Decitabine, Vorinostat, and Combination Chemotherapy in Treating Patients With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma That Has Relapsed or Not Responded to Treatment

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00882206
First received: April 15, 2009
Last updated: January 24, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Leukemia
Lymphoma
Drug: cytarabine
Drug: decitabine
Drug: doxorubicin hydrochloride
Drug: imatinib mesylate
Drug: methotrexate
Drug: pegaspargase
Drug: prednisone
Drug: vincristine sulfate
Drug: vorinostat
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Therapeutic Trial of Decitabine (Dacogen) and Vorinostat (SAHA) in Combination With Chemotherapy (Vincristine, Prednisone, Doxorubicin and PEG-Asparaginase) for Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LL) MT2008-29R

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Response to Treatment [ Time Frame: Day 33 or Day 42 ] [ Designated as safety issue: No ]
    as measured by remission rate at day 33 (< 5% blasts) or day 42 per RECIST criteria


Secondary Outcome Measures:
  • Toxicity as measured by NCI CTCAE v3.0 [ Time Frame: From 1st Dose to 30 Days Post Treatment ] [ Designated as safety issue: Yes ]
    Measured by the National Cancer Institute's Common Toxicity Criteria for Adverse Events

  • pharmacodynamic effects of decitabine and vorinostat [ Time Frame: Baseline, Day 5 and End of Treatment ] [ Designated as safety issue: No ]
    Biological correlative endpoints will be met through the analysis of bone marrow and blood samples collected at baseline, day 5 and at the end of treatment - will include LINE methylation analysis of the leukemia cells to determine the methylation status of these relapsed/refractory leukemia/lymphomas prior to study therapy along with the impact of demethylating/HDAC inhibitor agents in these patients.


Enrollment: 14
Study Start Date: April 2009
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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)

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.

  Eligibility

Ages Eligible for Study:   2 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00882206

Locations
United States, Minnesota
University of Minnesota Amplatz Children's Hospital
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Michael J. Burke, MD Masonic Cancer Center, University of Minnesota
  More Information

Additional Information:
No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00882206     History of Changes
Other Study ID Numbers: 2008LS112, 0810M50401, MT2008-29R
Study First Received: April 15, 2009
Last Updated: January 24, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:
recurrent adult lymphoblastic lymphoma
recurrent childhood lymphoblastic lymphoma
recurrent adult acute lymphoblastic leukemia
recurrent childhood acute lymphoblastic leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Decitabine
Pegaspargase
Imatinib
Vorinostat
Asparaginase
Cytarabine
Doxorubicin
Methotrexate
Prednisone
Vincristine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents

ClinicalTrials.gov processed this record on July 24, 2014