NCT01324180

Vincristine, Dexamethasone, Doxorubicin, and PEG-asparaginase (VPLD) and Metformin for Relapsed Childhood Acute Lymphoblastic Leukemia (ALL)

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)

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 14 (actual)
• Sponsor: H. Lee Moffitt Cancer Center and Research Institute · Academic / Other
• Sex: All
• Age: 1 Year – 30 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Acute Lymphoblastic Leukemia

Interventions

Type	Name	Description
DRUG	Metformin	Will be dosed orally BID as per dose level of subject as defined in dose escalation schema. Both liquid and tablet forms are allowed and can be chosen based on convenience. Metformin will be continued throughout the cycle until Day 28 or until the patient is removed from study (e.g. to pursue new lines of therapy such as transplant), whichever occurs sooner.
DRUG	Vincristine	1.5 mg/m\^2/dose IV push (maximum single dose 2 mg) on days 2, 9, 16 and 23
DRUG	Dexamethasone	* 10 mg/m\^2/day divided BID * Take dexamethasone by mouth days 2-15
DRUG	PEG-asparaginase	* 2500 IU's/m\^2/day * Intramuscular injection (IM) or intravenous infusion per institutional standard on days 3, 9, 16 and 23 * If the patient develops an allergic reaction to PEG while being treated on this protocol, eliminate all future doses of PEG and substitute Erwinia if not intolerant of Erwinia and has no history of pancreatitis. * Patients will receive Erwinase® 25,000 IU/m\^2 x 6 doses intramuscularly (IM) on a Monday/Wednesday/Friday schedule as a replacement for each scheduled dose of PEG-asparaginase on the original protocol.
DRUG	Doxorubicin	60 mg/m\^2/day IV over 15 minutes on day 2
DRUG	Intrathecal chemotherapy	IT cytarabine given intrathecally to all patients on day 1 of each cycle. Dose defined by age. May be given with staging lumbar puncture before enrollment, but must be within 72 hours of starting therapy. If not done at study entry or before, may be done on Day 2 prior to doxorubicin administration. * 30 mg for patients age 1-1.99 * 50 mg for patients age 2-2.99 * 70 mg for patients greater than 3 years of age IT methotrexate given Intrathecally to all patients who are CNS negative at study entry on day 16 at the dose defined by age.

Timeline

• Start date: 2011-07-18
• Primary completion: 2016-11-16
• Completion: 2017-07-27
• First posted: 2011-03-28
• Last updated: 2017-08-07

Locations

5 sites across 1 country: United States

Regulatory

• FDA-regulated drug study