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

Leukemia Clinical Trial

Official title:

A Phase III Randomized of Cloretazine™ (VNP40101M) and Cytosine Arabinoside (AraC) in Patients With Acute Myeloid Leukemia in First Relapse

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00112554
• Other study ID #: CDR0000430677
• Secondary ID: VION-CLI-037
• Status: Completed
• Phase: Phase 3
• First received: June 2, 2005
• Last updated: November 5, 2013
• Start date: March 2005
• Est. completion date: March 2008

Study information

• Verified date: February 2009
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 420
• Est. completion date: March 2008
• Est. primary completion date: March 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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®)

Study Design

Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• cytarabine
Given IV
• laromustine
Given IV

Other:
• placebo
Given IV

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	U.Z. Gasthuisberg	Leuven
Belgium	CHU Charleroi - Site Vesale	Montigny-le-Tilleul
Canada	Capital District Health Authority Center for Clinical Research	Halifax	Nova Scotia
Canada	Ottawa Hospital Regional Cancer Centre - General Campus	Ottawa	Ontario
Canada	Saint John Regional Hospital	Saint John	New Brunswick
Canada	Memorial University of Newfoundland	St. John's	Newfoundland and Labrador
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	Vancouver Hospital and Health Science Center	Vancouver	British Columbia
France	Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz	Besancon
France	Hopital Edouard Herriot	Lyon
France	Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes	Marseille
France	CHR Hotel Dieu	Nantes
France	Hopital Haut Leveque	Pessac
Germany	Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin	Berlin
Germany	Medizinische Universitaetsklinik I at the University of Cologne	Cologne
Germany	Universitaetsfrauenklinik Frankfurt	Frankfurt
Germany	Universitatsklinikum Heidelberg	Heidelberg
Germany	Medizinische Klinik und Poliklinik A - Universitaetsklinikum Muenster	Muenster
Germany	Klinikum der Universitaet Muenchen - Grosshadern Campus	Munich
Germany	University Wurzburg	Wurzburg
Greece	Evaggelismos Hospital	Athens
Greece	University of Patras Medical School	Rio Patras
Netherlands	University Medical Center Groningen	Groningen
Poland	Medical University of Gdansk	Gdansk
Poland	Medical University of Lodz	Lodz
Poland	Centrum Onkologii Ziemi Lubelskiez	Lublin
Poland	Institute of Haematology and Blood Transfusion	Warsaw
Poland	Wojskowy Instytut Medyczny	Warsaw
Serbia	Clinical Centre of Serbia	Belgrade
Serbia	Clinical Centre Nis	Nis
Serbia	Clinic Centre Novi Sad	Novi Sad
United Kingdom	Birmingham Heartlands Hospital	Birmingham	England
United Kingdom	Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust	Cambridge	England
United Kingdom	University Hospital of Wales	Cardiff	Wales
United Kingdom	Leicester Royal Infirmary	Leicester	England
United Kingdom	King's College Hospital	London	England
United Kingdom	Manchester Royal Infirmary	Manchester	England
United States	New Mexico Cancer Care Alliance	Albuquerque	New Mexico
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Riverside Methodist Hospital Cancer Care	Columbus	Ohio
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Brody School of Medicine at East Carolina University	Greenville	North Carolina
United States	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut
United States	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	M.D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	American Health Network - North Meridian	Indianapolis	Indiana
United States	Nevada Cancer Institute	Las Vegas	Nevada
United States	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	University of Miami Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center	Orange	California
United States	Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital	Pittsburgh	Pennsylvania
United States	UCSF Comprehensive Cancer Center	San Francisco	California
United States	Veterans Affairs Medical Center - Tampa (Haley)	Tampa	Florida
United States	New York Medical College	Valhalla	New York

Sponsors (1)

Lead Sponsor	Collaborator
Vion Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Greece,  Netherlands,  Poland,  Serbia,  United Kingdom, 

References & 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 — View Citation

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). [Abstra

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate			No
Secondary	Time to tumor progression			No
Secondary	Duration of response			No
Secondary	Overall response			No
Secondary	Toxicity			Yes