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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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