Know Cancer

forgot password

A Phase II Study of Cloretazine® (VNP40101M) for Elderly Patients With De Novo Poor Risk Acute Myelogenous Leukemia

Phase 2
60 Years
Open (Enrolling)

Thank you

Trial Information

A Phase II Study of Cloretazine® (VNP40101M) for Elderly Patients With De Novo Poor Risk Acute Myelogenous Leukemia



- Determine the complete response rate in older patients with poor-risk, de novo acute
myeloid leukemia treated with VNP40101M as induction therapy followed by cytarabine as
consolidation therapy.


- Determine the probability of overall survival, leukemia-free survival, and
progression-free survival of patients treated with this regimen.

- Determine the safety of this regimen in these patients.

OUTLINE: This is an open-label, multicenter study.

- Induction therapy: Patients receive VNP40101M IV over 60 minutes on day 1 (course 1).
Patients without evidence of disease progression who have responding but residual
disease receive a second course of VNP40101M once between days 35-60. Patients
achieving complete response or partial response after induction therapy proceed to
consolidation therapy.

- Consolidation therapy: Beginning between days 45-90, patients receive cytarabine IV
continuously over 5 days (course 1). Patients may receive a second course of cytarabine
at the discretion of the investigator.

After completion of study treatment, patients are followed periodically for up to 36 months.

PROJECTED ACCRUAL: A total of 85 patients will be accrued for this study.

Inclusion Criteria


- Histologically confirmed de novo acute myeloid leukemia (AML)

- No acute promyelocytic leukemia [t(15;17)]

- No favorable cytogenetics, including t(15;17), t(8;21), or inv 16

- No secondary AML, defined as having a history of an antecedent hematologic
disorder (myelodysplastic syndromes [MDS] or myeloproliferative disease), or
history of prior chemotherapy or radiation for a disease other than AML

- Must have ≥ 1 of the following poor-risk features:

- Any of the following unfavorable cytogenetics:

- Del (5q)/-5q

- -7/del(7q)

- Abnormal 3q, 9q, 11q, 20q, 21q, or 17p

- t(6;9)

- t(9;22)

- Trisomy 8

- Complex karyotypes (≥ 3 unrelated abnormalities)

- At least 70 years of age

- ECOG performance status (PS) of 2

- Cardiac dysfunction* that would limit the use of anthracycline therapy, as
defined by any of the following:

- Ejection fraction ≤ 50%

- History of significant coronary artery disease, defined as ≥ 1 vessel
stenosis requiring medical treatment, stent placement, or surgical bypass

- History of congestive heart failure or myocardial infarction

- Significant arrhythmia, including any of the following:

- Atrial flutter (excluding atrial fibrillation)

- Sick sinus syndrome

- Ventricular arrhythmia

- Heart valve disease

- Mitral valve prolapse allowed

- Other heart disease, at the discretion of the principal investigator

- Pulmonary dysfunction not related to AML, defined by 1 of the following:

- DLCO and/or FEV_1 < 80% and ≥ 50% normal range

- Dyspnea on slight activity or at rest

- Requires oxygen

- Hepatic dysfunction related to chronic hepatitis or liver cirrhosis

- Other organ dysfunction or comorbidity that precludes standard cytotoxic
induction treatment (e.g., "3+7"), at the discretion of the principal
investigator NOTE: *Patients with a history of heart disease as defined above
must be on appropriate medication and have their disease under control

- No known CNS disease


- ECOG PS 0-2

- AST and ALT ≤ 5 times upper limit of normal

- Bilirubin ≤ 2.0 mg/dL

- Creatinine ≤ 2.0 mg/dL

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 6 months after
completion of study treatment

- No active, uncontrolled infection

- Patients with an infection who are under active treatment with antibiotics and
whose infections are controlled are eligible

- Chronic hepatitis allowed

- No clinical evidence of ongoing second malignancy unrelated to AML or MDS

- No evidence of left bundle branch block on screening ECG

- No obligate use of cardiac pacemaker or atrial fibrillation


- See Disease Characteristics

- At least 24 hours since prior metronidazole

- No prior low-dose, single-agent, cytotoxic chemotherapy (e.g., cytarabine,
decitabine, or azacitidine)

- No concurrent disulfiram

- No other concurrent standard or investigational therapy for AML except for the

- Concurrent hydroxyurea to control rising white blood cell counts

- Dosage must be 4-6 grams daily for up to 4 days

- Concurrent leukapheresis to control blast cell counts

- Must be completed within the first 5 days of study therapy

- No more than 2 procedures per day or 4 procedures total

- Investigational supportive care agents (e.g., antimicrobials or antifungal
agents), at the discretion of the protocol sponsor

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Complete response rate

Safety Issue:


Principal Investigator

Bonny L. Johnson, RN, MSN

Investigator Affiliation:

Vion Pharmaceuticals


United States: Food and Drug Administration

Study ID:




Start Date:

May 2006

Completion Date:

Related Keywords:

  • Leukemia
  • adult acute myeloid leukemia with 11q23 (MLL) abnormalities
  • adult acute myeloid leukemia with t(16;16)(p13;q22)
  • untreated adult acute myeloid leukemia
  • adult acute myelomonocytic leukemia (M4)
  • adult acute monocytic leukemia (M5b)
  • adult erythroleukemia (M6a)
  • adult pure erythroid leukemia (M6b)
  • adult acute monoblastic leukemia (M5a)
  • adult acute megakaryoblastic leukemia (M7)
  • adult acute basophilic leukemia
  • adult acute myeloblastic leukemia without maturation (M1)
  • adult acute myeloblastic leukemia with maturation (M2)
  • adult acute eosinophilic leukemia
  • adult acute minimally differentiated myeloid leukemia (M0)
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid



Jonsson Comprehensive Cancer Center at UCLA Los Angeles, California  90095-1781