Cytarabine With or Without VNP40101M in Treating Patients With Relapsed Acute Myeloid Leukemia
This study has been completed.
Sponsor:
Vion Pharmaceuticals
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00112554
First received: June 2, 2005
Last updated: December 22, 2009
Last verified: February 2009
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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 |
| 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00112554
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Hide Study LocationsLocations
| 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 | |
| Institute of Haematology and Blood Transfusion | |
| Warsaw, Poland, 00-957 | |
| Wojskowy Instytut Medyczny | |
| Warsaw, Poland, 00-909 | |
| 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: | December 22, 2009 |
| 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, Acute Leukemia, Myeloid Neoplasms by Histologic Type Neoplasms Cytarabine Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action |
Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Antiviral Agents Anti-Infective Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on June 13, 2013