 study.
II. To describe the overall response rate (ORR) after 4 cycles of therapy among patients with relapsed or refractory HL.
III. To describe the proportion of patients with HL able to mobilize an adequate yield of cluster of differentiation (CD) 34+ stem cells after gemcitabine with brentuximab vedotin.
IV. To describe the relationship between disease response among patients with HL and changes in thymus and activation-regulated chemokine (TARC) during treatment, and to determine if specific micro ribonucleic acid (miRNA) profiles correlate with response to treatment.
V. To describe the frequency of the Fc gamma receptor IIIa (FcγRIIIa)-158 valine (V)/phenylalanine (F) polymorphism among patients who experience pulmonary toxicity on this protocol.
OUTLINE: This is a phase I, dose-escalation study of brentuximab vedotin followed by a phase II study. (Phase I completed as of amendment 4)
Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1 and gemcitabine hydrochloride IV over 100 minutes on days 1 and 8. Treatment repeats every 21 days for up to 15 more courses in the absence of disease progression or unacceptable toxicity. Patients with CR after any course may go off protocol therapy for stem cell transplant.
After completion of study treatment, patients are followed up at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months.
I. To estimate the maximum tolerated dose (MTD) and/or recommended Phase 2 dose of brentuximab vedotin in combination with gemcitabine administered every three weeks to children with relapsed or primary refractory Hodgkin lymphoma (HL).
II. To define and describe the toxicities of brentuximab vedotin in combination with gemcitabine administered on this schedule.
III. To determine the complete response (CR) rate after treatment with four cycles of gemcitabine with brentuximab vedotin among patients with relapsed or refractory HL.
SECONDARY OBJECTIVES:
I. To preliminarily define the antitumor activity of brentuximab vedotin in combination with gemcitabine within the confines of a Phase 1 study.
II. To describe the overall response rate (ORR) after 4 cycles of therapy among patients with relapsed or refractory HL.
III. To describe the proportion of patients with HL able to mobilize an adequate yield of cluster of differentiation (CD) 34+ stem cells after gemcitabine with brentuximab vedotin.
IV. To describe the relationship between disease response among patients with HL and changes in thymus and activation-regulated chemokine (TARC) during treatment, and to determine if specific micro ribonucleic acid (miRNA) profiles correlate with response to treatment.
V. To describe the frequency of the Fc gamma receptor IIIa (FcγRIIIa)-158 valine (V)/phenylalanine (F) polymorphism among patients who experience pulmonary toxicity on this protocol.
OUTLINE: This is a phase I, dose-escalation study of brentuximab vedotin followed by a phase II study. (Phase I completed as of amendment 4)
Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1 and gemcitabine hydrochloride IV over 100 minutes on days 1 and 8. Treatment repeats every 21 days for up to 15 more courses in the absence of disease progression or unacceptable toxicity. Patients with CR after any course may go off protocol therapy for stem cell transplant.
After completion of study treatment, patients are followed up at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Recurrent Adult Hodgkin Lymphoma
Recurrent Childhood Hodgkin Lymphoma
Refractory Childhood Hodgkin Lymphoma
Eligibility Criteria
Inclusion Criteria:
* Patients must have had histologic verification of the malignancy at original diagnosis; patients must have histologic verification of recurrent Hodgkin disease at the time of relapse; no additional biopsy is required for patients with primary refractory disease (i.e. no prior CR)
* PARTS A AND B: Patients with Hodgkin lymphoma (HL) are eligible for both the phase 1 and 2 portions, if they are in one of the following categories:
* Primary refractory disease (i.e. no prior CR)
* Very early relapse (\< 6 months from the end of initial therapy, including chemotherapy ± radiation)
* Advanced stage (III or IV) at diagnosis who relapse less than one year from the end of initial therapy
* Note that patients with low-stage disease (IA or IIA) at initial diagnosis, who were treated with radiation alone or fewer than four cycles of chemotherapy will NOT be eligible
* Patients must have measurable disease, documented by clinical and radiographic criteria
* Patients must have a life expectancy of \>= 8 weeks (\>= 56 days)
* Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50 for patients =\< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy
* At least 14 days after the last dose of myelosuppressive chemotherapy (28 days if prior nitrosourea); Note: cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of therapy
* At least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
* At least 7 days after the last dose of a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
* At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
* At least 3 half-lives of the antibody after the last dose of a monoclonal antibody
* At least 14 days after local palliative radiation therapy (XRT) (small port); at least 150 days must have elapsed if prior total body irradiation (TBI), craniospinal XRT or if \>= 50% radiation of pelvis; at least 42 days must have elapsed if other substantial bone marrow (BM) radiation
* Patients with prior autologous or allogeneic stem cell transplant (SCT) are excluded from this study
* At least 28 days must have elapsed since the most recent dose of bleomycin, to allow adequate time to detect evidence of bleomycin-related pulmonary toxicity
* PART A: FOR PATIENTS WITH KNOWN BONE MARROW INVOLVEMENT (Completed as of Amendment 4)
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL
* Platelet count \>= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
* PART B: FOR PATIENTS WITHOUT KNOWN BONE MARROW INVOLVEMENT
* Peripheral absolute neutrophil count (ANC) \>= 750/uL
* Platelet count \>= 75,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
* Patients with lymphoma metastatic to bone marrow who have granulocytopenia, anemia, and/or thrombocytopenia will be eligible for study but not evaluable for hematologic toxicity (in Part A, there will be a maximum of one per cohort); such patients must meet the blood counts as in Part A (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); if dose-limiting hematologic toxicity is observed, all subsequent patients enrolled in Part A must be evaluable for hematologic toxicity
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 ml/min/1.73 m\^2 OR
* A serum creatinine based on age/gender as follows:
* =\< 0.6 mg/dL (for 1 to \< 2 years of age)
* =\< 0.8 mg/dL (for 2 to \< 6 years of age)
* =\< 1.0 mg/dL (for 6 to \< 10 years of age)
* =\< 1.2 mg/dL (for 10 to \< 13 years of age)
* =\< 1.4 mg/dL (for females \>= 13 years of age)
* =\< 1.5 mg/dL (for males 13 to \< 16 years of age)
* =\< 1.7 mg/dL (for males \>= 16 years of age)
* Bilirubin (sum of conjugated + unconjugated) =\< 1.5 x upper limit of normal (ULN) for age
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) \< 2.5 x upper limit of normal (ULN) for age; for the purpose of this study, the ULN for SGPT is 45 U/L
* Serum albumin \>= 2 g/dL
* No evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficiency, and a pulse oximetry \> 92% while breathing room air
* Forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) \> 60% by pulmonary function test (PFT), unless due to large mediastinal mass from HL; carbon monoxide diffusion capacity (DLCO), FEV1, and forced vital capacity all \> 50% predicted value; Note: pulmonary function testing is not required for children \< 8 years old, or for any child who is developmentally unable to comply with pulmonary function testing
* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
* Nervous system disorders (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\] 4) resulting from prior therapy must be \< grade 2
Exclusion Criteria:
* Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during protocol therapy and for at least 30 days after the last dose of brentuximab vedotin; abstinence is an acceptable method of birth control
* Concomitant medications
* Patients receiving stable or decreasing corticosteroids are not eligible for other concurrent conditions (e.g. asthma, autoimmune diseases, rash, documented adrenal insufficiency) are eligible for this study
* Patients who are currently receiving another investigational drug are not eligible
* Patients who are currently receiving other anti-cancer agents are not eligible
* Patients who have an uncontrolled infection are not eligible
* Patients with an immunodeficiency that existed prior to diagnosis, such as primary immunodeficiency syndromes, organ transplant recipients and children on current systemic immunosuppressive agents are not eligible
* Patients known to be positive for human immunodeficiency virus (HIV) are not eligible
* Prior therapy
* Patients with prior exposure to brentuximab vedotin are not eligible; NOTE: prior exposure to gemcitabine is NOT an exclusion criterion
* Patients who have undergone prior autologous or allogeneic SCT are not eligible
* Patients with HL who were stage IA or IIA at initial diagnosis and treated with either radiation alone or \< 4 cycles of chemotherapy are not eligible
* Patients who have received a prior solid organ transplantation are not eligible
* Patients with known hypersensitivity to Escherichia coli (E.coli)-derived proteins, filgrastim, or any component of filgrastim are not eligible
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
* Patients must have had histologic verification of the malignancy at original diagnosis; patients must have histologic verification of recurrent Hodgkin disease at the time of relapse; no additional biopsy is required for patients with primary refractory disease (i.e. no prior CR)
* PARTS A AND B: Patients with Hodgkin lymphoma (HL) are eligible for both the phase 1 and 2 portions, if they are in one of the following categories:
* Primary refractory disease (i.e. no prior CR)
* Very early relapse (\< 6 months from the end of initial therapy, including chemotherapy ± radiation)
* Advanced stage (III or IV) at diagnosis who relapse less than one year from the end of initial therapy
* Note that patients with low-stage disease (IA or IIA) at initial diagnosis, who were treated with radiation alone or fewer than four cycles of chemotherapy will NOT be eligible
* Patients must have measurable disease, documented by clinical and radiographic criteria
* Patients must have a life expectancy of \>= 8 weeks (\>= 56 days)
* Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50 for patients =\< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy
* At least 14 days after the last dose of myelosuppressive chemotherapy (28 days if prior nitrosourea); Note: cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of therapy
* At least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
* At least 7 days after the last dose of a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
* At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
* At least 3 half-lives of the antibody after the last dose of a monoclonal antibody
* At least 14 days after local palliative radiation therapy (XRT) (small port); at least 150 days must have elapsed if prior total body irradiation (TBI), craniospinal XRT or if \>= 50% radiation of pelvis; at least 42 days must have elapsed if other substantial bone marrow (BM) radiation
* Patients with prior autologous or allogeneic stem cell transplant (SCT) are excluded from this study
* At least 28 days must have elapsed since the most recent dose of bleomycin, to allow adequate time to detect evidence of bleomycin-related pulmonary toxicity
* PART A: FOR PATIENTS WITH KNOWN BONE MARROW INVOLVEMENT (Completed as of Amendment 4)
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL
* Platelet count \>= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
* PART B: FOR PATIENTS WITHOUT KNOWN BONE MARROW INVOLVEMENT
* Peripheral absolute neutrophil count (ANC) \>= 750/uL
* Platelet count \>= 75,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
* Patients with lymphoma metastatic to bone marrow who have granulocytopenia, anemia, and/or thrombocytopenia will be eligible for study but not evaluable for hematologic toxicity (in Part A, there will be a maximum of one per cohort); such patients must meet the blood counts as in Part A (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); if dose-limiting hematologic toxicity is observed, all subsequent patients enrolled in Part A must be evaluable for hematologic toxicity
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 ml/min/1.73 m\^2 OR
* A serum creatinine based on age/gender as follows:
* =\< 0.6 mg/dL (for 1 to \< 2 years of age)
* =\< 0.8 mg/dL (for 2 to \< 6 years of age)
* =\< 1.0 mg/dL (for 6 to \< 10 years of age)
* =\< 1.2 mg/dL (for 10 to \< 13 years of age)
* =\< 1.4 mg/dL (for females \>= 13 years of age)
* =\< 1.5 mg/dL (for males 13 to \< 16 years of age)
* =\< 1.7 mg/dL (for males \>= 16 years of age)
* Bilirubin (sum of conjugated + unconjugated) =\< 1.5 x upper limit of normal (ULN) for age
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) \< 2.5 x upper limit of normal (ULN) for age; for the purpose of this study, the ULN for SGPT is 45 U/L
* Serum albumin \>= 2 g/dL
* No evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficiency, and a pulse oximetry \> 92% while breathing room air
* Forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) \> 60% by pulmonary function test (PFT), unless due to large mediastinal mass from HL; carbon monoxide diffusion capacity (DLCO), FEV1, and forced vital capacity all \> 50% predicted value; Note: pulmonary function testing is not required for children \< 8 years old, or for any child who is developmentally unable to comply with pulmonary function testing
* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
* Nervous system disorders (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\] 4) resulting from prior therapy must be \< grade 2
Exclusion Criteria:
* Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during protocol therapy and for at least 30 days after the last dose of brentuximab vedotin; abstinence is an acceptable method of birth control
* Concomitant medications
* Patients receiving stable or decreasing corticosteroids are not eligible for other concurrent conditions (e.g. asthma, autoimmune diseases, rash, documented adrenal insufficiency) are eligible for this study
* Patients who are currently receiving another investigational drug are not eligible
* Patients who are currently receiving other anti-cancer agents are not eligible
* Patients who have an uncontrolled infection are not eligible
* Patients with an immunodeficiency that existed prior to diagnosis, such as primary immunodeficiency syndromes, organ transplant recipients and children on current systemic immunosuppressive agents are not eligible
* Patients known to be positive for human immunodeficiency virus (HIV) are not eligible
* Prior therapy
* Patients with prior exposure to brentuximab vedotin are not eligible; NOTE: prior exposure to gemcitabine is NOT an exclusion criterion
* Patients who have undergone prior autologous or allogeneic SCT are not eligible
* Patients with HL who were stage IA or IIA at initial diagnosis and treated with either radiation alone or \< 4 cycles of chemotherapy are not eligible
* Patients who have received a prior solid organ transplantation are not eligible
* Patients with known hypersensitivity to Escherichia coli (E.coli)-derived proteins, filgrastim, or any component of filgrastim are not eligible
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Inclusion Criteria
Inclusion Criteria:
* Patients must have had histologic verification of the malignancy at original diagnosis; patients must have histologic verification of recurrent Hodgkin disease at the time of relapse; no additional biopsy is required for patients with primary refractory disease (i.e. no prior CR)
* PARTS A AND B: Patients with Hodgkin lymphoma (HL) are eligible for both the phase 1 and 2 portions, if they are in one of the following categories:
* Primary refractory disease (i.e. no prior CR)
* Very early relapse (\< 6 months from the end of initial therapy, including chemotherapy ± radiation)
* Advanced stage (III or IV) at diagnosis who relapse less than one year from the end of initial therapy
* Note that patients with low-stage disease (IA or IIA) at initial diagnosis, who were treated with radiation alone or fewer than four cycles of chemotherapy will NOT be eligible
* Patients must have measurable disease, documented by clinical and radiographic criteria
* Patients must have a life expectancy of \>= 8 weeks (\>= 56 days)
* Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50 for patients =\< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy
* At least 14 days after the last dose of myelosuppressive chemotherapy (28 days if prior nitrosourea); Note: cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of therapy
* At least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
* At least 7 days after the last dose of a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
* At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
* At least 3 half-lives of the antibody after the last dose of a monoclonal antibody
* At least 14 days after local palliative radiation therapy (XRT) (small port); at least 150 days must have elapsed if prior total body irradiation (TBI), craniospinal XRT or if \>= 50% radiation of pelvis; at least 42 days must have elapsed if other substantial bone marrow (BM) radiation
* Patients with prior autologous or allogeneic stem cell transplant (SCT) are excluded from this study
* At least 28 days must have elapsed since the most recent dose of bleomycin, to allow adequate time to detect evidence of bleomycin-related pulmonary toxicity
* PART A: FOR PATIENTS WITH KNOWN BONE MARROW INVOLVEMENT (Completed as of Amendment 4)
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL
* Platelet count \>= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
* PART B: FOR PATIENTS WITHOUT KNOWN BONE MARROW INVOLVEMENT
* Peripheral absolute neutrophil count (ANC) \>= 750/uL
* Platelet count \>= 75,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
* Patients with lymphoma metastatic to bone marrow who have granulocytopenia, anemia, and/or thrombocytopenia will be eligible for study but not evaluable for hematologic toxicity (in Part A, there will be a maximum of one per cohort); such patients must meet the blood counts as in Part A (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); if dose-limiting hematologic toxicity is observed, all subsequent patients enrolled in Part A must be evaluable for hematologic toxicity
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 ml/min/1.73 m\^2 OR
* A serum creatinine based on age/gender as follows:
* =\< 0.6 mg/dL (for 1 to \< 2 years of age)
* =\< 0.8 mg/dL (for 2 to \< 6 years of age)
* =\< 1.0 mg/dL (for 6 to \< 10 years of age)
* =\< 1.2 mg/dL (for 10 to \< 13 years of age)
* =\< 1.4 mg/dL (for females \>= 13 years of age)
* =\< 1.5 mg/dL (for males 13 to \< 16 years of age)
* =\< 1.7 mg/dL (for males \>= 16 years of age)
* Bilirubin (sum of conjugated + unconjugated) =\< 1.5 x upper limit of normal (ULN) for age
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) \< 2.5 x upper limit of normal (ULN) for age; for the purpose of this study, the ULN for SGPT is 45 U/L
* Serum albumin \>= 2 g/dL
* No evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficiency, and a pulse oximetry \> 92% while breathing room air
* Forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) \> 60% by pulmonary function test (PFT), unless due to large mediastinal mass from HL; carbon monoxide diffusion capacity (DLCO), FEV1, and forced vital capacity all \> 50% predicted value; Note: pulmonary function testing is not required for children \< 8 years old, or for any child who is developmentally unable to comply with pulmonary function testing
* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
* Nervous system disorders (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\] 4) resulting from prior therapy must be \< grade 2
* Patients must have had histologic verification of the malignancy at original diagnosis; patients must have histologic verification of recurrent Hodgkin disease at the time of relapse; no additional biopsy is required for patients with primary refractory disease (i.e. no prior CR)
* PARTS A AND B: Patients with Hodgkin lymphoma (HL) are eligible for both the phase 1 and 2 portions, if they are in one of the following categories:
* Primary refractory disease (i.e. no prior CR)
* Very early relapse (\< 6 months from the end of initial therapy, including chemotherapy ± radiation)
* Advanced stage (III or IV) at diagnosis who relapse less than one year from the end of initial therapy
* Note that patients with low-stage disease (IA or IIA) at initial diagnosis, who were treated with radiation alone or fewer than four cycles of chemotherapy will NOT be eligible
* Patients must have measurable disease, documented by clinical and radiographic criteria
* Patients must have a life expectancy of \>= 8 weeks (\>= 56 days)
* Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50 for patients =\< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy
* At least 14 days after the last dose of myelosuppressive chemotherapy (28 days if prior nitrosourea); Note: cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of therapy
* At least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
* At least 7 days after the last dose of a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
* At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
* At least 3 half-lives of the antibody after the last dose of a monoclonal antibody
* At least 14 days after local palliative radiation therapy (XRT) (small port); at least 150 days must have elapsed if prior total body irradiation (TBI), craniospinal XRT or if \>= 50% radiation of pelvis; at least 42 days must have elapsed if other substantial bone marrow (BM) radiation
* Patients with prior autologous or allogeneic stem cell transplant (SCT) are excluded from this study
* At least 28 days must have elapsed since the most recent dose of bleomycin, to allow adequate time to detect evidence of bleomycin-related pulmonary toxicity
* PART A: FOR PATIENTS WITH KNOWN BONE MARROW INVOLVEMENT (Completed as of Amendment 4)
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL
* Platelet count \>= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
* PART B: FOR PATIENTS WITHOUT KNOWN BONE MARROW INVOLVEMENT
* Peripheral absolute neutrophil count (ANC) \>= 750/uL
* Platelet count \>= 75,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
* Patients with lymphoma metastatic to bone marrow who have granulocytopenia, anemia, and/or thrombocytopenia will be eligible for study but not evaluable for hematologic toxicity (in Part A, there will be a maximum of one per cohort); such patients must meet the blood counts as in Part A (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); if dose-limiting hematologic toxicity is observed, all subsequent patients enrolled in Part A must be evaluable for hematologic toxicity
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 ml/min/1.73 m\^2 OR
* A serum creatinine based on age/gender as follows:
* =\< 0.6 mg/dL (for 1 to \< 2 years of age)
* =\< 0.8 mg/dL (for 2 to \< 6 years of age)
* =\< 1.0 mg/dL (for 6 to \< 10 years of age)
* =\< 1.2 mg/dL (for 10 to \< 13 years of age)
* =\< 1.4 mg/dL (for females \>= 13 years of age)
* =\< 1.5 mg/dL (for males 13 to \< 16 years of age)
* =\< 1.7 mg/dL (for males \>= 16 years of age)
* Bilirubin (sum of conjugated + unconjugated) =\< 1.5 x upper limit of normal (ULN) for age
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) \< 2.5 x upper limit of normal (ULN) for age; for the purpose of this study, the ULN for SGPT is 45 U/L
* Serum albumin \>= 2 g/dL
* No evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficiency, and a pulse oximetry \> 92% while breathing room air
* Forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) \> 60% by pulmonary function test (PFT), unless due to large mediastinal mass from HL; carbon monoxide diffusion capacity (DLCO), FEV1, and forced vital capacity all \> 50% predicted value; Note: pulmonary function testing is not required for children \< 8 years old, or for any child who is developmentally unable to comply with pulmonary function testing
* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
* Nervous system disorders (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\] 4) resulting from prior therapy must be \< grade 2
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
30 Years
Minimum Age
13 Months
NCT Id
NCT01780662
Org Class
Nih
Org Full Name
National Cancer Institute (NCI)
Org Study Id
NCI-2013-00107
Overall Status
Completed
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 1/2 Study of Brentuximab Vedotin (SGN35) in Combination With Gemcitabine for Pediatric and Young Adult Patients With Relapsed or Refractory Hodgkin Lymphoma
Primary Outcomes
Outcome Description
MTD was determined as the maximum dose at which fewer than one-third of patients experience Dose Limiting Toxicities (DLT) as assessed by National Cancer Institute (NCI) CTCAE v 4.0 during Cycle 1 of therapy. Gemcitabine was administered on days 1 and 8 of a 21 day cycle at a fixed dose. Brentuximab vedotin was investigated at a starting dose of 1.4 mg/kg administered on day 1 and escalated if tolerated.
Outcome Measure
Maximum Tolerated Dose (MTD) for Brentuximab Vedotin
Outcome Time Frame
During cycle 1 of protocol therapy (21 days)
Outcome Description
The number of eligible patients assigned to receive brentuximab vedotin in combination with gemcitabine that experienced CTC Version 4, grade 3 or higher adverse events during Phase 1 and Phase 2.
Outcome Measure
Adverse Events Graded According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Outcome Time Frame
13 months from first dose
Outcome Description
The number of patients who experienced complete Response (CR) within the first four cycles. By modern response criteria, those with partial response (PR) or stable disease with all target lesions with Deauville scores \<=3 after cycle 4 are also considered as CR. Patients were assessed after treatment with four cycles of gemcitabine with brentuximab vedotin. CR was only reported for Dose level 2 across both phases of study.
Outcome Measure
The Number of Patients With Relapsed or Refractory HL Who Achieved Complete Response (CR)
Outcome Time Frame
After 4 cycles (21 days per cycle) of protocol therapy
Secondary Ids
Secondary Id
NCI-2013-00107
Secondary Id
AHOD1221
Secondary Id
COG-AHOD1221
Secondary Id
AHOD1221
Secondary Id
AHOD1221
Secondary Id
U10CA180886
Secondary Id
UM1CA097452
Secondary Outcomes
Outcome Description
The Deauville five-point scale was used to assess the number of participants with complete response (CR) and partial response (PR). A lower score indicates a better outcome. Scores of 1-3 represent CR and 4-5 represent PR.
Outcome Time Frame
Up to 13 months from first dose
Outcome Measure
The Number of Patients Who Had Disease Response Assessed by Deauville Scales Among Those in Phase I With Dose Level 2.
Outcome Description
The percentage of patients who experienced complete Response (CR) within the first four cycles.By modern response criteria, those with partial response (PR) or stable disease with all target lesions with Deauville scores \<=3 after cycle 4 are also considered as CR. Patients were assessed after treatment with four cycles of gemcitabine with brentuximab vedotin. CR was only reported for Dose level 2 across both phases of study.
Outcome Time Frame
After 4 cycles (21 days per cycle) of protocol therapy
Outcome Measure
Percentage of Patients Who Achieved Overall Response (OR) as Measured by Complete Response (CR) and Partial Response (PR)
Outcome Description
Successful PBSC collection was defined as a collection of more than 2x10\^6 CD34 positive cells.
Outcome Time Frame
From 1 to 5 cycles
Outcome Measure
The Number of Patients Who Had Successful Peripheral Blood Stem Cell (PBSC) Collection
Outcome Description
Limit to 41 evaluable patients who received dose 1.8 mg/kg
Outcome Time Frame
From baseline to time prior to cycle 2
Outcome Measure
Plasma Level of Thymus and Activation-Regulated Chemokine (TARC)
Outcome Description
Limit to 41 evaluable patients who received dose 1.8 mg/kg
Outcome Time Frame
From the end of first dose to the end of last dose (Up to 13 Months)
Outcome Measure
Correlation Between Micro Ribonucleic Acid (miRNA) and Disease Response to Protocol Treatment
Outcome Description
Among patients who received 1.8mg/kg dose, the frequency of the FcγRIIIa-158 V/F polymorphism are described.
Outcome Time Frame
From the end of first dose to the end of last dose (Up to 13 Months)
Outcome Measure
Number of Patients With FcyRIIIa-158 V/F (Valine/Phenylalanine) Polymorphism
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Maximum Age Number (converted to Years and rounded down)
30
Minimum Age Number (converted to Years and rounded down)
1
Investigators
Investigator Type
Principal Investigator
Investigator Name
Jonathan Gill
Investigator Email
jgill@montefiore.org
Investigator Phone
718-741-2331
Categories Mesh Debug
Cancer --- NEOPLASMS
Blood & Bone Marrow Cancers --- LYMPHOPROLIFERATIVE DISORDERS
Blood & Bone Marrow Cancers --- LYMPHATIC DISEASES
Blood & Bone Marrow Cancers --- IMMUNOPROLIFERATIVE DISORDERS
Infectious Disease --- IMMUNE SYSTEM DISEASES
Lung --- IMMUNE SYSTEM DISEASES
MeSH Terms
HODGKIN DISEASE
LYMPHOMA
NEOPLASMS BY HISTOLOGIC TYPE
NEOPLASMS
LYMPHOPROLIFERATIVE DISORDERS
LYMPHATIC DISEASES
HEMIC AND LYMPHATIC DISEASES
IMMUNOPROLIFERATIVE DISORDERS
IMMUNE SYSTEM DISEASES
BRENTUXIMAB VEDOTIN
GEMCITABINE
OLIGOPEPTIDES
PEPTIDES
AMINO ACIDS, PEPTIDES, AND PROTEINS
ANTIBODIES, MONOCLONAL, HUMANIZED
ANTIBODIES, MONOCLONAL
ANTIBODIES
IMMUNOGLOBULINS
IMMUNOPROTEINS
BLOOD PROTEINS
PROTEINS
SERUM GLOBULINS
GLOBULINS
HETEROCYCLIC COMPOUNDS
DEOXYCYTIDINE
CYTIDINE
PYRIMIDINE NUCLEOSIDES
PYRIMIDINES
HETEROCYCLIC COMPOUNDS, 1-RING