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

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Brief Title

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)

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.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Maximum Tolerated Dose (MTD)

Secondary Outcome

 The Number of Participants with Complete Remission

Condition

Acute Lymphoblastic Leukemia

Intervention

Metformin

Study Arms / Comparison Groups

 VLPD Regimen
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

14

Start Date

July 18, 2011

Completion Date

July 27, 2017

Primary Completion Date

November 16, 2016

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.
      

Gender

All

Ages

1 Year - 30 Years

Accepts Healthy Volunteers

No

Contacts

Julio M. Barredo, M.D., , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01324180

Organization ID

MCC-16601

Secondary IDs

Sunshine Project 001

Responsible Party

Sponsor

Study Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Collaborators

 Pediatric Cancer Foundation

Study Sponsor

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


Verification Date

August 2017