Brief Summary
The Phase I part of the study aims to evaluate the safety, efficacy, and tolerability of subcutaneous (SC) blinatumomab for treatment of Relapsed or Refractory B cell Precursor Acute Lymphoblastic Leukemia (R/R B-ALL), to determine the maximum tolerated dose (MTD), and recommended phase 2 dose(s) (RP2D) of SC administered blinatumomab.
The Phase II part of the study will evaluate the safety, efficacy, and tolerability of SC blinatumomab for treatment of R/R B-ALL and Minimum Residual Disease Positive (MRD+) B-ALL in participants 12 years old and greater. It will also conduct a clinical pharmacokinetic (PK) evaluation of SC1 and SC2 blinatumomab formulations.
The Phase II part of the study will evaluate the safety, efficacy, and tolerability of SC blinatumomab for treatment of R/R B-ALL and Minimum Residual Disease Positive (MRD+) B-ALL in participants 12 years old and greater. It will also conduct a clinical pharmacokinetic (PK) evaluation of SC1 and SC2 blinatumomab formulations.
Brief Title
A Study of Subcutaneous Blinatumomab Administration in Participants With R/R and MRD+ B-ALL
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
866-572-6436
Central Contact Email
medinfo@amgen.com
Completion Date
Completion Date Type
Estimated
Conditions
B Cell Precursor Acute Lymphoblastic Leukemia
Eligibility Criteria
Inclusion Criteria:
* Ph-IIC, Dose Escalation and Dose Expansion: Aged 18 years or older (or same or greater than legal age within the country if it is older than 18 years).
* Ph-IIRa and Ph-IIMa: Aged ≥ 17 years at time of informed consent.
* Ph-IIRb and Ph-IIMb: Age ≥ 12 years and \< 17 years at time of informed consent.
* Ph-IIR, Ph-IIC, Dose escalation, Dose Expansion: Participants with R/R B-precursor ALL.
* Relapsed or Refractory B-precursor ALL at any time after first salvage therapy.
* Relapsed B-precursor ALL at any time after allogenic hematopoietic stem cell transplant (HSCT).
* Ph-IIR, Ph-IIC, Dose escalation, Dose expansion: Greater than or equal to 5% blasts in the Bone Marrow per local assessment.
* Ph-IIM: B-precursor ALL and bone marrow blasts (BMB) ≥ 0.01% and \< 5% per local assessment.
* Ph-IIM: Availability of an appropriate archival BM specimen from initial or relapse diagnosis and the screening BM sample.
* Participants aged ≥ 18 years: Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2.
* Participants aged 16 to \< 18 years old: Karnofsky Performance Score ≥ 50%.
* Participants aged \< 16 years old: Lansky Performance Score ≥ 50%.
* Any Ph+ participant intolerant or refractory to prior tyrosine kinase inhibitors (TKIs) are eligible.
* Ph-IIM: BM function as follows:
* Absolute Neutrophil Count (ANC) ≥ 500/μL
* Platelet count ≥ 50 000/μL (transfusion permitted)
* Hemoglobin level ≥ 9 g/dL (transfusion permitted)
The above is a summary, other inclusion criteria details may apply.
Exclusion Criteria:
* Active ALL in the central nervous system (CNS). Presence of greater than 5 white blood cells per cubic millimeter in cerebrospinal fluid (CSF) with lymphoblasts present and/or clinical signs of CNS leukemia. If CSF leukemia is present subjects will have to receive intrathecal therapy and have documented negative CSF prior to enrolling.
* History or presence of clinically relevant CNS pathology (excluding headache) such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis or severe (≥ grade 3) CNS events including immune effector cell-associated neurotoxicity syndrome (ICANS) from prior chimeric antigen receptor T-cell (CAR T) or other T cell engager therapies.
* Isolated Extramedullary (EM) Disease.
* For Ph-IIM only: Current EM disease or presence of circulating leukemia blasts.
* Current autoimmune disease or history of autoimmune disease with potential CNS involvement.
* Active acute or chronic graft versus host disease requiring systemic treatment with immunosuppressive medication.
* Symptoms and/or signs that indicate an acute or uncontrolled chronic infection, any other disease or condition that could be exacerbated by the treatment or would complicate protocol compliance.
* Testicular leukemia.
* History of malignancy (with certain exceptions) other than ALL within 3 years prior to start of protocol-specified therapy.
* Allogeneic HSCT within 12 weeks before the start of protocol-specified therapy.
* Cancer chemotherapy within 2 weeks before the start of protocol-specified therapy (with certain exceptions).
* Immunotherapy within 4 weeks before start of protocol-specified therapy.
* Prior failed cluster of differentiation (CD19) directed therapy such as prior blinatumomab or CD19 CAR T cells will be allowed (with demonstrated continued CD19+ expression), if treatment ended more than 4 weeks prior to start of protocol therapy and no prior CNS complications.
* Currently receiving treatment in or less than 30 days or 5 half-lives since ending treatment on another investigational study(ies).
* Abnormal screening laboratory parameters.
* Female participant: Pregnant or breastfeeding or planning to become pregnant or donate eggs, or expected to breastfeed during treatment and for 96 hours after the last dose of investigational product (SC blinatumomab).
The above is a summary, other exclusion criteria details may apply.
* Ph-IIC, Dose Escalation and Dose Expansion: Aged 18 years or older (or same or greater than legal age within the country if it is older than 18 years).
* Ph-IIRa and Ph-IIMa: Aged ≥ 17 years at time of informed consent.
* Ph-IIRb and Ph-IIMb: Age ≥ 12 years and \< 17 years at time of informed consent.
* Ph-IIR, Ph-IIC, Dose escalation, Dose Expansion: Participants with R/R B-precursor ALL.
* Relapsed or Refractory B-precursor ALL at any time after first salvage therapy.
* Relapsed B-precursor ALL at any time after allogenic hematopoietic stem cell transplant (HSCT).
* Ph-IIR, Ph-IIC, Dose escalation, Dose expansion: Greater than or equal to 5% blasts in the Bone Marrow per local assessment.
* Ph-IIM: B-precursor ALL and bone marrow blasts (BMB) ≥ 0.01% and \< 5% per local assessment.
* Ph-IIM: Availability of an appropriate archival BM specimen from initial or relapse diagnosis and the screening BM sample.
* Participants aged ≥ 18 years: Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2.
* Participants aged 16 to \< 18 years old: Karnofsky Performance Score ≥ 50%.
* Participants aged \< 16 years old: Lansky Performance Score ≥ 50%.
* Any Ph+ participant intolerant or refractory to prior tyrosine kinase inhibitors (TKIs) are eligible.
* Ph-IIM: BM function as follows:
* Absolute Neutrophil Count (ANC) ≥ 500/μL
* Platelet count ≥ 50 000/μL (transfusion permitted)
* Hemoglobin level ≥ 9 g/dL (transfusion permitted)
The above is a summary, other inclusion criteria details may apply.
Exclusion Criteria:
* Active ALL in the central nervous system (CNS). Presence of greater than 5 white blood cells per cubic millimeter in cerebrospinal fluid (CSF) with lymphoblasts present and/or clinical signs of CNS leukemia. If CSF leukemia is present subjects will have to receive intrathecal therapy and have documented negative CSF prior to enrolling.
* History or presence of clinically relevant CNS pathology (excluding headache) such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis or severe (≥ grade 3) CNS events including immune effector cell-associated neurotoxicity syndrome (ICANS) from prior chimeric antigen receptor T-cell (CAR T) or other T cell engager therapies.
* Isolated Extramedullary (EM) Disease.
* For Ph-IIM only: Current EM disease or presence of circulating leukemia blasts.
* Current autoimmune disease or history of autoimmune disease with potential CNS involvement.
* Active acute or chronic graft versus host disease requiring systemic treatment with immunosuppressive medication.
* Symptoms and/or signs that indicate an acute or uncontrolled chronic infection, any other disease or condition that could be exacerbated by the treatment or would complicate protocol compliance.
* Testicular leukemia.
* History of malignancy (with certain exceptions) other than ALL within 3 years prior to start of protocol-specified therapy.
* Allogeneic HSCT within 12 weeks before the start of protocol-specified therapy.
* Cancer chemotherapy within 2 weeks before the start of protocol-specified therapy (with certain exceptions).
* Immunotherapy within 4 weeks before start of protocol-specified therapy.
* Prior failed cluster of differentiation (CD19) directed therapy such as prior blinatumomab or CD19 CAR T cells will be allowed (with demonstrated continued CD19+ expression), if treatment ended more than 4 weeks prior to start of protocol therapy and no prior CNS complications.
* Currently receiving treatment in or less than 30 days or 5 half-lives since ending treatment on another investigational study(ies).
* Abnormal screening laboratory parameters.
* Female participant: Pregnant or breastfeeding or planning to become pregnant or donate eggs, or expected to breastfeed during treatment and for 96 hours after the last dose of investigational product (SC blinatumomab).
The above is a summary, other exclusion criteria details may apply.
Inclusion Criteria
Inclusion Criteria:
* Ph-IIC, Dose Escalation and Dose Expansion: Aged 18 years or older (or same or greater than legal age within the country if it is older than 18 years).
* Ph-IIRa and Ph-IIMa: Aged ≥ 17 years at time of informed consent.
* Ph-IIRb and Ph-IIMb: Age ≥ 12 years and \< 17 years at time of informed consent.
* Ph-IIR, Ph-IIC, Dose escalation, Dose Expansion: Participants with R/R B-precursor ALL.
* Relapsed or Refractory B-precursor ALL at any time after first salvage therapy.
* Relapsed B-precursor ALL at any time after allogenic hematopoietic stem cell transplant (HSCT).
* Ph-IIR, Ph-IIC, Dose escalation, Dose expansion: Greater than or equal to 5% blasts in the Bone Marrow per local assessment.
* Ph-IIM: B-precursor ALL and bone marrow blasts (BMB) ≥ 0.01% and \< 5% per local assessment.
* Ph-IIM: Availability of an appropriate archival BM specimen from initial or relapse diagnosis and the screening BM sample.
* Participants aged ≥ 18 years: Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2.
* Participants aged 16 to \< 18 years old: Karnofsky Performance Score ≥ 50%.
* Participants aged \< 16 years old: Lansky Performance Score ≥ 50%.
* Any Ph+ participant intolerant or refractory to prior tyrosine kinase inhibitors (TKIs) are eligible.
* Ph-IIM: BM function as follows:
* Absolute Neutrophil Count (ANC) ≥ 500/μL
* Platelet count ≥ 50 000/μL (transfusion permitted)
* Hemoglobin level ≥ 9 g/dL (transfusion permitted)
The above is a summary, other inclusion criteria details may apply.
* Ph-IIC, Dose Escalation and Dose Expansion: Aged 18 years or older (or same or greater than legal age within the country if it is older than 18 years).
* Ph-IIRa and Ph-IIMa: Aged ≥ 17 years at time of informed consent.
* Ph-IIRb and Ph-IIMb: Age ≥ 12 years and \< 17 years at time of informed consent.
* Ph-IIR, Ph-IIC, Dose escalation, Dose Expansion: Participants with R/R B-precursor ALL.
* Relapsed or Refractory B-precursor ALL at any time after first salvage therapy.
* Relapsed B-precursor ALL at any time after allogenic hematopoietic stem cell transplant (HSCT).
* Ph-IIR, Ph-IIC, Dose escalation, Dose expansion: Greater than or equal to 5% blasts in the Bone Marrow per local assessment.
* Ph-IIM: B-precursor ALL and bone marrow blasts (BMB) ≥ 0.01% and \< 5% per local assessment.
* Ph-IIM: Availability of an appropriate archival BM specimen from initial or relapse diagnosis and the screening BM sample.
* Participants aged ≥ 18 years: Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2.
* Participants aged 16 to \< 18 years old: Karnofsky Performance Score ≥ 50%.
* Participants aged \< 16 years old: Lansky Performance Score ≥ 50%.
* Any Ph+ participant intolerant or refractory to prior tyrosine kinase inhibitors (TKIs) are eligible.
* Ph-IIM: BM function as follows:
* Absolute Neutrophil Count (ANC) ≥ 500/μL
* Platelet count ≥ 50 000/μL (transfusion permitted)
* Hemoglobin level ≥ 9 g/dL (transfusion permitted)
The above is a summary, other inclusion criteria details may apply.
Gender
All
Gender Based
false
Keywords
R/R B-ALL
MRD+ B-ALL
Relapsed
Refractory
Minimal Residual Disease
AMG 103
Blinatumomab
Acute lymphoblastic leukemia
Adolescent
Adult
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
12 Years
NCT Id
NCT04521231
Org Class
Industry
Org Full Name
Amgen
Org Study Id
20180257
Overall Status
Recruiting
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Phase 1/2 Open-label Study to Investigate the Safety, Efficacy, and Pharmacokinetics of Administration of Subcutaneous Blinatumomab for the Treatment of Adults and Adolescents With Relapsed or Refractory B Cell Precursor Acute Lymphoblastic Leukemia (R/R B-ALL) and Minimal Residual Disease Positive (MRD+) B-ALL
Primary Outcomes
Outcome Measure
Dose Escalation Phase: Number of participants who experience dose limiting toxicities (DLTs)
Outcome Time Frame
Up to 29 days
Outcome Measure
Dose Escalation Phase: Number of participants who experience one or more treatment-emergent adverse events (TEAEs)
Outcome Time Frame
Up to approximately 28 weeks
Outcome Measure
Dose Escalation Phase: Number of participants who experience one or more serious TEAEs
Outcome Time Frame
Up to approximately 28 weeks
Outcome Measure
Dose Escalation Phase: Number of participants who experience one or more treatment-related TEAEs
Outcome Time Frame
Up to approximately 28 weeks
Outcome Measure
Dose Escalation Phase: Number of participants who experience one or more adverse events (AEs) of Interest (AEIs)
Outcome Time Frame
Up to approximately 28 weeks
Outcome Measure
Dose Expansion and Phase 2 Ph-IIR cohort: Number of participants who achieve complete remission (CR) / complete remission with partial hematological recovery (CRh)
Outcome Time Frame
Up to 10 weeks
Outcome Measure
Phase 2 Ph-IIC cohort: Maximum concentration (Cmax) of blinatumomab SC1 and SC2
Outcome Time Frame
Up to approximately 4 weeks
Outcome Measure
Phase 2 Ph-IIC cohort: Average concentration (Cavg) of blinatumomab SC1 and SC2
Outcome Time Frame
Up to approximately 4 weeks
Outcome Measure
Phase 2 Ph-IIC cohort: Time to reach maximum concentration (Tmax) of blinatumomab SC1 and SC2
Outcome Time Frame
Up to approximately 4 weeks
Outcome Measure
Phase 2 Ph-IIC cohort: Area under the concentration-time curve (AUC) of blinatumomab SC1 and SC2
Outcome Time Frame
Up to approximately 4 weeks
Outcome Measure
Phase 2 Ph-IIM cohort: Number of participants who achieve CR with MRD-negative response
Outcome Time Frame
Up to 10 weeks
Secondary Ids
Secondary Id
2023-506136-32
Secondary Outcomes
Outcome Time Frame
Up to approximately 10 weeks
Outcome Measure
Dose Escalation and Dose Expansion Phase: Minimum concentration over the dosing interval (Cmin) of blinatumomab
Outcome Time Frame
Up to approximately 10 weeks
Outcome Measure
Dose Escalation and Dose Expansion Phase: Cmax of blinatumomab
Outcome Time Frame
Up to approximately 10 weeks
Outcome Measure
Dose Escalation and Dose Expansion Phase: Tmax of blinatumomab
Outcome Time Frame
Up to approximately 10 weeks
Outcome Measure
Dose Escalation and Dose Expansion Phase: AUC of blinatumomab
Outcome Time Frame
Up to 10 weeks
Outcome Measure
Dose Escalation Phase and Phase 2 (Ph-IIC cohort): Number of participants who achieve CR/CRh
Outcome Time Frame
Up to approximately 28 weeks
Outcome Measure
Dose Escalation Phase, Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Number of participants with incidence of anti-blinatumomab antibody formation
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Overall survival (OS)
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Dose Expansion Phase and Phase 2 (Ph-IIR cohort and Ph-IIC cohort): Duration of response
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Relapse free survival
Outcome Time Frame
Up to approximately 28 weeks
Outcome Measure
Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Number of participants who experience one or more TEAEs
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Number of participants who experience one or more serious treatment-emergent adverse event
Outcome Time Frame
Up to approximately 28 weeks
Outcome Measure
Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Number of participants who experience one or more treatment-related treatment-emergent adverse events
Outcome Time Frame
Up to approximately 28 weeks
Outcome Measure
Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Number of participants who experience one or more AEIs
Outcome Description
The EORTC QLQ-C30 is defined as the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire.
Outcome Time Frame
Baseline (Day 1) up to approximately 28 weeks
Outcome Measure
Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Summary scores of quality of life at each assessment as assessed by the EORTC QLQ-C30 for participants aged ≥ 17 years at the time of consent
Outcome Time Frame
Baseline (Day 1) up to approximately 28 weeks
Outcome Measure
Dose Expansion Phase and Phase 2 (Ph-IIR cohort, Ph-IIM cohort and Ph-IIC cohort): Change from baseline of quality of life as assessed by the EORTC QLQ-C30 for participants aged ≥ 17 years at the time of consent
Outcome Time Frame
Baseline (Day 1) up to approximately 28 weeks
Outcome Measure
Phase 2 (Ph-IIR cohort and Ph-IIM cohort): Summary scores of quality of life at each assessment as assessed by PedsQL Generic Core Scale for participants aged 12 to < 17 years at time of consent
Outcome Time Frame
Baseline (Day 1) up to approximately 28 weeks
Outcome Measure
Phase 2 (Ph-IIR cohort and Ph-IIM cohort): Change from baseline of quality of life as assessed by PedsQL Generic Core Scale for participants aged 12 to < 17 years at time of consent
Outcome Time Frame
Up to 10 weeks
Outcome Measure
Phase 2 (Ph-IIR cohort): Number of participants who achieve CR
Outcome Time Frame
Up to 10 weeks
Outcome Measure
Phase 2 (Ph-IIR cohort): Number of participants who achieve CR, CRh, CRi (complete remission with incomplete hematological recovery) or blast free hypoplastic or aplastic bone marrow (BM)
Outcome Time Frame
Up to 10 weeks
Outcome Measure
Phase 2 (Ph-IIM cohort): Number of participants who achieve CR, CRh, CRi or blast free hypoplastic or aplastic BM with MRD-negative response
Outcome Time Frame
Up to 10 weeks
Outcome Measure
Phase 2 (Ph-IIR cohort and Ph-IIM cohort): Number of participants who achieve CR or CRh with MRD-negative response
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Phase 2 (Ph-IIR cohort and Ph-IIM cohort): Duration of molecular response
Outcome Time Frame
Up to approximately 4 weeks
Outcome Measure
Phase 2 (Ph-IIR cohort and Ph-IIM cohort): Cmax of blinatumomab for participants participating in intense PK sampling assessment
Outcome Time Frame
Up to approximately 4 weeks
Outcome Measure
Phase 2 (Ph-IIR cohort and Ph-IIM cohort): Tmax of blinatumomab for participants participating in intense PK sampling assessment
Outcome Time Frame
Up to approximately 4 weeks
Outcome Measure
Phase 2 (Ph-IIR cohort and Ph-IIM cohort): AUC of blinatumomab for participants participating in intense PK sampling assessment
Outcome Time Frame
Up to approximately 4 weeks
Outcome Measure
Phase 2 (Ph-IIR cohort and Ph-IIM cohort): Blinatumomab serum concentrations for participants not participating in intense PK sampling assessment
Outcome Description
This endpoint applies to participants aged ≥ 17 years at time of consent.
Outcome Time Frame
Baseline (Day 1) up to approximately 28 weeks
Outcome Measure
Phase 2 (Ph-IIR cohort and Ph-IIM cohort): Proportion of time on treatment with high side effect bother from baseline to end of treatment as measured by Functional Assessment of Chronic Illness Therapy (FACIT) GP5 item for participants aged ≥ 17 years
Outcome Time Frame
Up to approximately 28 weeks
Outcome Measure
Phase 2 (Ph-IIR cohort and Ph-IIM cohort): Pain difference between pain score before and after injection as reported using the Numeric Rating Scale (NRS-11) for participants aged 12 to < 17 years at time of consent
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
12
Investigators
Investigator Type
Principal Investigator
Investigator Name
Ioannis Mantzaris
Investigator Email
IMANTZAR@montefiore.org
Investigator Department
Medicine
Investigator Division
Oncology
Investigator Sponsor Organization
External
Study Department
Oncology (Medical/Hematologic)
Study Division
Medical and Hematologic Oncology
Categories Mesh Debug
Blood & Bone Marrow Cancers --- PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA
Cancer --- NEOPLASMS
Blood & Bone Marrow Cancers --- LEUKEMIA, LYMPHOID
Cancer --- LEUKEMIA
Blood & Bone Marrow Cancers --- LEUKEMIA
Blood Disorders --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- HEMATOLOGIC DISEASES
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
RECURRENCE
NEOPLASM, RESIDUAL
PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA
DISEASE ATTRIBUTES
PATHOLOGIC PROCESSES
PATHOLOGICAL CONDITIONS, SIGNS AND SYMPTOMS
NEOPLASTIC PROCESSES
NEOPLASMS
LEUKEMIA, LYMPHOID
LEUKEMIA
NEOPLASMS BY HISTOLOGIC TYPE
HEMATOLOGIC DISEASES
HEMIC AND LYMPHATIC DISEASES
LYMPHOPROLIFERATIVE DISORDERS
LYMPHATIC DISEASES
IMMUNOPROLIFERATIVE DISORDERS
IMMUNE SYSTEM DISEASES
BLINATUMOMAB