Decitabine, Vorinostat, and Combination Chemotherapy in Treating Patients With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma That Has Relapsed or Not Responded to Treatment - Full Text View

Sponsors and Collaborators:	Masonic Cancer Center, University of Minnesota National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00882206

Purpose

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. Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving more than one drug (combination chemotherapy) together with vorinostat may kill more cancer cells.

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	Intervention	Phase
Leukemia Lymphoma	Drug: cytarabine Drug: decitabine Drug: doxorubicin hydrochloride Drug: imatinib mesylate Drug: methotrexate Drug: pegaspargase Drug: prednisone Drug: vincristine sulfate Drug: vorinostat Genetic: DNA methylation analysis Genetic: gene expression analysis Other: laboratory biomarker analysis	Phase II

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Lymphoma

Drug Information available for: Prednisone Vincristine Methotrexate Cytarabine hydrochloride Doxorubicin Doxorubicin hydrochloride Myocet Pegaspargase Suberoylanilide hydroxamic acid Imatinib Imatinib mesylate Cytarabine Vincristine sulfate 5-Aza-2'-deoxycytidine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Therapeutic Trial of Decitabine (Dacogen) and Vorinostat (SAHA) in Combination With Chemotherapy (Vincristine, Prednisone, Doxorubicin and PEG-Asparaginase) for Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LL) MT2008-29R

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Efficacy as measured by remission rate at day 33 (< 5% blasts) or day 42 per RECIST criteria [ Designated as safety issue: No ]

Secondary Outcome Measures:

Toxicity as measured by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
Biological correlative endpoints at baseline, on day 5, and at the end of study treatment [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	April 2009
Estimated Primary Completion Date:	November 2011 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

To determine the efficacy of decitabine and vorinostat when administered before intensive induction chemotherapy, in terms of end-of-induction remission rates, in patients with relapsed or refractory acute lymphoblastic leukemia or lymphoblastic lymphoma.

Secondary

To characterize the toxicities of decitabine and vorinostat when administered before intensive induction chemotherapy in these patients.
To explore the pharmacodynamic effects of decitabine and vorinostat in these patients.

OUTLINE: Patients are stratified according to age (≥ 18 years vs < 18 years).

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 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, and at the end of study treatment for correlative laboratory studies.

Samples are analyzed for methylated genes (e.g., p15, ER, DAPK, and MRD1).

After completion of study treatment, patients are followed for 60 days.

Eligibility

Ages Eligible for Study:	2 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

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)
CNS-positive disease allowed

PATIENT CHARACTERISTICS:

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
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

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
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
- No evidence of graft-versus-host disease
No concurrent valproic acid
No concurrent coumadin/warfarin other than a short course administered in a prophylactic setting

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00882206

Locations

United States, Minnesota
University of Minnesota Children's Hospital - Fairview	Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Clinical Trials Office - University of Minnesota Children's Ho 612-273-3000

Sponsors and Collaborators

Masonic Cancer Center, University of Minnesota

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Michael J. Burke, MD

Masonic Cancer Center, University of Minnesota

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Masonic Cancer Center at University of Minnesota ( Michael J. Burke )
Study ID Numbers:	CDR0000639307, UMN-2008LS112, 0810M50401, MT2008-29R
Study First Received:	April 15, 2009
Last Updated:	April 30, 2009
ClinicalTrials.gov Identifier:	NCT00882206 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Anticarcinogenic Agents
Anti-Inflammatory Agents
Acute Lymphoblastic Leukemia, Childhood
Antimetabolites
Prednisone
Leukemia, Lymphoid
Immunologic Factors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Protein Kinase Inhibitors
Hormones
Lymphoblastic Lymphoma
Anti-Bacterial Agents
Leukemia
Pegaspargase

Methotrexate
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Lymphoma
Cytarabine
Acute Lymphoblastic Leukemia
Asparaginase
Immunoproliferative Disorders
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Antineoplastic Agents, Hormonal
Vorinostat
Vincristine
Antimitotic Agents
Decitabine
Folic Acid Antagonists

Additional relevant MeSH terms:

Anticarcinogenic Agents
Anti-Inflammatory Agents
Prednisone
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Protein Kinase Inhibitors
Hormones
Pegaspargase
Therapeutic Uses
Abortifacient Agents
Methotrexate
Dermatologic Agents

Nucleic Acid Synthesis Inhibitors
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Immune System Diseases
Antineoplastic Agents, Hormonal
Vincristine
Abortifacient Agents, Nonsteroidal
Glucocorticoids
Doxorubicin
Imatinib
Neoplasms
Lymphoma, Non-Hodgkin
Antineoplastic Agents, Phytogenic
Antimetabolites
Leukemia, Lymphoid

ClinicalTrials.gov processed this record on May 06, 2009