A Study of Clofarabine and Cytarabine for Older Patients With Relapsed or Refractory Acute Myelogenous Leukemia (AML)(CLASSIC I)

NCT00317642 | Completed Phase 3 Results DMC

• 2 other identifiers: CLO341004052008-001043-19
• Study Type: interventional
• Target: 326
• Locations: 5 countries
• Sites: 57

Brief Summary

Clofarabine (injection) is approved by the Food and Drug Administration (FDA) for the treatment of pediatric patients 1 to 21 years old with relapsed acute or refractory lymphoblastic leukemia (ALL) who have had at least 2 prior treatment regimens. There is no recommended standard treatment for relapsed or refractory acute myelogenous leukemia in older patients. Cytarabine is the most commonly used drug to treat these patients. This study will determine if there is benefit by combining clofarabine with cytarabine. Patients will be randomized to receive up to 3 cycles of treatment with either placebo in combination with cytarabine or clofarabine in combination with cytarabine. Randomization was stratified by remission status following the first induction regimen (no remission \[i.e., CR1 = refractory\] or remission \<6 months vs CR1 = remission ≥6 months). CR1 is defined as remission after first pre-study induction regimen. The safety and tolerability of clofarabine in combination with cytarabine and cytarabine alone will be monitored throughout the study.

Conditions

Acute Myelogenous Leukemia

Keywords

acute myelogenous leukemia; acute myeloid leukemia; relapsed AML; refractory AML; clofarabine; cytarabine; CLO341; clolar

Outcome Measures

Primary Outcomes (2)

• Overall Survival - Overall and by Calculated Strata (CSR 7-April-11)

  Overall survival (OS) for the Full Analysis Set (FAS) and for the 2 calculated strata. OS was defined as the number of months from date of randomization until date of death due to any cause.

  Day 1 (randomization) up to approximately 4 years

• Overall Survival - Overall and by Randomized Strata (CSR 9-July-12)

  Overall survival (OS) for the Full Analysis Set (FAS) and for the 2 randomized strata. OS was defined as the number of months from date of randomization until date of death due to any cause.

  Day 1 (randomization) up to approximately 4 years

Secondary Outcomes (10)

• Best Response Per Independent Response Review Panel (IRRP) Assessment - Overall and by Calculated Strata (CSR 7-April-11)

  Day 12 up to approximately 6 months

• Duration of Remission (DOR) Per IRRP Assessment-Overall and by Calculated Strata (CSR 7-April-11)

  Day 12 to approximately 4 years

• Duration of Remission (DOR) Per IRRP Assessment-Overall and by Randomized Strata (CSR 9-July-12)

  Day 12 to approximately 4 years

• Disease-free Survival by IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11)

  Day 12 to approximately 4 years

• Disease-free Survival by IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12)

  Day 12 to approximately 4 years

Study Arms (2)

clofarabine (IV formulation) and cytarabine

EXPERIMENTAL

Participants received clofarabine (40 mg/m\^2) administered as a 1-hour infusion followed 3 hours later (from end of infusion) by cytarabine 1 g/m\^2 administered as a 2-hour infusion. Participants could receive up to 3 cycles of treatment (induction, re-induction, and consolidation) Complete induction cycle = 5 consecutive days of treatment Re-induction cycle = 5 consecutive days of treatment at the original or modified dose Consolidation cycle = 4 consecutive days of treatment at the original or modified dose

Drug: clofarabine (IV formulation); Drug: cytarabine

placebo and cytarabine

EXPERIMENTAL

Participants received placebo administered as a 1-hour infusion followed 3 hours later (from end of infusion) by cytarabine 1 g/m\^2 administered as a 2-hour infusion. Patients could receive up to 3 cycles of treatment (induction, re-induction, and consolidation)

Drug: placebo; Drug: cytarabine

Interventions

clofarabine (IV formulation) DRUG

clofarabine (IV formulation) infusion 40mg/m\^2 / day up to 3 cycles

Also known as: Clolar®, Evoltra®

clofarabine (IV formulation) and cytarabine

placebo DRUG

placebo (sodium Chloride) 1-hour IV infusion

placebo and cytarabine

cytarabine DRUG

cytarabine IV infusion 1g/m\^2/day for up to 3 cycles

clofarabine (IV formulation) and cytarabine; placebo and cytarabine

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have a diagnosis of Acute Myelogenous Leukemia (AML) according to World Health Organization (WHO) classification
• Relapsed after receiving up to 2 prior induction regimens (i.e. first or second relapse)or are refractory to not more than one prior combination chemotherapy induction regimen
• Be ≥ 55 years of age
• Have an Eastern Cooperative Oncology Group (ECOG) score of 0-2
• Be able to comply with study procedures and follow-up examinations
• Be nonfertile or agree to use birth control during the study through the end of treatment visit and for at least 90 days after the last dose of study drug
• Have adequate liver and renal function as indicated by certain laboratory values

You may not qualify if:

• Received previous treatment with clofarabine
• Received bolus, intermediate or high-dose cytarabine as induction therapy unless certain remission criteria are met
• Have received a hematopoietic stem cell transplant (HSCT) within the previous 3 months
• Have moderate or severe graft versus host disease (GVHD), whether acute or chronic
• Are receiving any other chemotherapy or investigational therapy. Patients must have been off prior AML therapy for at least 2-6 weeks prior to entering study.
• Have a psychiatric disorder that would interfere with consent, study participation, or follow-up
• Have an active, uncontrolled infection
• Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system
• Have been diagnosed with another malignancy, unless disease-free for at least 5 years; patients with treated nonmelanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed; patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease are eligible if hormonal therapy has been initiated or the malignancy has been surgically removed.
• Have clinical evidence suggestive of central nervous system (CNS) involvement with leukemia unless lumbar puncture confirms absence of leukemic blasts in the cerebrospinal fluid(CSF)
• Known HIV positivity
• Are pregnant or lactating

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (57)

Mayo Clinical Hospital

Scottsdale, Arizona, United States

Location

Arizona Cancer Center

Tucson, Arizona, United States

Location

University of Arkansas for Medical Sciences, Arkansas Cancer Research Center

Little Rock, Arkansas, United States

Location

Scripps Cancer Center

La Jolla, California, United States

Location

UCLA School of Medicine

Los Angeles, California, United States

Location

University of Southern California, Kenneth Norris Cancer Center

Los Angeles, California, United States

Location

Stanford Comprehensive Cancer Center

Stanford, California, United States

Location

University of Colorado Health Science Center

Aurora, Colorado, United States

Location

Rocky Mountain Cancer Center

Denver, Colorado, United States

Location

Cancer Center of Central Connecticut

Southington, Connecticut, United States

Location

Northwestern University

Chicago, Illinois, United States

Location

Rush University Medical Center

Chicago, Illinois, United States

Location

Evanston Northwestern Healthcare

Evanston, Illinois, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, United States

Location

University of Kentucky, Markey Cancer Center

Lexington, Kentucky, United States

Location

Louisiana State University Health Science Center

Shreveport, Louisiana, United States

Location

Harold Alfond Center for Cancer Care

Augusta, Maine, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Location

Josephine Ford Cancer Center

Detroit, Michigan, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Location

The Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States

Location

Roswell Park Cancer Center

Buffalo, New York, United States

Location

Mt. Sinai School of Medicine

New York, New York, United States

Location

New York Medical Center

Valhalla, New York, United States

Location

Mecklenburg Medical Group

Charlotte, North Carolina, United States

Location

Duke University Medical Center

Durham, North Carolina, United States

Location

Wake Forest University School of Medicine

Winston-Salem, North Carolina, United States

Location

Gabrail Cancer Center

Canton, Ohio, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Location

Oregon Health Science University

Portland, Oregon, United States

Location

Medical University of South Carolina

Charleston, South Carolina, United States

Location

University of Tennessee Medical Center

Knoxville, Tennessee, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Location

UT Southwestern Medical Center, Simmons Comprehensive Cancer Center

Dallas, Texas, United States

Location

MD Anderson Cancer Center

Houston, Texas, United States

Location

Cancer Care Centers of South Texas

San Antonio, Texas, United States

Location

University of Texas Health Sciences Center

San Antonio, Texas, United States

Location

University of Utah - Huntsman Cancer Institute

Salt Lake City, Utah, United States

Location

West Virginia University Hospitals, Mary Babb Randolph Cancer Center

Morgantown, West Virginia, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Location

Saint John Regional Hospital

Saint John, New Brunswick, Canada

Location

Juravinski Cancer Center

Hamilton, Ontario, Canada

Location

Hopital Maisonneuve-Rosemont

Montreal, Quebec, Canada

Location

Service Maladies du Sang, CHU Angers

Angers, France

Location

Hopital Claude Huriez CHRU de Lille

Lille, France

Location

Hopital Edouard Herriot

Lyon, France

Location

Institut Paoli Calmettes

Marseille, France

Location

Hopital Hotel Dieu

Nantes, France

Location

Hopital Purpan

Toulouse, France

Location

Medizinische Hochschule Hannover, Zentrum fur Innere Medizin, Abt. Haematologie / Onkologie

Hanover, Germany

Location

Medizinische Klinik der Technischen, Universität München

Munich, Germany

Location

Universitatsklinikum Ulm

Ulm, 89081, Germany

Location

Ospedali Riuniti Bergamo

Bergamo, Italy

Location

A.O Ospedale Niguarda Ca'Granda

Milan, Italy

Location

N.O. San Gerardo

Monza, Italy

Location

Azienda Ospedaliera "Antonio Cardarelli"

Napoli, Italy

Location

Related Publications (5)

• Clofarabine + Ara-c improves response rates and event-free survival, not overall survival, in older patients with relapsed/refractory AML compared to Ara-c alone: Updated CLASSIC I study results. H.M. Kantarjian, M. Wetzler, D. Rizzieri, G. J. Schiller, M. H. Jagasia, R. K. Stuart, S. Ganguly, D. Avigan, M. Craig, R. Collins, M. B. Maris, T. Kovacsovics, S. Goldberg, K. Seiter, P. Hari, J. Greiner, N. Vey, C. Recher, F. Ravandi, E.S. Wang, S. Eckert, D. Huebner and S. Faderl. Haematologica - 16th Congress of EHA Abstracts. 2011; 96(S2): 196.

  RESULT

• Clofarabine plus cytarabine compared to cytarabine alone in older patients with relapsed or refractory (R/R) acute myelogenous leukemia (AML): Results from the phase III CLASSIC 1 trial. S. Faderl, M. Wetzler, D. Rizzieri, G. J. Schiller, M. H. Jagasia, R. K. Stuart, S. Ganguly, D. Avigan, M. Craig, R. Collins, M. B. Maris, T. Kovacsovics, S. Goldberg, K. Seiter, P. Hari, F. Ravandi, E. S. Wang, S. Eckert, D. Huebner, and H. Kantarjian JCO - ASCO Meeting Abstracts. 2011; 29:6503.

  RESULT

• Faderl S, Wetzler M, Rizzieri D, Schiller G, Jagasia M, Stuart R, Ganguly S, Avigan D, Craig M, Collins R, Maris M, Kovacsovics T, Goldberg S, Seiter K, Hari P, Greiner J, Vey N, Recher C, Ravandi F, Wang ES, Vasconcelles M, Huebner D, Kantarjian HM. Clofarabine plus cytarabine compared with cytarabine alone in older patients with relapsed or refractory acute myelogenous leukemia: results from the CLASSIC I Trial. J Clin Oncol. 2012 Jul 10;30(20):2492-9. doi: 10.1200/JCO.2011.37.9743. Epub 2012 May 14.

  PMID: 22585697 RESULT

• Ganguly S, Kantarjian HM, Wetzler M, Rizzieri D, Schiller G, Jagasia M, et al. Subsequent hematopoietic stem cell transplantation (HSCT) associated with longer survival in patients with relapsed/refractory (R/R) acute myelogenous leukemia (AML) after Clo+Ara-C or Ara-C alone: a landmark analysis from the CLASSIC I trial. Biol Blood Marrow Transplant 2012;18(2Suppl):S211-S212.

  RESULT

• Ganguly S, Kantarjian HM, Wetzler M, Rizzieri D, Schiller G, Jagasia M, et al. Subsequent HSCT in the CLASSIC I Study Associated with Longer Survival in Patients With Relapsed/Refractory AML After Clo+Ara-C Or Ara-C Alone: A Landmark Analysis. Haematologica - 17th Congress of EHA Abstracts. 2012; 97(s1):32

  RESULT

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Clofarabine; Dosage Forms; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Pharmaceutical Preparations; Technology, Pharmaceutical; Investigative Techniques; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Genzyme Medical Information
• Organization: Genzyme Corporation

800-745-4447

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2006
• First Posted: April 25, 2006
• Study Start: August 1, 2006
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: April 14, 2014
• Results First Posted: September 15, 2011

Record last verified: 2014-03

Locations

US (41); CA (3); FR (6); IT (4); DE (3)