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

NCT ID: NCT00112554

Last Updated: 2013-11-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

420 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-03-31

Study Completion Date

2008-03-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Leukemia

Keywords

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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 Design

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Allocation Method

RANDOMIZED

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Study Groups

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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).

Group Type EXPERIMENTAL

cytarabine

Intervention Type DRUG

Given IV

laromustine

Intervention Type DRUG

Given IV

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).

Group Type ACTIVE_COMPARATOR

cytarabine

Intervention Type DRUG

Given IV

placebo

Intervention Type OTHER

Given IV

Interventions

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cytarabine

Given IV

Intervention Type DRUG

laromustine

Given IV

Intervention Type DRUG

placebo

Given IV

Intervention Type OTHER

Eligibility Criteria

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Inclusion 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®)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Vion Pharmaceuticals

INDUSTRY

Sponsor Role lead

Principal Investigators

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Bonny L. Johnson, RN, MSN

Role:

Vion Pharmaceuticals

Locations

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USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, United States

Site Status

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, United States

Site Status

Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center

Orange, California, United States

Site Status

UCSF Comprehensive Cancer Center

San Francisco, California, United States

Site Status

Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center

Hartford, Connecticut, United States

Site Status

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Site Status

Veterans Affairs Medical Center - Tampa (Haley)

Tampa, Florida, United States

Site Status

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, United States

Site Status

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Site Status

American Health Network - North Meridian

Indianapolis, Indiana, United States

Site Status

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Nevada Cancer Institute

Las Vegas, Nevada, United States

Site Status

New Mexico Cancer Care Alliance

Albuquerque, New Mexico, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

New York Medical College

Valhalla, New York, United States

Site Status

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Site Status

Brody School of Medicine at East Carolina University

Greenville, North Carolina, United States

Site Status

Riverside Methodist Hospital Cancer Care

Columbus, Ohio, United States

Site Status

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, United States

Site Status

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

M.D. Anderson Cancer Center at University of Texas

Houston, Texas, United States

Site Status

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Site Status

U.Z. Gasthuisberg

Leuven, , Belgium

Site Status

CHU Charleroi - Site Vesale

Montigny-le-Tilleul, , Belgium

Site Status

Vancouver Hospital and Health Science Center

Vancouver, British Columbia, Canada

Site Status

Saint John Regional Hospital

Saint John, New Brunswick, Canada

Site Status

Memorial University of Newfoundland

St. John's, Newfoundland and Labrador, Canada

Site Status

Capital District Health Authority Center for Clinical Research

Halifax, Nova Scotia, Canada

Site Status

Ottawa Hospital Regional Cancer Centre - General Campus

Ottawa, Ontario, Canada

Site Status

Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status

Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz

Besançon, , France

Site Status

Hopital Edouard Herriot

Lyon, , France

Site Status

Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes

Marseille, , France

Site Status

CHR Hotel Dieu

Nantes, , France

Site Status

Hopital Haut Leveque

Pessac, , France

Site Status

Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin

Berlin, , Germany

Site Status

Medizinische Universitaetsklinik I at the University of Cologne

Cologne, , Germany

Site Status

Universitaetsfrauenklinik Frankfurt

Frankfurt, , Germany

Site Status

Universitatsklinikum Heidelberg

Heidelberg, , Germany

Site Status

Klinikum der Universitaet Muenchen - Grosshadern Campus

Munich, , Germany

Site Status

Medizinische Klinik und Poliklinik A - Universitaetsklinikum Muenster

Münster, , Germany

Site Status

University Wurzburg

Würzburg, , Germany

Site Status

Evaggelismos Hospital

Athens, , Greece

Site Status

University of Patras Medical School

Rio Patras, , Greece

Site Status

University Medical Center Groningen

Groningen, , Netherlands

Site Status

Medical University of Gdansk

Gdansk, , Poland

Site Status

Medical University of Lodz

Lodz, , Poland

Site Status

Centrum Onkologii Ziemi Lubelskiez

Lublin, , Poland

Site Status

Wojskowy Instytut Medyczny

Warsaw, , Poland

Site Status

Institute of Haematology and Blood Transfusion

Warsaw, , Poland

Site Status

Clinical Centre of Serbia

Belgrade, , Serbia

Site Status

Clinical Centre Nis

Niš, , Serbia

Site Status

Clinic Centre Novi Sad

Novi Sad, , Serbia

Site Status

Birmingham Heartlands Hospital

Birmingham, England, United Kingdom

Site Status

Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust

Cambridge, England, United Kingdom

Site Status

Leicester Royal Infirmary

Leicester, England, United Kingdom

Site Status

King's College Hospital

London, England, United Kingdom

Site Status

Manchester Royal Infirmary

Manchester, England, United Kingdom

Site Status

University Hospital of Wales

Cardiff, Wales, United Kingdom

Site Status

Countries

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Serbia and Montenegro United States Belgium Canada France Germany Greece Netherlands Poland Serbia United Kingdom

References

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Giles F, Vey N, DeAngelo D, Seiter K, Stock W, Stuart R, Boskovic D, Pigneux A, Tallman M, Brandwein J, Kell J, Robak T, Staib P, Thomas X, Cahill A, Albitar M, O'Brien S. Phase 3 randomized, placebo-controlled, double-blind study of high-dose continuous infusion cytarabine alone or with laromustine (VNP40101M) in patients with acute myeloid leukemia in first relapse. Blood. 2009 Nov 5;114(19):4027-33. doi: 10.1182/blood-2009-06-229351. Epub 2009 Aug 26.

Reference Type RESULT
PMID: 19710500 (View on PubMed)

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.

Reference Type RESULT

Other Identifiers

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VION-CLI-037

Identifier Type: -

Identifier Source: secondary_id

CDR0000430677

Identifier Type: -

Identifier Source: org_study_id