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

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00112554
First received: June 2, 2005
Last updated: November 5, 2013
Last verified: February 2009
  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 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Double-Blind
Primary Purpose: Treatment
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:


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
Study Completion Date: March 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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).
Drug: cytarabine
Given IV
Drug: laromustine
Given IV
Active Comparator: 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).
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Hide Study Locations
Locations
United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095-1781
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90089-9181
Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
Orange, California, United States, 92868
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Connecticut
Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
Hartford, Connecticut, United States, 06105
United States, Florida
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
Veterans Affairs Medical Center - Tampa (Haley)
Tampa, Florida, United States, 33612
United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611-3013
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
United States, Indiana
American Health Network - North Meridian
Indianapolis, Indiana, United States, 46260
United States, Maryland
Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Nevada
Nevada Cancer Institute
Las Vegas, Nevada, United States, 89135
United States, New Mexico
New Mexico Cancer Care Alliance
Albuquerque, New Mexico, United States, 87106
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
New York Medical College
Valhalla, New York, United States, 10595
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
Brody School of Medicine at East Carolina University
Greenville, North Carolina, United States, 27858
United States, Ohio
Riverside Methodist Hospital Cancer Care
Columbus, Ohio, United States, 43214-3998
United States, Pennsylvania
Penn State Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, United States, 15224
United States, South Carolina
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6838
United States, Texas
M.D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Belgium
Cliniques Universitaires Saint-Luc
Brussels, Belgium, 1200
U.Z. Gasthuisberg
Leuven, Belgium, B-3000
CHU Charleroi - Site Vesale
Montigny-le-Tilleul, Belgium, 6110
Canada, British Columbia
Vancouver Hospital and Health Science Center
Vancouver, British Columbia, Canada, V5Z 4E3
Canada, New Brunswick
Saint John Regional Hospital
Saint John, New Brunswick, Canada, E2L 4L2
Canada, Newfoundland and Labrador
Memorial University of Newfoundland
St. John's, Newfoundland and Labrador, Canada, A1B 3V6
Canada, Nova Scotia
Capital District Health Authority Center for Clinical Research
Halifax, Nova Scotia, Canada, B3H 1V7
Canada, Ontario
Ottawa Hospital Regional Cancer Centre - General Campus
Ottawa, Ontario, Canada, K1H 8L6
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
France
Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz
Besancon, France, 25030
Hopital Edouard Herriot
Lyon, France, 69437
Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
Marseille, France, 13273
CHR Hotel Dieu
Nantes, France, 44093
Hopital Haut Leveque
Pessac, France, 33604
Germany
Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin
Berlin, Germany, D-12200
Medizinische Universitaetsklinik I at the University of Cologne
Cologne, Germany, D-50924
Universitaetsfrauenklinik Frankfurt
Frankfurt, Germany, D-60596
Universitatsklinikum Heidelberg
Heidelberg, Germany, D-69115
Medizinische Klinik und Poliklinik A - Universitaetsklinikum Muenster
Muenster, Germany, D-48149
Klinikum der Universitaet Muenchen - Grosshadern Campus
Munich, Germany, D-81377
University Wurzburg
Wurzburg, Germany, D-97070
Greece
Evaggelismos Hospital
Athens, Greece, 10676
University of Patras Medical School
Rio Patras, Greece, GR-26500
Netherlands
University Medical Center Groningen
Groningen, Netherlands, 9713 GZ
Poland
Medical University of Gdansk
Gdansk, Poland, 80-211
Medical University of Lodz
Lodz, Poland, 90-419
Centrum Onkologii Ziemi Lubelskiez
Lublin, Poland, 20-954
Wojskowy Instytut Medyczny
Warsaw, Poland, 00-909
Institute of Haematology and Blood Transfusion
Warsaw, Poland, 00-957
Serbia
Clinical Centre of Serbia
Belgrade, Serbia, 11000
Clinical Centre Nis
Nis, Serbia, 18000
Clinic Centre Novi Sad
Novi Sad, Serbia, 21000
United Kingdom
Birmingham Heartlands Hospital
Birmingham, England, United Kingdom, B9 5SS
Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust
Cambridge, England, United Kingdom, CB2 2QQ
Leicester Royal Infirmary
Leicester, England, United Kingdom, LE1 5WW
King's College Hospital
London, England, United Kingdom, SE5 9RS
Manchester Royal Infirmary
Manchester, England, United Kingdom, M13 9WL
University Hospital of Wales
Cardiff, Wales, United Kingdom, CF14 4XW
Sponsors and Collaborators
Vion Pharmaceuticals
Investigators
Investigator: Bonny L. Johnson, RN, MSN Vion Pharmaceuticals
  More Information

Additional Information:
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.

ClinicalTrials.gov Identifier: NCT00112554     History of Changes
Other Study ID Numbers: CDR0000430677, VION-CLI-037
Study First Received: June 2, 2005
Last Updated: November 5, 2013
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)

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms
Neoplasms by Histologic Type
Cytarabine
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014