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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT00317642
First received: April 24, 2006
Last updated: March 17, 2014
Last verified: March 2014
Results First Received: August 11, 2011  
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
Condition: Acute Myelogenous Leukemia
Interventions: Drug: clofarabine (IV formulation)
Drug: placebo
Drug: cytarabine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
352 patients screened and 326 randomized, 163 to each treatment group. One participant withdrew after being randomized to the Placebo and Cytarabine Group and was excluded from efficacy analysis.

Reporting Groups
  Description
Clofarabine (IV Formulation) and Cytarabine Participants received clofarabine 40 mg/m^2 administered as a 1-hour intravenous (IV) infusion, followed 3 hours later (from end of infusion) by cytarabine 1 g/m^2 administered as a 2-hour IV infusion for 5 days (induction and re-induction) or 4 days (consolidation). Participants could receive up to 3 cycles of treatment: induction, re-induction (if the participant had not achieved remission following induction but hematological improvement was noted), and consolidation.
Placebo and Cytarabine Participants received placebo (sodium chloride) administered as a 1-hour IV infusion, followed 3 hours later (from end of infusion) by cytarabine 1 g/m^2 administered as a 2-hour IV infusion for 5 days (induction and re-induction) or 4 days (consolidation). Participants could receive up to 3 cycles of treatment: induction, re-induction, and consolidation.

Participant Flow:   Overall Study
    Clofarabine (IV Formulation) and Cytarabine     Placebo and Cytarabine  
STARTED     163     163  
Full Analysis Set     162 [1]   158 [1]
Received >= 1 Study Drug (Safety Set)     161     155  
COMPLETED     41 [2]   28 [2]
NOT COMPLETED     122     135  
Not Received Either Study Drug                 1                 3  
Physician Decision                 15                 7  
Participant declined treatment                 14                 3  
Adverse Event                 17                 5  
Treatment Failure                 56                 102  
Disease Recurrence                 1                 2  
Death                 14                 7  
Not Continue to Consolidation                 2                 0  
Withdrawal by Subject                 0                 1  
Referred For Transplantation                 1                 0  
AML Not Centrally Confirmed                 1                 5  
[1] AML Centrally Confirmed
[2] achieved remission and completed consolidation



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Clofarabine (IV Formulation) and Cytarabine Participants received clofarabine 40 mg/m^2 administered as a 1-hour intravenous (IV) infusion, followed 3 hours later (from end of infusion) by cytarabine 1 g/m^2 administered as a 2-hour IV infusion for 5 days (induction and re-induction) or 4 days (consolidation). Participants could receive up to 3 cycles of treatment: induction, re-induction (if the participant had not achieved remission following induction but hematological improvement was noted), and consolidation.
Placebo and Cytarabine Participants received placebo (sodium chloride) administered as a 1-hour IV infusion, followed 3 hours later (from end of infusion) by cytarabine 1 g/m^2 administered as a 2-hour IV infusion for 5 days (induction and re-induction) or 4 days (consolidation). Participants could receive up to 3 cycles of treatment: induction, re-induction, and consolidation.
Total Total of all reporting groups

Baseline Measures
    Clofarabine (IV Formulation) and Cytarabine     Placebo and Cytarabine     Total  
Number of Participants  
[units: participants]
  162     158     320  
Age  
[units: years]
Mean ± Standard Deviation
  67.0  ± 6.36     67.1  ± 5.82     67.0  ± 6.09  
Gender  
[units: participants]
     
Female     48     57     105  
Male     114     101     215  
Ethnicity (NIH/OMB)  
[units: participants]
     
Hispanic or Latino     9     6     15  
Not Hispanic or Latino     153     152     305  
Unknown or Not Reported     0     0     0  
Race (NIH/OMB)  
[units: participants]
     
American Indian or Alaska Native     0     0     0  
Asian     3     2     5  
Native Hawaiian or Other Pacific Islander     0     0     0  
Black or African American     7     11     18  
White     150     142     292  
More than one race     0     0     0  
Unknown or Not Reported     2     3     5  
Height (cm)  
[units: centimeter]
Mean ± Standard Deviation
  171.5  ± 10.27     170.5  ± 8.92     171.0  ± 9.62  
Weight(kg)  
[units: kg]
Mean ± Standard Deviation
  81.21  ± 17.862     83.03  ± 17.281     82.11  ± 17.574  
Body Surface Area (BSA)  
[units: m^2]
Mean ± Standard Deviation
  1.941  ± 0.2383     1.959  ± 0.2338     1.950  ± 0.2359  
Eastern Cooperative Oncology Group Performance Status [1]
[units: Participants]
     
ECOG 0     57     48     105  
ECOG 1     79     92     171  
ECOG 2     26     18     44  
Karyotype [2]
[units: participants]
     
Favorable     1     0     1  
Intermediate     65     84     149  
Unfavorable     86     70     156  
Not Assessed     8     3     11  
unknown     2     1     3  
[1] Eastern Cooperative Oncology Group Performance Status (ECOG PS) is a scale ranging from 0-5, with 0 (fully active); 1 (capable of light work); 2 (no work but all self-care); 3 (limited self-care); 4 (completely disabled); 5 (dead).
[2] Favorable karyotype was defined as any abnormality of chromosome 16; Intermediate karyotype was defined as normal (no abnormalities); Unfavorable karyotype was defined as any other abnormality



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Overall Survival – Overall and by Calculated Strata (CSR 7-April-11)   [ Time Frame: Day 1 (randomization) up to approximately 4 years ]

2.  Primary:   Overall Survival - Overall and by Randomized Strata (CSR 9-July-12)   [ Time Frame: Day 1 (randomization) up to approximately 4 years ]

3.  Secondary:   Best Response Per Independent Response Review Panel (IRRP) Assessment – Overall and by Calculated Strata (CSR 7-April-11)   [ Time Frame: Day 12 up to approximately 6 months ]

4.  Secondary:   Duration of Remission (DOR) Per IRRP Assessment-Overall and by Calculated Strata (CSR 7-April-11)   [ Time Frame: Day 12 to approximately 4 years ]

5.  Secondary:   Duration of Remission (DOR) Per IRRP Assessment-Overall and by Randomized Strata (CSR 9-July-12)   [ Time Frame: Day 12 to approximately 4 years ]

6.  Secondary:   Disease-free Survival by IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11)   [ Time Frame: Day 12 to approximately 4 years ]

7.  Secondary:   Disease-free Survival by IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12)   [ Time Frame: Day 12 to approximately 4 years ]

8.  Secondary:   Event-free Survival by IRRP Assessment – Overall and by Calculated Strata (CSR 7-April-11)   [ Time Frame: Day 1 (randomization) up to approximately 4 years ]

9.  Secondary:   Event-free Survival by IRRP Assessment – Overall and by Randomized Strata (CSR 9-July-12)   [ Time Frame: Day 1 (randomization) up to approximately 4 years ]

10.  Secondary:   Four-Month Event-free Survival Per IRRP Assessment – Overall and by Calculated Strata (CSR 7-April-11)   [ Time Frame: Day 1 (randomization) to Day 122 ]

11.  Secondary:   Four-Month Event-free Survival Per IRRP Assessment – Overall and by Randomized Strata (CSR 9-July-12)   [ Time Frame: Day 1 (randomization) to Day 122 ]

12.  Secondary:   Participants With Adverse Events (CSR 7-April-11)   [ 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.) ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Genzyme Medical Information
Organization: Genzyme Corporation
phone: 800-745-4447


Publications of Results:
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.
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


Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
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: March 17, 2014
Health Authority: United States: Food and Drug Administration
Italy: Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Canada: Health Canada