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

NCT00112554 | Completed Phase 3

• 2 other identifiers: CDR0000430677VION-CLI-037
• Study Type: interventional
• Target: 420
• Locations: 10 countries
• Sites: 62

Brief Summary

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.

Conditions

Leukemia

Keywords

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)

Outcome Measures

Primary Outcomes (1)

• Overall response rate

Secondary Outcomes (4)

• Time to tumor progression

• Duration of response

• Overall response

• Toxicity

Study Arms (2)

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; Drug: laromustine

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; Other: placebo

Interventions

cytarabine DRUG

Given IV

Induction therapy arm I; Induction therapy arm II

laromustine DRUG

Given IV

Induction therapy arm I

placebo OTHER

Given IV

Induction therapy arm II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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®)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Vion Pharmaceuticals: lead

Study Sites (62)

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, 90089-9181, United States

Location

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, 90095-1781, United States

Location

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

Orange, California, 92868, United States

Location

UCSF Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

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

Hartford, Connecticut, 06105, United States

Location

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Veterans Affairs Medical Center - Tampa (Haley)

Tampa, Florida, 33612, United States

Location

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, 60611-3013, United States

Location

University of Chicago Cancer Research Center

Chicago, Illinois, 60637-1470, United States

Location

American Health Network - North Meridian

Indianapolis, Indiana, 46260, United States

Location

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

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

Boston, Massachusetts, 02115, United States

Location

Nevada Cancer Institute

Las Vegas, Nevada, 89135, United States

Location

New Mexico Cancer Care Alliance

Albuquerque, New Mexico, 87106, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Brody School of Medicine at East Carolina University

Greenville, North Carolina, 27858, United States

Location

Riverside Methodist Hospital Cancer Care

Columbus, Ohio, 43214-3998, United States

Location

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, 15224, United States

Location

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6838, United States

Location

M.D. Anderson Cancer Center at University of Texas

Houston, Texas, 77030-4009, United States

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

U.Z. Gasthuisberg

Leuven, B-3000, Belgium

Location

CHU Charleroi - Site Vesale

Montigny-le-Tilleul, 6110, Belgium

Location

Vancouver Hospital and Health Science Center

Vancouver, British Columbia, V5Z 4E3, Canada

Location

Saint John Regional Hospital

Saint John, New Brunswick, E2L 4L2, Canada

Location

Memorial University of Newfoundland

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

Location

Capital District Health Authority Center for Clinical Research

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Ottawa Hospital Regional Cancer Centre - General Campus

Ottawa, Ontario, K1H 8L6, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz

Besançon, 25030, France

Location

Hopital Edouard Herriot

Lyon, 69437, France

Location

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

Marseille, 13273, France

Location

CHR Hotel Dieu

Nantes, 44093, France

Location

Hopital Haut Leveque

Pessac, 33604, France

Location

Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin

Berlin, D-12200, Germany

Location

Medizinische Universitaetsklinik I at the University of Cologne

Cologne, D-50924, Germany

Location

Universitaetsfrauenklinik Frankfurt

Frankfurt, D-60596, Germany

Location

Universitatsklinikum Heidelberg

Heidelberg, D-69115, Germany

Location

Klinikum der Universitaet Muenchen - Grosshadern Campus

Munich, D-81377, Germany

Location

Medizinische Klinik und Poliklinik A - Universitaetsklinikum Muenster

Münster, D-48149, Germany

Location

University Wurzburg

Würzburg, D-97070, Germany

Location

Evaggelismos Hospital

Athens, 10676, Greece

Location

University of Patras Medical School

Rio Patras, GR-26500, Greece

Location

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

Medical University of Gdansk

Gdansk, 80-211, Poland

Location

Medical University of Lodz

Lodz, 90-419, Poland

Location

Centrum Onkologii Ziemi Lubelskiez

Lublin, 20-954, Poland

Location

Wojskowy Instytut Medyczny

Warsaw, 00-909, Poland

Location

Institute of Haematology and Blood Transfusion

Warsaw, 00-957, Poland

Location

Clinical Centre of Serbia

Belgrade, 11000, Serbia

Location

Clinical Centre Nis

Niš, 18000, Serbia

Location

Clinic Centre Novi Sad

Novi Sad, 21000, Serbia

Location

Birmingham Heartlands Hospital

Birmingham, England, B9 5SS, United Kingdom

Location

Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust

Cambridge, England, CB2 2QQ, United Kingdom

Location

Leicester Royal Infirmary

Leicester, England, LE1 5WW, United Kingdom

Location

King's College Hospital

London, England, SE5 9RS, United Kingdom

Location

Manchester Royal Infirmary

Manchester, England, M13 9WL, United Kingdom

Location

University Hospital of Wales

Cardiff, Wales, CF14 4XW, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 19710500 RESULT

• 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.

  RESULT

MeSH Terms

Conditions

Leukemia; Congenital Abnormalities; Leukemia, Myeloid, Acute; Leukemia, Basophilic, Acute; Leukemia, Eosinophilic, Acute; Leukemia, Erythroblastic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myelomonocytic, Acute

Interventions

Cytarabine; laromustine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Bonny L. Johnson, RN, MSN

  Vion Pharmaceuticals

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: June 2, 2005
• First Posted: June 3, 2005
• Study Start: March 1, 2005
• Primary Completion: March 1, 2008
• Study Completion: March 1, 2008
• Last Updated: November 6, 2013

Record last verified: 2009-02

Locations

SE (3); NL (1); GB (6); US (24); DE (7); PL (5); GR (2); CA (6); BE (3); FR (5)