Working… Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00882206
Recruitment Status : Terminated (Slow accrual)
First Posted : April 16, 2009
Results First Posted : October 28, 2016
Last Update Posted : December 28, 2017
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

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.

Condition or disease Intervention/treatment 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

Detailed Description:



  • 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.


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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Study Start Date : April 2009
Actual Primary Completion Date : January 2013
Actual Study Completion Date : January 2013

Arm Intervention/treatment
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)

Primary Outcome Measures :
  1. 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)

Secondary Outcome Measures :
  1. Level of Methylation [ Time Frame: Day 0 ]
    the percentage of methylated DNA

  2. Level of Methylation [ Time Frame: Day 5 ]
    the percentage of methylated DNA

  3. Level of Methylation [ Time Frame: Day 33 ]
    the percentage of methylated DNA

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   2 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00882206

Layout table for location information
United States, Minnesota
University of Minnesota Amplatz Children's Hospital
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Layout table for investigator information
Principal Investigator: Michael J. Burke, MD Masonic Cancer Center, University of Minnesota
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Masonic Cancer Center, University of Minnesota Identifier: NCT00882206    
Other Study ID Numbers: 2008LS112
0810M50401 ( Other Identifier: IRB, University of Minnesota )
MT2008-29R ( Other Identifier: Blood and Marrow Transplantation Program )
First Posted: April 16, 2009    Key Record Dates
Results First Posted: October 28, 2016
Last Update Posted: December 28, 2017
Last Verified: December 2017
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:
Layout table for MeSH terms
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Liposomal doxorubicin
Imatinib Mesylate
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents