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

Sponsor:	Genzyme
Information provided by:	Genzyme
ClinicalTrials.gov Identifier:	NCT00317642

Purpose

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.

Condition	Intervention	Phase
Acute Myelogenous Leukemia	Drug: clofarabine (IV formulation) Drug: placebo Drug: cytarabine	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Phase III Randomized, Double-blind, Controlled Study Comparing Clofarabine and Cytarabine Versus Cytarabine Alone in Adult Patients 55 Years and Older With Acute Myelogenous Leukemia (AML) Who Have Relapsed or Are Refractory After Receiving up to Two Prior Induction Regimens

Resource links provided by NLM:

MedlinePlus related topics: Acute Myeloid Leukemia Leukemia

Drug Information available for: Cytarabine hydrochloride Clofarabine Cytarabine

U.S. FDA Resources

Further study details as provided by Genzyme:

Primary Outcome Measures:

Overall Survival [ Time Frame: Day 1 (randomization) up to approximately 4 years ] [ Designated as safety issue: No ]
Overall survival (OS) for Full Analysis Set (FAS) and for the 2 randomization strata - Participants with CR1 <6 months and Participants with CR1 >=6 months (CR1 = remission after first pre-study induction regimen) - was defined as the number of months from date of randomization until date of death due to any cause.

Secondary Outcome Measures:

Best Response Per Independent Response Review Panel (IRRP) Assessment - Overall and by Randomization Strata [ Time Frame: Day 12 up to approximately 6 months ] [ Designated as safety issue: No ]
Percentage of participants in each treatment arm whose best response was assessed by the IRRP as CR or CRi. CR is defined as complete remission. CRi is complete remission with incomplete peripheral blood count. Overall Remission (OR) rate is also presented, defined as CR+CRi.
Duration of Remission Per IRRP Assessment-Overall and by Randomization Strata [ Time Frame: Day 12 to approximately 4 years ] [ Designated as safety issue: No ]
Duration of Remission was defined as the time from first CR or CRi to the date of first objective documentation of disease recurrence, initiation of alternative antileukemic therapy [including hematopoietic stem cell transplant (HSCT)] while in remission, or death due to any cause, whichever occurred first. CR is defined as complete remission. CRi is complete remission with incomplete peripheral blood count.
Disease-free Survival by IRRP Assessment - Overall and by Randomization Strata [ Time Frame: Day 12 to approximately 4 years ] [ Designated as safety issue: No ]
Disease-free survival was defined as the time from first CR or CRi until the date of first objective documentation of disease recurrence or death due to any cause, whichever occurred first. CR is defined as complete remission. CRi is complete remission with incomplete peripheral blood count.
Event-free Survival by IRRP Assessment - Overall and by Randomization Strata [ Time Frame: Day 1 (randomization) up to approximately 4 years ] [ Designated as safety issue: No ]
Event-free survival (EFS) was defined as the time from randomization to the date of treatment failure, first disease recurrence (for participants who achieved remission), or death due to any cause, whichever occurred first. Treatment Failure - ≥5% leukemic blasts by BM exam, with no evidence of hematologic response (ie, <30% decrease in % leukemic blasts); Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease
Four-Month Event-free Survival (EFS) Per IRRP Assessment - Overall and by Randomization Strata (FAS) [ Time Frame: Day 1 (randomization) to Day 122 ] [ Designated as safety issue: No ]
Four-month EFS was defined as achieving an EFS of at least 122 days, where EFS is defined as the time from randomization to the date of treatment failure, first disease recurrence (for participants who achieved remission), or death due to any cause, whichever occurred first.
Participants With Adverse Events [ Time Frame: Day 1 up to a maximum of 4 years (includes up to a maximum of 3 cycles of therapy plus 45 days follow up. Related AEs are followed to resolution.) ] [ Designated as safety issue: Yes ]
Number of participants with treatment emergent adverse events (TEAEs) or death due to related AE. Related AEs for the combination arm can be related to either clofarabine or cytarabine.

Grade 1 = Mild AE, Grade 2 = Moderate AE, Grade 3 = Severe AE, Grade 4 = Life Threatening AE, Grade 5 = Death

Enrollment:	326
Study Start Date:	August 2006
Estimated Study Completion Date:	January 2012
Primary Completion Date:	August 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: clofarabine (IV formulation) and cytarabine 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) clofarabine (IV formulation) infusion 40mg/m^2 / day up to 3 cycles Drug: cytarabine cytarabine IV infusion 1g/m^2/day for up to 3 cycles
Experimental: placebo and cytarabine 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 placebo (sodium Chloride) 1-hour IV infusion Drug: cytarabine cytarabine IV infusion 1g/m^2/day for up to 3 cycles

Arms

Assigned Interventions

Experimental: clofarabine (IV formulation) and cytarabine

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)

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

Drug: cytarabine

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

Experimental: placebo and cytarabine

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

placebo (sodium Chloride) 1-hour IV infusion

Drug: cytarabine

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

Eligibility

Ages Eligible for Study:	55 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00317642

Show 57 Study Locations

Sponsors and Collaborators

Genzyme

Investigators

Study Director:

Medical Monitor

Genzyme

More Information

No publications provided

Responsible Party:	Medical Monitor, Genzyme Corporation
ClinicalTrials.gov Identifier:	NCT00317642 History of Changes
Other Study ID Numbers:	CLO34100405, 2008-001043-19
Study First Received:	April 24, 2006
Results First Received:	August 11, 2011
Last Updated:	November 23, 2011
Health Authority:	United States: Food and Drug Administration; Italy: Ministry of Health; Germany: Federal Institute for Drugs and Medical Devices; France: Afssaps - French Health Products Safety Agency; Canada: Health Canada

Keywords provided by Genzyme:

acute myelogenous leukemia
acute myeloid leukemia
relapsed AML
refractory AML

clofarabine
cytarabine
CLO341
clolar

Additional relevant MeSH terms:

Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Clofarabine
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 February 09, 2012