Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Cytarabine

Clofarabine

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

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

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)

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

clofarabine (IV formulation)

placebo (sodium Chloride) 1-hour IV infusion

placebo

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

cytarabine

Medical Monitor

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.

After screening and eligibility assessment, patients were randomized (in a 1:1 ratio) to receive either clofarabine or matching placebo, in addition to cytarabine. Randomization was stratified by remission status following the first induction regimen (CR1): no remission \[i.e., CR1 = refractory\] or remission \<6 months vs remission ≥6 months. During randomization by interactive voice response system (IVRS), there were 10 participants misclassified to the CR1 \<6 months stratum and 12 participants misclassified to CR1 ≥6 months stratum. The error did not affect the participants' treatment, only the stratification. Due to the misclassification, outcomes that used strata in their analysis were analyzed twice: once with the 'randomized stratification' which includes the misclassification and once with the 'calculated stratification' in which participants appear in the 'correct' strata.

Two clinical study reports were written for this study.

1. Clinical study report dated 7 April 2011 includes the entire treatment period of all participants plus much of the follow-up. At that time, 33 participants in the Clofarabine+cytarabine group and 29 participants in the placebo+cytarabine group were still being follow-up post treatment. Results were reported on clinicaltrials.gov in August 2011. Outcomes that used strata reported the 'calculated strata' on clinicaltrials.gov.
2. Clinical study report dated 9 July 2012 includes all patient treatment experience plus all long-term follow-up (a minimum of 2 years from the end of treatment or until the patient died). The study was completed at that time. Outcomes that used strata reported the 'randomized strata' on clinicaltrials.gov. AE records on clinicaltrials.gov reflect the final database.

Outcomes that changed between the two clinical study reports due to the additional long-term follow-up data are reported twice on clinicaltrials.gov (once from each clinical study report) and the appropriate report date is included in the outcome description. Outcomes from the 9 July 2012 report represent more complete data.

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

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

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.

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.

Percentage of participants whose best response was assessed by the IRRP as complete remission (CR) or complete remission with incomplete peripheral blood count recovery (CRi) using the revised International Working Group for Response Criteria (Cheson 2003).

CR is defined on morphologic criteria at a single response assessment:

* a bone marrow aspirate or biopsy of \<5% blasts, with evidence of normal hematopoiesis;
* absence of Auer rods in the blasts that are present;
* absence of extramedullary disease;
* absence of a unique phenotype determined at the pretreatment specimen, as assessed by immunophenotyping;
* only rare evidence of circulating blasts. If present, evidence of a regenerating bone marrow;
* recovery of peripheral counts (platelets ≥100\*10\^9/L and absolute neutrophil count (ANC) ≥1.0\*10\^9/L).

CRi met all criteria for CR except for either residual neutropenia (ANC \<1.0\*10\^9/L) or thrombocytopenia (platelet count \<100\*10\^9/L).

DOR 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 \[including hematopoietic stem cell transplant\] while in remission, or death due to any cause, whichever occurred first.

CR is defined on morphologic criteria at a single response assessment:

* a bone marrow aspirate or biopsy of \<5% blasts, with evidence of normal hematopoiesis;
* absence of Auer rods in the blasts that are present;
* absence of extramedullary disease;
* absence of a unique phenotype determined at the pretreatment specimen, as assessed by immunophenotyping;
* only rare evidence of circulating blasts. If present, evidence of a regenerating bone marrow;
* recovery of peripheral counts (platelets ≥100\*10\^9/L and absolute neutrophil count (ANC) ≥1.0\*10\^9/L).

CRi met all criteria for CR except for either residual neutropenia (ANC \<1.0\*10\^9/L) or thrombocytopenia (platelet count \<100\*10\^9/L).

Disease-free survival was defined as the time from first complete remission (CR) or complete remission with incomplete peripheral blood count recovery (CRi) until the date of first objective documentation of disease recurrence or death due to any cause, whichever occurred first.

See Outcome #3 for definition of CR and CRi.

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.

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 bone marrow 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) 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.

Treatment Failure - ≥5% leukemic blasts by bone marrow 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.

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

Genzyme, a Sanofi Company

In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables. Adverse event information is from the final database supporting the clinical study report dated 9-July-12.

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.

Clofarabine (IV Formulation) 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.

Placebo and Cytarabine

Overall

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Height (cm)

Weight(kg)

Body Surface Area (BSA)

ECOG 0

ECOG 1

ECOG 2

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).

Eastern Cooperative Oncology Group Performance Status

Favorable

Intermediate

Unfavorable

Not Assessed

unknown

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

Karyotype

Genzyme Medical Information

Participants stratified by calculated strata remission after first pre-study induction regimen (CR1) \< 6 months

Participants stratified by calculated strata CR1\>= 6 months

Clofarabine (IV Formulation) and Cytarabine (FAS)

Placebo and Cytarabine (FAS)

Clofarabine and Cytarabine - In Stratum < 6 Months

Placebo and Cytarabine - In Stratum < 6 Months

Clofarabine and Cytarabine In Stratum >= 6 Months

Placebo and Cytarabine In Stratum >= 6 Months

Full Analysis Set (FAS)-all randomized participants whose baseline AML diagnosis was centrally confirmed. Strata are calculated according to duration of the first remission based on case report forms (CRF) data and do not include the IVRS mistakes. One participant's strata (placebo group) could not be calculated so the participant was excluded.

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

Full Analysis Set (FAS) population - overall remission (OR)

Full Analysis Set (FAS) population - Complete Remission (CR)

Participants stratified by calculated strata - CR1 \<6 months \[Overall Remission (CR+CRi)\]

Participants stratified by calculated strata - CR1 \>=6 months \[Overall Remission (CR+CRi)\]

Participants stratified by calculated strata - CR1 \<6 months \[Complete Remission (CR)\]

Participants stratified by calculated strata - CR1 \>=6 months \[Complete Remission (CR)\]

Overall Remission (CR + CRi)

Complete Remission (CR)

CR with incomplete blood count recovery (CRi)

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

Participants in the FAS who achieved OR (CR + CRi). Strata are calculated according to duration of the first remission based on case report forms (CRF) data and do not include the IVRS mistakes.

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

Participants in the FAS who achieved OR (CR + CRi). Strata are as randomized by the IVRS, therefore strata include the IVRS mistakes.

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

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

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

Participants stratified by randomization strata CR1 \<6 months

Participants stratified by randomization strata CR1 \>=6 months

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

Full Analysis Set (FAS) - composed of all randomized participants whose baseline AML diagnosis was centrally confirmed. Strata are as randomized by the IVRS, therefore strata include the IVRS mistakes.

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

Full Analysis Set - composed of all randomized participants whose baseline AML diagnosis was centrally confirmed. Strata are as randomized by the IVRS, therefore strata include the IVRS mistakes.

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

Participants stratified by randomization strata CR1 \<6 months.

Four-Month Event-free Survival Per IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11)

Full Analysis Set - composed of all randomized participants whose baseline AML diagnosis was centrally confirmed. Strata are as randomized by the IVRS, that is the strata include the IVRS mistakes.

Four-Month Event-free Survival Per IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12)

Any Treatment Emergent AE

Any Related Treatment Emergent AE

Any Treatment Emergent Grade >=3 AE

Any Related Treatment Related Grade >=3 AE

Discontinue of study medication due to AE

Discontinue of study medication due to related AE

Safety Set - Participants in the Full Analysis Set (FAS) who received at least 1 dose of study drug.

Participants With Adverse Events (CSR 7-April-11)

Overall Study

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 lymphoblastic leukemia (ALL) who have had at least 2 prior treatment regimens.

This is a single arm, open-label, Phase II study of CLOFARABINE in adult patients with refractory or relapsed acute myelogenous leukemia (AML). Qualified patients must be refractory to one or two induction regimens, or have relapsed \< one year from the date of confirmation of the initial complete remission (CR). There will be two phases in this study - an Induction phase and a Consolidation phase.

Phase II Study of Clofarabine in Adult Patients With Refractory or Relapsed Acute Myelogenous Leukemia

A Phase II, Open-Label Study of Clofarabine in Adult Patients With Refractory or Relapsed Acute Myelogenous Leukemia

Symptoms and General Pathology

Immune System Diseases

Syndrome

Preleukemia

Myelodysplastic Syndromes

Leukemia, Lymphoid

Lymphoma

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Bone Marrow Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Childhood Acute Lymphoblastic Leukemia

Lymphosarcoma

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

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 lymphoblastic leukemia (ALL) who have had at least 2 prior treatment regimens.

This research study of clofarabine will be used for advanced cancer in persons in which drugs are no longer effective or no reliable effective treatment is available. The purpose of this study is to find the answers to the following research questions:

1. What is the largest dose of clofarabine that can be safely administered as an IV infusion (over at least 2 hours) once a week for 3 weeks (days 1, 8 and 15) followed by 1 week of rest and repeated every 28 days?
2. What are the side effects of clofarabine when given on this schedule?
3. How much clofarabine is in the blood at specific times after administration and how does the body get rid of the drug? Once the MTD/RP2D is established, patients will be enrolled at the MTD/RP2D regardless of the PK data with cardiac assessments done every other cycle.
4. Will clofarabine help treat a specific cancer?

Clofarabine in Adult Patients With Advanced Solid Tumors

A Phase I and Pharmacokinetic Study of Clofarabine in Adult Patients With Advanced Solid Tumors

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 lymphoblastic leukemia (ALL) who have had at least 2 prior treatment regimens.

The purpose of this study is to determine whether Clofarabine is safe and effective in the treatment of Acute Lymphoblastic Leukemia (ALL.)

This is a non-randomized, open label, Phase II study of Clofarabine in pediatric patients with refractory or relapsed acute lymphoblastic leukemia (ALL). Eligible patients must be in second or subsequent relapse or be refractory. Forty eligible patients will be enrolled in a Fleming 2-stage sequential study design in order to better assess the efficacy and safety of clofarabine in this patient population.

Phase II Study of Clofarabine in Pediatric Acute Lymphoblastic Leukemia (ALL)

A Phase II, Open Label Study of Clofarabine in Pediatric Patients With Refractory or Relapsed Acute Lymphoblastic Leukemia

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 lymphoblastic leukemia (ALL) who have had at least 2 prior treatment regimens.

The purpose of this study is to determine whether Clofarabine is safe and effective in the treatment of Acute Myelogenous Leukemia (AML.)

This is a non-randomized, open label, Phase II study of Clofarabine in pediatric patients with refractory or relapsed acute myelogenous leukemia (AML). Eligible patients must be in first or subsequent relapse or be refractory. Forty eligible patients will be enrolled in a Fleming 2-stage sequential study design in order to better assess the efficacy and safety of clofarabine in this patient population.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Clofarabine and Cytarabine for Older Patients With Relapsed or Refractory Acute Myelogenous Leukemia (AML)(CLASSIC I)	NCT00317642	Acute Myelogeno...	clofarabine (IV... placebo cytarabine	55 Years -	Sanofi
Phase II Study of Clofarabine in Adult Patients With Refractory or Relapsed Acute Myelogenous Leukemia	NCT00044889	Acute Myelogeno...	clofarabine (IV...	18 Years -	Sanofi
Clofarabine in Adult Patients With Advanced Solid Tumors	NCT00125840	Solid Tumors Leukemia, Lymph... Leukemia, Lymph... Leukemia, Myelo... Leukemia, Myelo... Myelodysplastic...	clofarabine (IV...	18 Years -	Sanofi
Clofarabine in Adult Patients With Advanced Solid Tumors	NCT00125840	Solid Tumors Leukemia, Lymph... Leukemia, Lymph... Leukemia, Myelo... Leukemia, Myelo... Myelodysplastic...	clofarabine (IV...	18 Years -	Sanofi
A Study of Clofarabine and Cytarabine for Older Patients With Relapsed or Refractory Acute Myelogenous Leukemia (AML)(CLASSIC I)	NCT00317642	Acute Myelogeno...	clofarabine (IV... placebo cytarabine	55 Years -	Sanofi
Clofarabine in Adult Patients With Advanced Solid Tumors	NCT00125840	Solid Tumors Leukemia, Lymph... Leukemia, Lymph... Leukemia, Myelo... Leukemia, Myelo... Myelodysplastic...	clofarabine (IV...	18 Years -	Sanofi
Phase II Study of Clofarabine in Pediatric Acute Lymphoblastic Leukemia (ALL)	NCT00042341	Leukemia, Lymph...	clofarabine (IV...	- 21 Years	Sanofi
Phase II Study of Clofarabine in Pediatric Acute Myelogenous Leukemia (AML) Patients	NCT00042354	Leukemia, Myelo...	clofarabine (IV...	- 21 Years	Sanofi

Spots Global Cancer Trial Database for clofarabine (iv formulation)