Cytarabine With or Without VNP40101M in Treating Patients With Relapsed Acute Myeloid Leukemia - Full Text View

Sponsored by:	Vion Pharmaceuticals
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00112554

Purpose

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
Leukemia	Drug: cytarabine Drug: laromustine Other: placebo	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control
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:

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Cytarabine hydrochloride Cloretazine Cytarabine

U.S. FDA Resources

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

Primary Outcome Measures:

Overall response rate [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time to tumor progression [ Designated as safety issue: No ]
Duration of response [ Designated as safety issue: No ]
Overall response [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]

Estimated Enrollment:	420
Study Start Date:	March 2005
Primary Completion Date:	March 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Induction therapy arm I: Experimental 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
Induction therapy arm II: Active Comparator 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:

OBJECTIVES:

Primary

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.

Secondary

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-2

Life expectancy

Not specified

Hematopoietic

See Disease Characteristics

Hepatic

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

Renal

Creatinine ≤ 2.0 mg/dL

Cardiovascular

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

Pulmonary

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

Immunologic

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

Other

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

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

At least 12 hours since prior hydroxyurea

Endocrine therapy

Not specified

Radiotherapy

Not specified

Surgery

Not specified

Other

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00112554

Show 62 Study Locations

Sponsors and Collaborators

Vion Pharmaceuticals

Investigators

Investigator:

Bonny L. Johnson, RN, MSN

Vion Pharmaceuticals

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Giles FJ, Stock W, Vey N, et al.: A double blind placebo-controlled randomized phase III study of high dose continuous infusion cytosine arabinoside (araC) with or without cloretazine in patients with first relapse of acute myeloid leukemia (AML). [Abstract] Blood 108 (11): A-1970, 2006.

Study ID Numbers:	CDR0000430677, VION-CLI-037
Study First Received:	June 2, 2005
Last Updated:	February 18, 2009
ClinicalTrials.gov Identifier:	NCT00112554 History of Changes
Health Authority:	United States: Federal Government

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)

Study placed in the following topic categories:

Antimetabolites
Leukemia, Monocytic, Acute
Anti-Infective Agents
Immunologic Factors
Acute Myelomonocytic Leukemia
Leukemia, Myeloid
Acute Monoblastic Leukemia
Leukemia, Myeloid, Acute
Immunosuppressive Agents
Antiviral Agents

Recurrence
Leukemia, Myelomonocytic, Acute
Leukemia
Acute Myelocytic Leukemia
Acute Erythroblastic Leukemia
Leukemia, Erythroblastic, Acute
Acute Myeloid Leukemia, Adult
Congenital Abnormalities
Cytarabine
Di Guglielmo's Syndrome

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Leukemia, Myeloid

Leukemia, Myeloid, Acute
Immunosuppressive Agents
Antiviral Agents
Pharmacologic Actions
Leukemia
Neoplasms
Therapeutic Uses
Cytarabine

ClinicalTrials.gov processed this record on August 30, 2009