Know Cancer

or
forgot password

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)


Phase 1
1 Year
30 Years
Open (Enrolling)
Both
Acute Lymphoblastic Leukemia

Thank you

Trial Information

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)


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.


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) < 5X 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.

- 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.

- No corticosteroids allowed aside from dexamethasone treatment directed at leukemia.

- Patients who are allergic to PEG-asparaginase or who cannot tolerate any
asparaginase, either because of history of pancreatitis or allergy, will go on study
without asparaginase.

- 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 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.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose (MTD)

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 Time Frame:

45 days

Safety Issue:

No

Principal Investigator

John M. Goldberg, M.D.

Investigator Role:

Study Chair

Investigator Affiliation:

Holtz Children's Hospital University of Miami Miller School of Medicine

Authority:

United States: Food and Drug Administration

Study ID:

MCC-16601

NCT ID:

NCT01324180

Start Date:

March 2011

Completion Date:

March 2014

Related Keywords:

  • Acute Lymphoblastic Leukemia
  • ALL
  • Relapsed
  • Refractory
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma

Name

Location

Nemours Children's ClinicJacksonville, Florida  32207
All Children's HospitalSt. Petersburg, Florida  33701
University of Florida Shands Cancer CenterGainesville, Florida  32610-0232
M.D. Anderson of OrlandoOrlando, Florida  32806
Holtz Children's Hospital University of Miami Miller School of MedicineMiami, Florida  33136
Montefiore Medical Center, The Children's Hospital at MontefioreBronx, New York  10467