Temozolomide and VNP40101M in Treating Patients With Relapsed or Refractory Leukemias - Full Text View

Sponsor:	Vion Pharmaceuticals
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00098436

Purpose

RATIONALE: Drugs used in chemotherapy, such as temozolomide and VNP40101M, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Temozolomide may also help VNP40101M kill more cancer cells by making cancer cells more sensitive to the drug. Giving temozolomide together with VNP40101M may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of temozolomide and VNP40101M in treating patients with relapsed or refractory leukemias.

Condition	Intervention	Phase
Leukemia	Drug: laromustine Drug: temozolomide	Phase I

Study Type:	Interventional
Study Design:	Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I Study Of Cloretazine™ (VNP40101M) And Temozolomide In Patients With Hematologic Malignancies

Resource links provided by NLM:

MedlinePlus related topics: Acute Myeloid Leukemia Cancer Leukemia

Drug Information available for: Temozolomide Cloretazine

U.S. FDA Resources

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

Estimated Enrollment:	25
Study Start Date:	September 2004
Primary Completion Date:	October 2006 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Determine the maximum tolerated dose of temozolomide and VNP40101M in patients with relapsed or refractory leukemias.
Determine the toxic effects of this regimen in these patients.

OUTLINE: This is an open-label, dose-escalation, multicenter study.

Patients receive oral temozolomide twice daily on days 1-3 (for 5 doses) followed by VNP401010M IV over 15-60 minutes on day 3 (course 1). Patients achieving a complete or partial response or having ≥ 50% reduction in bone marrow blasts may receive a second course of therapy no earlier than day 43. Courses may be repeated approximately every 6 weeks at the discretion of the sponsor and in the absence of disease progression or unacceptable toxicity.

Cohorts of 6 patients receive escalating doses of temozolomide until a dose that depletes leukemic blast AGT in at least 4 of 6 patients is determined. Once this dose is determined, cohorts of 3-6 patients receive escalating doses of VNP401010M until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 10 patients are treated at the MTD.

PROJECTED ACCRUAL: Approximately 25 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of 1 of the following:
- Acute myeloid leukemia
- Acute lymphoblastic leukemia
- Chronic myelogenous leukemia in blast crisis
Relapsed or refractory disease
No known standard therapy that is anticipated to result in a durable remission exists
CNS leukemia allowed

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-2

Life expectancy

Not specified

Hematopoietic

Not specified

Hepatic

Bilirubin ≤ 1.5 times upper limit of normal (ULN)
ALT or AST ≤ 3 times ULN
Chronic hepatitis allowed

Renal

Creatinine ≤ 2.0 mg/dL

Cardiovascular

No active heart disease, including any of the following:
- Myocardial infarction within the past 3 months
- Symptomatic coronary artery disease
- Arrhythmias not controlled by medication
- Uncontrolled congestive heart failure

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after study participation
No uncontrolled active infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

Concurrent hydroxyurea allowed within the first 10 days of study drug administration for control of elevated blast levels or platelet counts
- Maximum hydroxyurea dose 5 g daily
No persistent chronic toxic effects from prior chemotherapy > grade 1

Endocrine therapy

Not specified

Radiotherapy

Not specified

Surgery

Not specified

Other

Recovered from all prior therapy
At least 2 weeks since prior myelosuppressive cytotoxic agents (in the absence of rapidly progressive disease)
No more than 2 leukapheresis procedures within the first 10 days of study drug administration for control of elevated blast levels or platelet counts
No concurrent disulfiram
No other concurrent anticancer drugs
No other concurrent standard or investigational treatment for leukemia

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00098436

Locations

United States, Indiana
American Health Network - North Illinois Street
Indianapolis, Indiana, United States, 46202
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Ohio
Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195

Sponsors and Collaborators

Vion Pharmaceuticals

Investigators

Study Chair:

Bonny L. Johnson, RN, MSN

Vion Pharmaceuticals

More Information

Additional Information:

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

Publications:

Rizzieri D, LoRusso S, Tse W, Khan K, Advani A, Moore J, Karsten V, Cahill A, Gerson SL. Phase I study of temozolomide and laromustine (VNP40101M) in patients with relapsed or refractory leukemia. Clin Lymphoma Myeloma Leuk. 2010 Jun;10(3):211-6.

ClinicalTrials.gov Identifier:	NCT00098436 History of Changes
Other Study ID Numbers:	CDR0000405825, VION-CLI-036, CWRU-050419
Study First Received:	December 7, 2004
Last Updated:	August 27, 2010
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
blastic phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
secondary acute myeloid leukemia

adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)

Additional relevant MeSH terms:

Leukemia
Neoplasms by Histologic Type
Neoplasms
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating

Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 09, 2012