VNP40101M and Cytarabine in Treating Patients With Hematologic Malignancies - Full Text View

Purpose

RATIONALE: Drugs used in chemotherapy, such as VNP40101M and cytarabine, use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

PURPOSE: Phase I trial to study the effectiveness of combining VNP40101M with cytarabine in treating patients who have hematologic malignancies, including myelodysplastic syndrome or relapsed, refractory, or untreated leukemia.

Condition	Intervention	Phase
Leukemia Myelodysplastic Syndromes	Drug: VNP40101M Drug: cytarabine	Phase I

MedlinePlus related topics:

Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for:

Cytarabine Cytarabine hydrochloride Cloretazine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label

Official Title:	A Phase I Study Of VNP40101M And Cytarabine For Patients With Hematologic Malignancies

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

Study Start Date:	June 2003
Primary Completion Date:	September 2004 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Determine the maximum tolerated dose of VP40101M when administered with cytarabine in patients with hematologic malignancies.
Determine the toxic effects of this regimen in these patients.

OUTLINE: This is an open-label, dose-escalation study of VNP40101M.

Patients receive cytarabine IV over 24 hours on days 1-4 for patients under 65 years of age OR on days 1-3 for patients 65 years of age and over. Patients also receive VNP40101M IV over 15-60 minutes on day 2. Treatment repeats every 4 weeks for up to 3 courses (in patients with responding disease) in the absence of disease progression or unacceptable toxicity. Patients with a continued response may receive additional courses at the discretion of the investigator.

Cohorts of 3-6 patients receive escalating doses of VNP40101M 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 may receive treatment 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 leukemia or myelodysplastic syndromes (MDS) meeting criteria for 1 of the following:
- Relapsed or refractory leukemia for which there is no standard therapy anticipated to result in a durable remission
  - Acute myeloid leukemia
  - Acute lymphocytic leukemia
  - Chronic myelogenous leukemia
    - In blast crisis
- Untreated leukemia and standard therapy is refused
- Any of the following poor-risk MDS:
  - Refractory anemia with excess blasts (RAEB)
  - RAEB in transformation
  - Chronic myelomonocytic leukemia
CNS leukemia allowed

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-2

Life expectancy

Not specified

Hematopoietic

Not specified

Hepatic

Bilirubin no greater than 1.5 times upper limit of normal (ULN)
ALT or AST no greater than 3 times ULN
Chronic hepatitis allowed

Renal

Creatinine no greater than 2.0 mg/dL

Cardiovascular

No active heart disease
No myocardial infarction within the past 3 months
No symptomatic coronary artery disease
No arrhythmias uncontrolled by medication
No uncontrolled congestive heart failure

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No persistent chronic toxic effects from prior chemotherapy greater than grade 1
No uncontrolled active infection
- Infections under control and under active treatment with antibiotics allowed

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

At least 48 hours since prior hydroxyurea

Endocrine therapy

Not specified

Radiotherapy

Not specified

Surgery

Not specified

Other

At least 2 weeks since prior myelosuppressive cytotoxic agents (in the absence of rapidly progressing disease)
No other concurrent standard or investigational treatment for leukemia
No concurrent disulfiram

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00070538

Locations


United States, Texas
	University of Texas - MD Anderson Cancer Center
	Houston, Texas, United States, 77030-4095

Sponsors and Collaborators

Vion Pharmaceuticals

National Cancer Institute (NCI)

Investigators


Study Chair:	Mario Sznol, MD	Vion Pharmaceuticals

More Information

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

Publications of Results:

Giles F, Verstovsek S, Thomas D, Gerson S, Cortes J, Faderl S, Ferrajoli A, Ravandi F, Kornblau S, Garcia-Manero G, Jabbour E, O'Brien S, Karsten V, Cahill A, Yee K, Albitar M, Sznol M, Kantarjian H. Phase I study of cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, combined with cytarabine in patients with refractory leukemia. Clin Cancer Res. 2005 Nov 1;11(21):7817-24.

Giles FJ, Verstovsek S, Cortes J, et al.: Phase I study of VNP40101M (101M) and AraC in patients (pts) with refractory leukemia. [Abstract] J Clin Oncol 22 (14 Suppl): A-6617, 586s, 2004.

Study ID Numbers:	CDR0000334879, VION-CLI-034, MDA-2003-0326
First Received:	October 3, 2003
Last Updated:	August 23, 2008
ClinicalTrials.gov Identifier:	NCT00070538
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent adult acute lymphoblastic leukemia

blastic phase chronic myelogenous leukemia

relapsing chronic myelogenous leukemia

chronic myelomonocytic leukemia

refractory anemia with excess blasts in transformation

refractory anemia with excess blasts

recurrent adult acute myeloid leukemia

untreated adult acute myeloid leukemia

untreated adult acute lymphoblastic leukemia

de novo myelodysplastic syndromes

previously treated myelodysplastic syndromes

secondary myelodysplastic syndromes

adult acute myeloid leukemia with t(8;21)(q22;q22)

adult acute myeloid leukemia with t(16;16)(p13;q22)

adult acute myeloid leukemia with inv(16)(p13;q22)

adult acute myeloid leukemia with 11q23 (MLL) abnormalities

adult acute myeloid leukemia with t(15;17)(q22;q12)

Study placed in the following topic categories:

Blast Crisis

Leukemia, Lymphoid

Hematologic Neoplasms

Precancerous Conditions

Chronic myelogenous leukemia

Chronic myelomonocytic leukemia

Refractory anemia

Leukemia, Myeloid, Acute

Acute lymphoblastic leukemia, adult

Leukemia

Preleukemia

Anemia, Refractory

Neoplasm Metastasis

Acute myeloid leukemia, adult

Congenital Abnormalities

Acute myelocytic leukemia

Cytarabine

Myelodysplastic syndromes

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Hematologic Diseases

Leukemia, Myelomonocytic, Chronic

Myelodysplastic Syndromes

Myelodysplasia

Acute myelogenous leukemia

Anemia

Leukemia, Myeloid

Recurrence

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Anemia, Refractory, with Excess of Blasts

Bone Marrow Diseases

Additional relevant MeSH terms:

Antimetabolites

Anti-Infective Agents

Neoplasms by Histologic Type

Disease

Antimetabolites, Antineoplastic

Immunologic Factors

Molecular Mechanisms of Pharmacological Action

Antineoplastic Agents

Physiological Effects of Drugs

Immunosuppressive Agents

Antiviral Agents

Pharmacologic Actions

Neoplasms

Pathologic Processes

Neoplasms by Site

Syndrome

Therapeutic Uses

ClinicalTrials.gov processed this record on November 30, 2008

Sponsors and Collaborators:	Vion Pharmaceuticals National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00070538