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

NCT ID: NCT00882206

Last Updated: 2017-12-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-30
• Study Completion Date: 2013-01-31

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.

Conditions

Leukemia; Lymphoma

Keywords

recurrent adult lymphoblastic lymphoma; recurrent childhood lymphoblastic lymphoma; recurrent adult acute lymphoblastic leukemia; recurrent childhood acute lymphoblastic leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

cytarabine

Intervention Type: DRUG

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

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

decitabine

Intervention Type: DRUG

Days 1-4, 15 mg/m\^2 intravenously (IV) over 1 hour

doxorubicin hydrochloride

Intervention Type: DRUG

Day 5, 60 mg/m\^2 intravenously (IV) over 15 minutes

imatinib mesylate

Intervention Type: DRUG

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.

methotrexate

Intervention Type: DRUG

\*\*Intrathecal Methotrexate administered dependent upon age - ranging from 8 mg to 15 mg.

pegaspargase

Intervention Type: DRUG

2,500 IU/m2 IM or IV q week (days 6, 12, 19, 26)

prednisone

Intervention Type: DRUG

40mg/m2/day divided BID (days 5 - 33)

vincristine sulfate

Intervention Type: DRUG

1.5mg/m2 (max 2 mg) iv push q week (days 5, 12, 19, 26)

vorinostat

Intervention Type: DRUG

Days 1-4, (230 mg/m2)orally divided twice a day (max dose 400 mg daily)

Interventions

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.

Intervention Type: DRUG

decitabine

Days 1-4, 15 mg/m\^2 intravenously (IV) over 1 hour

Intervention Type: DRUG

doxorubicin hydrochloride

Day 5, 60 mg/m\^2 intravenously (IV) over 15 minutes

Intervention Type: 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.

Intervention Type: DRUG

methotrexate

\*\*Intrathecal Methotrexate administered dependent upon age - ranging from 8 mg to 15 mg.

Intervention Type: DRUG

pegaspargase

2,500 IU/m2 IM or IV q week (days 6, 12, 19, 26)

Intervention Type: DRUG

prednisone

40mg/m2/day divided BID (days 5 - 33)

Intervention Type: DRUG

vincristine sulfate

1.5mg/m2 (max 2 mg) iv push q week (days 5, 12, 19, 26)

Intervention Type: DRUG

vorinostat

Days 1-4, (230 mg/m2)orally divided twice a day (max dose 400 mg daily)

Intervention Type: DRUG

Other Intervention Names

cytosine arabinoside; Dacogen(R); Doxorubicin; Gleevec(R); MTX; PEG asparaginase; Oncovin(R); suberoylanilide hydroxamic acid (SAHA)

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

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

• Evidence of graft-versus-host disease
• Concurrent valproic acid
• Concurrent coumadin/warfarin other than a short course administered in a prophylactic setting

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael J. Burke, MD

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

University of Minnesota Amplatz Children's Hospital

Minneapolis, Minnesota, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 24891274 (View on PubMed)

Other Identifiers

0810M50401

Identifier Type: OTHER

Identifier Source: secondary_id

MT2008-29R

Identifier Type: OTHER

Identifier Source: secondary_id

2008LS112

Identifier Type: -

Identifier Source: org_study_id