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

University of Minnesota (UMN)

Status and phase

Terminated

Phase 2

Conditions

Lymphoma

Leukemia

Treatments

Drug: imatinib mesylate

Drug: doxorubicin hydrochloride

Drug: methotrexate

Drug: pegaspargase

Drug: cytarabine

Drug: decitabine

Drug: prednisone

Drug: vincristine sulfate

Drug: vorinostat

Study type

Interventional

Funder types

Other

Identifiers

NCT00882206

0810M50401 (Other Identifier)

2008LS112

MT2008-29R (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

15 patients

Sex

All

Ages

2 to 60 years old

Volunteers

No 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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

15 participants in 1 patient group

Decitabine / Vorinostat

Experimental group

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.

Treatment: