AzTrials
AzTrials

Acute Lymphoblastic LeukemiaPhase 1NCT01324180

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

A Phase 1 study testing Metformin, Vincristine and Dexamethasone in people with Acute Lymphoblastic Leukemia, run by H. Lee Moffitt Cancer Center and Research Institute at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 1 year to 30 years
Conditions the study is for
Acute Lymphoblastic Leukemia
What is being tested?
Metformin, Vincristine and Dexamethasone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
5 sitesUnited States
Study dates
18 Jul 2011to 27 Jul 2017
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 30 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.
Show all 12Show fewer
  • 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.

Who cannot join

  • 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.
Show all 15Show fewer
  • 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.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

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

    Miami, Florida, 33136

  • Arnold Palmer Hospital for Children

    Orlando, Florida, 32806

  • All Children's Hospital

    St. Petersburg, Florida, 33701

  • Montefiore Medical Center, The Children's Hospital at Montefiore

    The Bronx, New York, 10467

Other trials in United States

About this study

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)

  1. 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.

Read the 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.

Being tested
Metformin, Vincristine, Dexamethasone, PEG-asparaginase, Doxorubicin
Keywords
ALL, Relapsed, Refractory
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MetforminDrug

    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.

  • VincristineDrug

    Also called Oncovin®, VCR, LCR, NSC #67574

    1.5 mg/m^2/dose IV push (maximum single dose 2 mg) on days 2, 9, 16 and 23

  • DexamethasoneDrug

    Also called Decadron®, Hexadrol®, Dexone®, Dexameth®

    • 10 mg/m^2/day divided BID
    • Take dexamethasone by mouth days 2-15

  • PEG-asparaginaseDrug

    Also called Oncaspar, NSC #644954, Pegaspargase, Oncaspar®

    • 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.

  • DoxorubicinDrug

    Also called Adriamycin®, NSC #123127 (102004)

    60 mg/m^2/day IV over 15 minutes on day 2

  • Intrathecal chemotherapyDrug

    Also called Cytosine Arabinoside, Ara-C, Cytosar®, NSC #63878 (102004)

    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.
Study groups in NCT01324180
Study groupRoleWhat they receive
VLPD RegimenExperimentalInduction 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.
Receives: Drug: Metformin; Drug: Vincristine; Drug: Dexamethasone; Drug: PEG-asparaginase; Drug: Doxorubicin; Drug: Intrathecal chemotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD)

    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.

    Measured: 45 days

Secondary outcomes (3)

  1. The Number of Participants with Complete Remission

    Patients who have:

    • No evidence of circulating blasts or extramedullary disease;
    • A bone marrow with <5% blasts (M1 marrow); and
    • Recovery of peripheral counts (platelets ≥75,000 and absolute neutrophil count (ANC) ≥750)
    • Qualifying marrow and peripheral counts should be performed within 1 week of each other

    Measured: 45 days

  2. The Number of Participants with Biological Response to Treatment

    To evaluate the biological response of ALL blasts from children receiving metformin in a window fashion and in later time points.

    Measured: 45 days

  3. The Number of Participants with Adverse Events as a Measure of Safety and Feasibility

    To demonstrate the safety and feasibility of the addition of metformin to induction chemotherapy for recurrent ALL.

    Measured: 45 Days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Mar 2011 (estimated)
  2. Study start18 Jul 2011
  3. Primary completion16 Nov 2016
  4. Study completion27 Jul 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01324180
Sponsor's protocol ID
MCC-16601
Other IDs
Sunshine Project 001
Status last verified
Aug 2017
First submitted
24 Mar 2011
Last updated
7 Aug 2017
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Metformin, Vincristine and Dexamethasone in people with Acute Lymphoblastic Leukemia, run by H. Lee Moffitt Cancer Center and Research Institute at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) (time frame: 45 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01324180.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in