Clinical trial NCT01324180: Vincristine, Dexamethasone, Doxorubicin, and PEG-asparaginase (VPLD) and Metformin for Relapsed Childhood Acute Lymphoblastic Leukemia (ALL)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Lymphoblastic Leukemia
Keywords: ALL
Relapsed
Refractory
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: Pediatric Cancer Foundation
First posted: 2011-03-28
Enrollment: 14
Sex: ALL
Minimum age (years): 1
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: 45 days
Secondary outcomes:
measure: The Number of Participants with Complete Remission
timeFrame: 45 days
measure: The Number of Participants with Biological Response to Treatment
timeFrame: 45 days
measure: The Number of Participants with Adverse Events as a Measure of Safety and Feasibility
timeFrame: 45 Days
Other outcomes:
Locations:
city: Miami
country: United States
facility: Holtz Children's Hospital University of Miami Miller School of Medicine
state: Florida
city: Orlando
country: United States
facility: Arnold Palmer Hospital for Children
state: Florida
city: Saint Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: The Bronx
country: United States
facility: Montefiore Medical Center, The Children's Hospital at Montefiore
state: New York
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
Study officials:
affiliation: Holtz Children's Hospital University of Miami Miller School of Medicine
name: Julio M. Barredo, M.D.
role: STUDY_CHAIR
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Damon Reed, M.D.
role: PRINCIPAL_INVESTIGATOR
References: