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

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.

Conditions

• Acute Lymphoblastic Leukemia

Interventions

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.

Sponsors & Collaborators

• Pediatric Cancer Foundation

  collaborator OTHER

• H. Lee Moffitt Cancer Center and Research Institute

  lead OTHER

Principal Investigators

• Julio M. Barredo, M.D. · Holtz Children's Hospital University of Miami Miller School of Medicine

• Damon Reed, M.D. · H. Lee Moffitt Cancer Center and Research Institute

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

1 Year

Max Age

30 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-07-18

Primary Completion

2016-11-16

Completion

2017-07-27

FDA Drug

Yes

Countries

• United States

Study Locations