Clinical trial NCT00070538: VNP40101M and Cytarabine in Treating Patients With Hematologic Malignancies
Official title: A Phase I Study Of VNP40101M And Cytarabine For Patients With Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leukemia
Myelodysplastic Syndromes
Keywords: 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)
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-10-07
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Vion Pharmaceuticals
name: Mario Sznol, MD
role: STUDY_CHAIR
References:
citation: 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. doi: 10.1158/1078-0432.CCR-05-1070.
citation: 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.