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Trial record 39 of 48 for:    "Acute Lymphoblastic Leukemia, Childhood" | "Pegaspargase"

Pre-reinductive Decitabine and Vorinostat in Relapsed Lymphoblastic Lymphoma or Acute Lymphoblastic Leukemia

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ClinicalTrials.gov Identifier: NCT00882206
Recruitment Status : Terminated (Slow accrual)
First Posted : April 16, 2009
Results First Posted : October 28, 2016
Last Update Posted : December 28, 2017
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Tracking Information
First Submitted Date  ICMJE April 15, 2009
First Posted Date  ICMJE April 16, 2009
Results First Submitted Date  ICMJE April 10, 2015
Results First Posted Date  ICMJE October 28, 2016
Last Update Posted Date December 28, 2017
Study Start Date  ICMJE April 2009
Actual Primary Completion Date January 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 8, 2016)
Response to Treatment [ Time Frame: Day 33 ]
Response includes both complete remission (defined as <5% leukemic blasts in the bone marrow) and partial remission (defined as a greater than 35% reduction in the bone marrow leukemia blast percentage at day 33)
Original Primary Outcome Measures  ICMJE
 (submitted: April 15, 2009)
Efficacy as measured by remission rate at day 33 (< 5% blasts) or day 42 per RECIST criteria
Change History Complete list of historical versions of study NCT00882206 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 1, 2017)
  • Level of Methylation [ Time Frame: Day 0 ]
    the percentage of methylated DNA
  • Level of Methylation [ Time Frame: Day 5 ]
    the percentage of methylated DNA
  • Level of Methylation [ Time Frame: Day 33 ]
    the percentage of methylated DNA
Original Secondary Outcome Measures  ICMJE
 (submitted: April 15, 2009)
  • Toxicity as measured by NCI CTCAE v3.0
  • Biological correlative endpoints at baseline, on day 5, and at the end of study treatment
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pre-reinductive Decitabine and Vorinostat in Relapsed Lymphoblastic Lymphoma or Acute Lymphoblastic Leukemia
Official Title  ICMJE A Therapeutic Trial of Decitabine and Vorinostat in Combination With Chemotherapy (Vincristine, Prednisone, Doxorubicin and PEG-Asparaginase) for Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LL)
Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Decitabine and vorinostat may alter the cancer cells by reversing the cancer pathways needed for cell growth. Giving more than one drug (combination chemotherapy) together with decitabine and vorinostat may kill more cancer cells than with chemotherapy alone.

PURPOSE: This phase II trial is studying how well giving decitabine and vorinostat together with combination chemotherapy works in treating patients with acute lymphoblastic leukemia or lymphoblastic lymphoma that has relapsed or not responded to treatment.

Detailed Description

OBJECTIVES:

Primary

  • Patients undergo blood and bone marrow sample collection at baseline, on day 5, Day 19 and at the end of study treatment for correlative laboratory studies. Samples are analyzed for hypermethylation at diagnosis and demethylation post-exposure with decitabine and vorinostat using LINE methylation.

OUTLINE:

Patients receive decitabine IV over 1 hour and oral vorinostat twice daily on days 1-4; vincristine sulfate IV on days 5, 12, 19, and 26; oral prednisone twice daily on days 5-33; doxorubicin hydrochloride IV over 15 minutes and cytarabine intrathecally (IT) on day 5; pegaspargase IV or intramuscularly on days 6, 12, 19, and 26; and methotrexate* IT on days 12 and 33. Patients with Philadelphia chromosome-positive disease may also receive oral imatinib mesylate once daily on days 5-33.

NOTE: *Patients with central nervous system (CNS)-positive disease also receive methotrexate IT on days 19 and 26.

Patients undergo blood and bone marrow sample collection at baseline, on day 5, Day 19 and at the end of study treatment for correlative laboratory studies.

After completion of study treatment, patients are followed for 60 days.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Leukemia
  • Lymphoma
Intervention  ICMJE
  • Drug: cytarabine

    At baseline when peripheral blood draw and bone marrow aspirate performed.

    *Intrathecal Cytarabine administered dependent upon age - ranging from 30 mg to 70 mg.

    Other Name: cytosine arabinoside
  • Drug: decitabine
    Days 1-4, 15 mg/m^2 intravenously (IV) over 1 hour
    Other Name: Dacogen(R)
  • Drug: doxorubicin hydrochloride
    Day 5, 60 mg/m^2 intravenously (IV) over 15 minutes
    Other Name: Doxorubicin
  • Drug: imatinib mesylate
    340 mg/m2 by mouth every day (rounded to the nearest 100 mg) for age <18 years and 400 mg orally every day for >18 years on Days 5-33.
    Other Name: Gleevec(R)
  • Drug: methotrexate
    **Intrathecal Methotrexate administered dependent upon age - ranging from 8 mg to 15 mg.
    Other Name: MTX
  • Drug: pegaspargase
    2,500 IU/m2 IM or IV q week (days 6, 12, 19, 26)
    Other Name: PEG asparaginase
  • Drug: prednisone
    40mg/m2/day divided BID (days 5 - 33)
  • Drug: vincristine sulfate
    1.5mg/m2 (max 2 mg) iv push q week (days 5, 12, 19, 26)
    Other Name: Oncovin(R)
  • Drug: vorinostat
    Days 1-4, (230 mg/m2)orally divided twice a day (max dose 400 mg daily)
    Other Name: suberoylanilide hydroxamic acid (SAHA)
Study Arms  ICMJE Experimental: Decitabine / Vorinostat
This is a therapeutic trial investigating the combination of decitabine 15 mg/m2 and vorinostat 230 mg/m2 (maximum daily dose not to exceed 400 mg) in relapsed/refractory ALL/LL patients prior to induction chemotherapy.
Interventions:
  • Drug: cytarabine
  • Drug: decitabine
  • Drug: doxorubicin hydrochloride
  • Drug: imatinib mesylate
  • Drug: methotrexate
  • Drug: pegaspargase
  • Drug: prednisone
  • Drug: vincristine sulfate
  • Drug: vorinostat
Publications * Burke MJ, Lamba JK, Pounds S, Cao X, Ghodke-Puranik Y, Lindgren BR, Weigel BJ, Verneris MR, Miller JS. A therapeutic trial of decitabine and vorinostat in combination with chemotherapy for relapsed/refractory acute lymphoblastic leukemia. Am J Hematol. 2014 Sep;89(9):889-95. doi: 10.1002/ajh.23778. Epub 2014 Jun 27.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: September 8, 2016)
15
Original Estimated Enrollment  ICMJE
 (submitted: April 15, 2009)
40
Actual Study Completion Date  ICMJE January 2013
Actual Primary Completion Date January 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of lymphoblastic lymphoma or acute lymphoblastic leukemia with ≥ 5% blasts in the bone marrow (M2/M3) (with or without extramedullary disease) that meets 1 of the following criteria:

    • Refractory disease/induction failure (failure to achieve initial remission after 2 lines of induction therapy)
    • Relapsed disease (in first relapse or higher)
  • Central nervous system (CNS)-positive disease allowed
  • Karnofsky performance status (PS) 50-100% (for patients ≥ 16 years of age) OR Lansky PS 50-100% (for patients < 16 years of age)
  • Life expectancy ≥ 8 weeks
  • Creatinine clearance ≥ 70 mL/min OR maximum serum creatinine based on age/gender as follows:

    • 0.4 mg/dL (for patients 1 to 5 months of age)
    • 0.5 mg/dL (for patients 6 to 11 months of age)
    • 0.6 mg/dL (for patients 1 year of age)
    • 0.8 mg/dL (for patients 2 to 5 years of age)
    • 1.0 mg/dL (for patients 6 to 9 years of age)
    • 1.2 mg/dL (for patients 10 to 12 years of age)
    • 1.5 mg/dL (males) or 1.4 mg/dL (females) (for patients 13 to 15 years of age)
    • 1.7 mg/dL (males) or 1.4 mg/dL (females) (for patients ≥ 16 years of age)
  • ALT < 5 times upper limit of normal (ULN)
  • Total bilirubin ≤ 1.5 times ULN for age
  • LVEF ≥ 40% by ECHO/MUGA scan
  • Shortening fraction > 29% by ECHO/MUGA scan
  • Able to swallow capsules
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 2 months after completion of study treatment
  • No untreated positive blood cultures or progressive infections as assessed by radiographic studies
  • No known allergy to any of the agents or their ingredients used in this study

    • Patients with clinically significant prior allergies to pegaspargase may be treated with asparaginase-Erwinia, if available
  • Patients who cannot receive asparaginase on this study (e.g., due to prior pancreatitis, stroke, or other toxicity) are eligible provided they meet all other inclusion/exclusion criteria
  • Recovered from prior therapy (defined as CTCAE v3.0 toxicity ≤ grade 1)
  • More than 3 weeks since prior chemotherapy for cancer other than hydroxyurea for patients with WBC > 10,000/mm³
  • At least 7 days since prior hematopoietic growth factors (14 days for pegfilgrastim)
  • At least 1 month since prior biologic therapy, such as monoclonal antibodies
  • At least 3 months since prior hematopoietic stem cell transplantation

Exclusion Criteria:

  • Evidence of graft-versus-host disease
  • Concurrent valproic acid
  • Concurrent coumadin/warfarin other than a short course administered in a prophylactic setting
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 60 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00882206
Other Study ID Numbers  ICMJE 2008LS112
0810M50401 ( Other Identifier: IRB, University of Minnesota )
MT2008-29R ( Other Identifier: Blood and Marrow Transplantation Program )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Masonic Cancer Center, University of Minnesota
Study Sponsor  ICMJE Masonic Cancer Center, University of Minnesota
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Michael J. Burke, MD Masonic Cancer Center, University of Minnesota
PRS Account Masonic Cancer Center, University of Minnesota
Verification Date December 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP