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

NCT00882206 | Terminated Phase 2 Results DMC

• 3 other identifiers: 2008LS1120810M50401MT2008-29R
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Leukemia; Lymphoma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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)

  Day 33

Secondary Outcomes (3)

• Level of Methylation

  Day 0

• Level of Methylation

  Day 5

• Level of Methylation

  Day 33

Study Arms (1)

Decitabine / Vorinostat

EXPERIMENTAL

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; Drug: decitabine; Drug: doxorubicin hydrochloride; Drug: imatinib mesylate; Drug: methotrexate; Drug: pegaspargase; Drug: prednisone; Drug: vincristine sulfate; Drug: vorinostat

Interventions

cytarabine 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.

Also known as: cytosine arabinoside

Decitabine / Vorinostat

decitabine DRUG

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

Also known as: Dacogen(R)

Decitabine / Vorinostat

doxorubicin hydrochloride DRUG

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

Also known as: Doxorubicin

Decitabine / Vorinostat

imatinib mesylate 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.

Also known as: Gleevec(R)

Decitabine / Vorinostat

methotrexate DRUG

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

Also known as: MTX

Decitabine / Vorinostat

pegaspargase DRUG

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

Also known as: PEG asparaginase

Decitabine / Vorinostat

prednisone DRUG

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

Decitabine / Vorinostat

vincristine sulfate DRUG

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

Also known as: Oncovin(R)

Decitabine / Vorinostat

vorinostat DRUG

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

Also known as: suberoylanilide hydroxamic acid (SAHA)

Decitabine / Vorinostat

Eligibility Criteria

• Age: 2 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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:
• mg/dL (for patients 1 to 5 months of age)
• mg/dL (for patients 6 to 11 months of age)
• mg/dL (for patients 1 year of age)
• mg/dL (for patients 2 to 5 years of age)
• mg/dL (for patients 6 to 9 years of age)
• mg/dL (for patients 10 to 12 years of age)
• mg/dL (males) or 1.4 mg/dL (females) (for patients 13 to 15 years of age)
• mg/dL (males) or 1.4 mg/dL (females) (for patients ≥ 16 years of age)

You may not qualify if:

• 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

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

University of Minnesota Amplatz Children's Hospital

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (1)

• 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.

  PMID: 24891274 DERIVED

MeSH Terms

Conditions

Leukemia; Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Cytarabine; Decitabine; Doxorubicin; Imatinib Mesylate; Methotrexate; pegaspargase; Prednisone; Vincristine; Vorinostat

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Azacitidine; Aza Compounds; Organic Chemicals; Ribonucleosides; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Benzamides; Amides; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Piperazines; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Anilides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids

Results Point of Contact

• Title: Dr. Michael Burke, MD
• Organization: University of Minnesota, Pediatric Hematology Dept.

612.672.7422

Study Officials

• Michael J. Burke, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2009
• First Posted: April 16, 2009
• Study Start: April 1, 2009
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: December 28, 2017
• Results First Posted: October 28, 2016

Record last verified: 2017-12

Locations

US (1)