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Cytarabine With or Without VNP40101M in Treating Patients With Relapsed Acute Myeloid Leukemia

This study has been completed.
Information provided by:
National Cancer Institute (NCI) Identifier:
First received: June 2, 2005
Last updated: November 5, 2013
Last verified: February 2009

RATIONALE: Drugs used in chemotherapy, such as cytarabine and VNP40101M, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.

PURPOSE: This randomized phase III trial is studying cytarabine and VNP40101M to see how well they work compared to cytarabine alone in treating patients with relapsed acute myeloid leukemia.

Condition Intervention Phase
Drug: cytarabine
Drug: laromustine
Other: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Phase III Randomized of Cloretazine™ (VNP40101M) and Cytosine Arabinoside (AraC) in Patients With Acute Myeloid Leukemia in First Relapse

Resource links provided by NLM:

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

Primary Outcome Measures:
  • Overall response rate

Secondary Outcome Measures:
  • Time to tumor progression
  • Duration of response
  • Overall response
  • Toxicity

Estimated Enrollment: 420
Study Start Date: March 2005
Study Completion Date: March 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Induction therapy arm I
Patients receive cytarabine IV continuously on days 1-3 and VNP40101M IV over 30-60 minutes on day 2 (at least 12 hours after the start of cytarabine).
Drug: cytarabine
Given IV
Drug: laromustine
Given IV
Active Comparator: Induction therapy arm II
Patients receive cytarabine as in arm I and placebo IV over 30-60 minutes on day 2 (at least 12 hours after the start of cytarabine).
Drug: cytarabine
Given IV
Other: placebo
Given IV

Detailed Description:



  • Compare the complete response (CR) and CR (with platelet count < 100,000/mm^3 but ≥ 20,000/mm^3 [transfusion independent for ≥ 7 consecutive days]) (CRp) rates in patients with acute myeloid leukemia in first relapse treated with cytarabine with vs without VNP40101M.


  • Compare time to progression in patients treated with these regimens.
  • Compare duration of response in patients treated with these regimens.
  • Compare the survival of patients treated with these regimens.
  • Compare the toxicity of these regimens in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, parallel group, multicenter study. Patients are stratified according to age (< 60 years vs ≥ 60 years) and duration of first complete response (CR) or CR (with platelet count < 100,000/mm³ but ≥ 20,000/mm³ [transfusion independent for ≥ 7 consecutive days]) (CRp) (< 12 months vs ≥ 12 months).

  • Induction therapy: Patients are randomized to 1 of 2 treatment arms.

    • Arm I: Patients receive cytarabine IV continuously on days 1-3 and VNP40101M IV over 30-60 minutes on day 2 (at least 12 hours after the start of cytarabine).
    • Arm II: Patients receive cytarabine as in arm I and placebo IV over 30-60 minutes on day 2 (at least 12 hours after the start of cytarabine).

In both arms, patients demonstrating at least 20% reduction of blasts in bone marrow (based on total cellularity and percent blasts) after course 1 may receive 1 additional course of induction therapy between days 35-60 in the absence of disease progression or unacceptable toxicity. Patients achieving CR or CRp after 1 or 2 courses of induction therapy proceed to consolidation therapy.

  • Consolidation therapy: Beginning 6 weeks after initial documentation of CR or CRp, patients receive 1 course of consolidation therapy, as per induction therapy, according to their randomized treatment arm. These patients may then proceed to other consolidation, maintenance, and/or intensification therapy (including stem cell transplantation) off study at the discretion of the physician.

After completion of study treatment, patients are followed monthly for 6 months, every 2 months for 6 months, and then every 3 months for 2 years.

PROJECTED ACCRUAL: A total of 420 patients (280 in arm I and 140 in arm II) will be accrued for this study within 24-30 months.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed acute myeloid leukemia (AML)

    • Any WHO classification, excluding acute promyelocytic leukemia
    • At least 10% blasts by bone marrow aspirate and/or biopsy
  • In first relapse after achieving a first complete response (CR) OR CR (with platelet count < 100,000/mm³ but ≥ 20,000/mm³ [transfusion independent for ≥ 7 consecutive days]) (CRp) that lasted ≥ 3 months but ≤ 24 months after completion of the initial induction regimen

    • Relapse confirmed by recurrence of blasts in peripheral blood, bone marrow histopathology, and/or histologically confirmed CNS or extramedullary disease



  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified


  • See Disease Characteristics


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


  • Creatinine ≤ 2.0 mg/dL


  • No myocardial infarction within the past 3 months
  • No uncontrolled arrhythmias
  • No uncontrolled congestive heart failure


  • No severe chronic obstructive pulmonary disease
  • No requirement for supplemental oxygen at rest


  • No uncontrolled active infection

    • Infections that are controlled and under active treatment with antibiotics allowed
  • No evidence of invasive fungal infection by blood or tissue cultures


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after completion of study treatment
  • No clinical evidence of another active malignancy by tumor marker, pathology, or radiologic studies
  • No other severe medical condition that would preclude study treatment


Biologic therapy

  • Not specified


  • At least 12 hours since prior hydroxyurea

Endocrine therapy

  • Not specified


  • Not specified


  • Not specified


  • No prior treatment while in first relapse except hydroxyurea
  • No other concurrent standard or investigational treatment for AML
  • No concurrent disulfiram (Antabuse®)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00112554

  Show 62 Study Locations
Sponsors and Collaborators
Vion Pharmaceuticals
OverallOfficial: Bonny L. Johnson, RN, MSN Vion Pharmaceuticals
  More Information

Publications: Identifier: NCT00112554     History of Changes
Other Study ID Numbers: CDR0000430677
Study First Received: June 2, 2005
Last Updated: November 5, 2013

Keywords provided by National Cancer Institute (NCI):
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
recurrent adult acute myeloid leukemia
adult acute basophilic leukemia
adult acute eosinophilic leukemia
adult erythroleukemia (M6a)
adult pure erythroid leukemia (M6b)
adult acute megakaryoblastic leukemia (M7)
adult acute minimally differentiated myeloid leukemia (M0)
adult acute monoblastic leukemia (M5a)
adult acute monocytic leukemia (M5b)
adult acute myeloblastic leukemia with maturation (M2)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myelomonocytic leukemia (M4)

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs processed this record on May 22, 2017