Vincristine, Dexamethasone, Doxorubicin, and PEG-asparaginase (VPLD) and Metformin for Relapsed Childhood Acute Lymphoblastic Leukemia (ALL)
Acute Lymphoblastic Leukemia
About this trial
This is an interventional treatment trial for Acute Lymphoblastic Leukemia focused on measuring ALL, Relapsed, Refractory
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.
Sites / Locations
- Holtz Children's Hospital University of Miami Miller School of Medicine
- Arnold Palmer Hospital for Children
- All Children's Hospital
- Montefiore Medical Center, The Children's Hospital at Montefiore
- Nationwide Children's Hospital
Arms of the Study
Arm 1
Experimental
VLPD Regimen
Induction will consist of vincristine, dexamethasone, doxorubicin and PEG asparaginase (so called VPLD - dexamethasone is substituted for prednisone and PEG asparaginase is substituted for L-asparaginase) in combination with metformin. Eligible patients will receive 24 hours of metformin followed by induction. Intrathecal chemotherapy with standard dose cytarabine will be administered at the start of each cycle, with central nervous system (CNS) therapy afterwards determined by findings on staging lumbar puncture.