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

Primary Purpose

Leukemia, Lymphoma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
cytarabine
decitabine
doxorubicin hydrochloride
imatinib mesylate
methotrexate
pegaspargase
prednisone
vincristine sulfate
vorinostat
Sponsored by
Masonic Cancer Center, University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring recurrent adult lymphoblastic lymphoma, recurrent childhood lymphoblastic lymphoma, recurrent adult acute lymphoblastic leukemia, recurrent childhood acute lymphoblastic leukemia

Eligibility Criteria

2 Years - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Minnesota Amplatz Children's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Decitabine / Vorinostat

Arm Description

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.

Outcomes

Primary Outcome Measures

Response to Treatment
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

Level of Methylation
the percentage of methylated DNA
Level of Methylation
the percentage of methylated DNA
Level of Methylation
the percentage of methylated DNA

Full Information

First Posted
April 15, 2009
Last Updated
December 3, 2017
Sponsor
Masonic Cancer Center, University of Minnesota
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1. Study Identification

Unique Protocol Identification Number
NCT00882206
Brief Title
Pre-reinductive Decitabine and Vorinostat in Relapsed Lymphoblastic Lymphoma or Acute Lymphoblastic Leukemia
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 Type
Interventional

2. Study Status

Record Verification Date
December 2017
Overall Recruitment Status
Terminated
Why Stopped
Slow accrual
Study Start Date
April 2009 (undefined)
Primary Completion Date
January 2013 (Actual)
Study Completion Date
January 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Masonic Cancer Center, University of Minnesota

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphoma
Keywords
recurrent adult lymphoblastic lymphoma, recurrent childhood lymphoblastic lymphoma, recurrent adult acute lymphoblastic leukemia, recurrent childhood acute lymphoblastic leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Decitabine / Vorinostat
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
cytarabine
Other Intervention Name(s)
cytosine arabinoside
Intervention Description
At baseline when peripheral blood draw and bone marrow aspirate performed. *Intrathecal Cytarabine administered dependent upon age - ranging from 30 mg to 70 mg.
Intervention Type
Drug
Intervention Name(s)
decitabine
Other Intervention Name(s)
Dacogen(R)
Intervention Description
Days 1-4, 15 mg/m^2 intravenously (IV) over 1 hour
Intervention Type
Drug
Intervention Name(s)
doxorubicin hydrochloride
Other Intervention Name(s)
Doxorubicin
Intervention Description
Day 5, 60 mg/m^2 intravenously (IV) over 15 minutes
Intervention Type
Drug
Intervention Name(s)
imatinib mesylate
Other Intervention Name(s)
Gleevec(R)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
methotrexate
Other Intervention Name(s)
MTX
Intervention Description
**Intrathecal Methotrexate administered dependent upon age - ranging from 8 mg to 15 mg.
Intervention Type
Drug
Intervention Name(s)
pegaspargase
Other Intervention Name(s)
PEG asparaginase
Intervention Description
2,500 IU/m2 IM or IV q week (days 6, 12, 19, 26)
Intervention Type
Drug
Intervention Name(s)
prednisone
Intervention Description
40mg/m2/day divided BID (days 5 - 33)
Intervention Type
Drug
Intervention Name(s)
vincristine sulfate
Other Intervention Name(s)
Oncovin(R)
Intervention Description
1.5mg/m2 (max 2 mg) iv push q week (days 5, 12, 19, 26)
Intervention Type
Drug
Intervention Name(s)
vorinostat
Other Intervention Name(s)
suberoylanilide hydroxamic acid (SAHA)
Intervention Description
Days 1-4, (230 mg/m2)orally divided twice a day (max dose 400 mg daily)
Primary Outcome Measure Information:
Title
Response to Treatment
Description
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)
Time Frame
Day 33
Secondary Outcome Measure Information:
Title
Level of Methylation
Description
the percentage of methylated DNA
Time Frame
Day 0
Title
Level of Methylation
Description
the percentage of methylated DNA
Time Frame
Day 5
Title
Level of Methylation
Description
the percentage of methylated DNA
Time Frame
Day 33

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael J. Burke, MD
Organizational Affiliation
Masonic Cancer Center, University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Minnesota Amplatz Children's Hospital
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24891274
Citation
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.
Results Reference
derived

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

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