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A Phase III Randomized of Cloretazine™ (VNP40101M) and Cytosine Arabinoside (AraC) in Patients With Acute Myeloid Leukemia in First Relapse

Phase 3
18 Years
Not Enrolling

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Trial Information

A Phase III Randomized of Cloretazine™ (VNP40101M) and Cytosine Arabinoside (AraC) in Patients With Acute Myeloid Leukemia in First Relapse



- 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


- 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.

Inclusion Criteria


- 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

- 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®)

Type of Study:


Study Design:

Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Treatment

Outcome Measure:

Overall response rate

Safety Issue:


Principal Investigator

Bonny L. Johnson, RN, MSN

Investigator Affiliation:

Vion Pharmaceuticals


United States: Federal Government

Study ID:




Start Date:

March 2005

Completion Date:

Related Keywords:

  • Leukemia
  • 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)
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid



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M.D. Anderson Cancer Center at University of Texas Houston, Texas  77030
Hollings Cancer Center at Medical University of South Carolina Charleston, South Carolina  29425
Riverside Methodist Hospital Cancer Care Columbus, Ohio  43214
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Jonsson Comprehensive Cancer Center at UCLA Los Angeles, California  90095-1781
Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center Orange, California  92868
Robert H. Lurie Comprehensive Cancer Center at Northwestern University Chicago, Illinois  60611
Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center Hartford, Connecticut  06105
Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital Pittsburgh, Pennsylvania  15224-1791
Nevada Cancer Institute Las Vegas, Nevada  89135
Brody School of Medicine at East Carolina University Greenville, North Carolina  27858
American Health Network - North Meridian Indianapolis, Indiana  46260
New Mexico Cancer Care Alliance Albuquerque, New Mexico  87106