Brief Summary
H. Lee Moffitt Cancer Center and Research Institute will be the Sunshine Project Coordinator, but will not be recruiting locally.
The purpose of the trial is to study the clinical and biological effects of metformin in combination with standard systemic chemotherapy in a disease (relapsed ALL) that has a dismal outcome, as well as to do a dose escalation study to find the Maximum Tolerated Dose (MTD) of metformin in conjunction with ALL therapy. There have also been analysis of patients enrolled on trials who were diabetics on metformin and their outcome was better than patients on the same trial that were not on metformin as their antihyperglycemic.
The purpose of the trial is to study the clinical and biological effects of metformin in combination with standard systemic chemotherapy in a disease (relapsed ALL) that has a dismal outcome, as well as to do a dose escalation study to find the Maximum Tolerated Dose (MTD) of metformin in conjunction with ALL therapy. There have also been analysis of patients enrolled on trials who were diabetics on metformin and their outcome was better than patients on the same trial that were not on metformin as their antihyperglycemic.
Brief Title
Vincristine, Dexamethasone, Doxorubicin, and PEG-asparaginase (VPLD) and Metformin for Relapsed Childhood Acute Lymphoblastic Leukemia (ALL)
Detailed Description
This will be a phase I protocol of Vincristine, Dexamethasone, Doxorubicin, and PEG-asparaginase (VPLD) and metformin conducted in the Sunshine Project sites for children with recurrent ALL. All sites will be eligible to open this study, provided they agree to adhere to all study procedures and make a good faith effort to obtain all pharmacodynamic and pharmacokinetic evaluations requested.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Acute Lymphoblastic Leukemia
Eligibility Criteria
Inclusion Criteria:
* ALL or lymphoblastic lymphoma patients in first or higher relapse.
* Male or Female age 1-30 years at initial diagnosis.
* Signed informed consent.
* Karnofsky / Lansky score above 50%.
* No known contraindications to intended therapies.
* Prior anthracycline exposure: Patients must have had less than 350 mg/m\^2 lifetime exposure of anthracycline chemotherapy.
* It must be at least 6 months since the last treatment with a "VPLD" induction/re-induction type regimen (i.e. anthracycline, steroid, asparaginase and vincristine).
* Patients must have adequate organ function.
* Adequate renal function defined as serum creatinine \< 1.5 x upper limit of normal (ULN) for age.
* Total bilirubin \< 1.5 X ULN for age.
* Alanine transaminase (ALT) \< 5 X ULN for age, unless the elevation is disease-related.
* Adequate cardiac function as defined as shortening fraction of \> 27% by echocardiogram or ejection fraction \> 45% by gated radionuclide study.
Exclusion Criteria:
* Significant renal impairment as determined per investigator discretion.
* Patients planning on receiving other investigational agents while on this study.
* Patients planning on receiving other anti-cancer therapies while on this study.
* Patients with active infection defined as: positive blood culture within 48 hours of study registration; need for supplemental oxygen or vasopressors within 48 hours of study entry.
* Patient receiving corticosteroids, aside from dexamethasone treatment directed at leukemia.
* Known intolerance to doxorubicin, metformin, or vincristine.
* Patients who have started protocol therapy prior to enrollment. Patient may still enroll if IT therapy was given within 72 hours of study enrollment as part of the diagnostic lumbar procedure.
* Patients may be on hydroxurea until the first dose of metformin is to be given.
* Patients who have a need to continue hydroxurea while on study (Patients may continue on hydroxurea only until the first dose of metformin is to given).
* Patients with creatinine more than 1.5 x the ULN
* Patients must have recovered from the acute side effects of all prior anticancer therapy.
* At least 1 week from prior cytotoxic chemotherapy.
* At least 4 weeks from craniospinal irradiation.
* At least 4 months since hematopoietic stem cell transplant (HSCT) with no evidence of active graft-versus-host disease (GVHD).
* Pregnant or lactating women.
* ALL or lymphoblastic lymphoma patients in first or higher relapse.
* Male or Female age 1-30 years at initial diagnosis.
* Signed informed consent.
* Karnofsky / Lansky score above 50%.
* No known contraindications to intended therapies.
* Prior anthracycline exposure: Patients must have had less than 350 mg/m\^2 lifetime exposure of anthracycline chemotherapy.
* It must be at least 6 months since the last treatment with a "VPLD" induction/re-induction type regimen (i.e. anthracycline, steroid, asparaginase and vincristine).
* Patients must have adequate organ function.
* Adequate renal function defined as serum creatinine \< 1.5 x upper limit of normal (ULN) for age.
* Total bilirubin \< 1.5 X ULN for age.
* Alanine transaminase (ALT) \< 5 X ULN for age, unless the elevation is disease-related.
* Adequate cardiac function as defined as shortening fraction of \> 27% by echocardiogram or ejection fraction \> 45% by gated radionuclide study.
Exclusion Criteria:
* Significant renal impairment as determined per investigator discretion.
* Patients planning on receiving other investigational agents while on this study.
* Patients planning on receiving other anti-cancer therapies while on this study.
* Patients with active infection defined as: positive blood culture within 48 hours of study registration; need for supplemental oxygen or vasopressors within 48 hours of study entry.
* Patient receiving corticosteroids, aside from dexamethasone treatment directed at leukemia.
* Known intolerance to doxorubicin, metformin, or vincristine.
* Patients who have started protocol therapy prior to enrollment. Patient may still enroll if IT therapy was given within 72 hours of study enrollment as part of the diagnostic lumbar procedure.
* Patients may be on hydroxurea until the first dose of metformin is to be given.
* Patients who have a need to continue hydroxurea while on study (Patients may continue on hydroxurea only until the first dose of metformin is to given).
* Patients with creatinine more than 1.5 x the ULN
* Patients must have recovered from the acute side effects of all prior anticancer therapy.
* At least 1 week from prior cytotoxic chemotherapy.
* At least 4 weeks from craniospinal irradiation.
* At least 4 months since hematopoietic stem cell transplant (HSCT) with no evidence of active graft-versus-host disease (GVHD).
* Pregnant or lactating women.
Inclusion Criteria
Inclusion Criteria:
* ALL or lymphoblastic lymphoma patients in first or higher relapse.
* Male or Female age 1-30 years at initial diagnosis.
* Signed informed consent.
* Karnofsky / Lansky score above 50%.
* No known contraindications to intended therapies.
* Prior anthracycline exposure: Patients must have had less than 350 mg/m\^2 lifetime exposure of anthracycline chemotherapy.
* It must be at least 6 months since the last treatment with a "VPLD" induction/re-induction type regimen (i.e. anthracycline, steroid, asparaginase and vincristine).
* Patients must have adequate organ function.
* Adequate renal function defined as serum creatinine \< 1.5 x upper limit of normal (ULN) for age.
* Total bilirubin \< 1.5 X ULN for age.
* Alanine transaminase (ALT) \< 5 X ULN for age, unless the elevation is disease-related.
* Adequate cardiac function as defined as shortening fraction of \> 27% by echocardiogram or ejection fraction \> 45% by gated radionuclide study.
* ALL or lymphoblastic lymphoma patients in first or higher relapse.
* Male or Female age 1-30 years at initial diagnosis.
* Signed informed consent.
* Karnofsky / Lansky score above 50%.
* No known contraindications to intended therapies.
* Prior anthracycline exposure: Patients must have had less than 350 mg/m\^2 lifetime exposure of anthracycline chemotherapy.
* It must be at least 6 months since the last treatment with a "VPLD" induction/re-induction type regimen (i.e. anthracycline, steroid, asparaginase and vincristine).
* Patients must have adequate organ function.
* Adequate renal function defined as serum creatinine \< 1.5 x upper limit of normal (ULN) for age.
* Total bilirubin \< 1.5 X ULN for age.
* Alanine transaminase (ALT) \< 5 X ULN for age, unless the elevation is disease-related.
* Adequate cardiac function as defined as shortening fraction of \> 27% by echocardiogram or ejection fraction \> 45% by gated radionuclide study.
Gender
All
Gender Based
false
Keywords
ALL
Relapsed
Refractory
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
30 Years
Minimum Age
1 Year
NCT Id
NCT01324180
Org Class
Other
Org Full Name
H. Lee Moffitt Cancer Center and Research Institute
Org Study Id
MCC-16601
Overall Status
Completed
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase I Window, Dose Escalating and Safety Trial of Metformin in Combination With Induction Chemotherapy in Relapsed Refractory Acute Lymphoblastic Leukemia: Metformin With Induction Chemotherapy of Vincristine, Dexamethasone, Doxorubicin, and PEG-asparaginase (VPLD)
Primary Outcomes
Outcome Description
MTD determined by Dose Limiting Toxicity (DLT), any time during the first course of therapy. Dose Limiting Toxicities: Any Grade 3 or 4 non-hematological toxicity by Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0 felt to be probably or definitely related to the study agent, persistent marrow aplasia at day 44, lactic acidosis for grade 3 or 4, grade 3 and 4 hypoglycemia.
Outcome Measure
Maximum Tolerated Dose (MTD)
Outcome Time Frame
45 days
Secondary Ids
Secondary Id
Sunshine Project 001
Secondary Outcomes
Outcome Description
Patients who have:
* No evidence of circulating blasts or extramedullary disease;
* A bone marrow with \<5% blasts (M1 marrow); and
* Recovery of peripheral counts (platelets ≥75,000 and absolute neutrophil count (ANC) ≥750)
* Qualifying marrow and peripheral counts should be performed within 1 week of each other
* No evidence of circulating blasts or extramedullary disease;
* A bone marrow with \<5% blasts (M1 marrow); and
* Recovery of peripheral counts (platelets ≥75,000 and absolute neutrophil count (ANC) ≥750)
* Qualifying marrow and peripheral counts should be performed within 1 week of each other
Outcome Time Frame
45 days
Outcome Measure
The Number of Participants with Complete Remission
Outcome Description
To evaluate the biological response of ALL blasts from children receiving metformin in a window fashion and in later time points.
Outcome Time Frame
45 days
Outcome Measure
The Number of Participants with Biological Response to Treatment
Outcome Description
To demonstrate the safety and feasibility of the addition of metformin to induction chemotherapy for recurrent ALL.
Outcome Time Frame
45 Days
Outcome Measure
The Number of Participants with Adverse Events as a Measure of Safety and Feasibility
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
Daniel Weiser
Investigator Email
daniel.weiser@einsteinmed.org
Investigator Phone
718-741-2334
Categories Mesh Debug
Blood & Bone Marrow Cancers --- PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA
Blood & Bone Marrow Cancers --- LEUKEMIA, LYMPHOID
Cancer --- LEUKEMIA
Blood & Bone Marrow Cancers --- LEUKEMIA
Cancer --- NEOPLASMS
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
PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA
RECURRENCE
LEUKEMIA, LYMPHOID
LEUKEMIA
NEOPLASMS BY HISTOLOGIC TYPE
NEOPLASMS
HEMATOLOGIC DISEASES
HEMIC AND LYMPHATIC DISEASES
LYMPHOPROLIFERATIVE DISORDERS
LYMPHATIC DISEASES
IMMUNOPROLIFERATIVE DISORDERS
IMMUNE SYSTEM DISEASES
DISEASE ATTRIBUTES
PATHOLOGIC PROCESSES
PATHOLOGICAL CONDITIONS, SIGNS AND SYMPTOMS
METFORMIN
VINCRISTINE
DEXAMETHASONE
CALCIUM DOBESILATE
PEGASPARGASE
POLYETHYLENE
DOXORUBICIN
CYTARABINE
BIGUANIDES
GUANIDINES
AMIDINES
ORGANIC CHEMICALS
VINCA ALKALOIDS
SECOLOGANIN TRYPTAMINE ALKALOIDS
INDOLE ALKALOIDS
ALKALOIDS
HETEROCYCLIC COMPOUNDS
INDOLES
HETEROCYCLIC COMPOUNDS, 2-RING
HETEROCYCLIC COMPOUNDS, FUSED-RING
INDOLIZIDINES
INDOLIZINES
PREGNADIENETRIOLS
PREGNADIENES
PREGNANES
STEROIDS
FUSED-RING COMPOUNDS
POLYCYCLIC COMPOUNDS
STEROIDS, FLUORINATED
BENZENESULFONATES
BENZENE DERIVATIVES
HYDROCARBONS, AROMATIC
HYDROCARBONS, CYCLIC
HYDROCARBONS
ARYLSULFONATES
ARYLSULFONIC ACIDS
SULFONIC ACIDS
SULFUR ACIDS
SULFUR COMPOUNDS
POLYETHYLENES
POLYENES
ALKENES
HYDROCARBONS, ACYCLIC
PLASTICS
POLYMERS
MACROMOLECULAR SUBSTANCES
BIOMEDICAL AND DENTAL MATERIALS
MANUFACTURED MATERIALS
TECHNOLOGY, INDUSTRY, AND AGRICULTURE
DAUNORUBICIN
ANTHRACYCLINES
NAPHTHACENES
POLYCYCLIC AROMATIC HYDROCARBONS
AMINOGLYCOSIDES
GLYCOSIDES
CARBOHYDRATES
CYTIDINE
PYRIMIDINE NUCLEOSIDES
PYRIMIDINES
HETEROCYCLIC COMPOUNDS, 1-RING
ARABINONUCLEOSIDES
NUCLEOSIDES
NUCLEIC ACIDS, NUCLEOTIDES, AND NUCLEOSIDES