Clinical trial NCT00315705: A Study of Clofarabine in Combination With Etoposide and Cyclophosphamide in Children With Acute Leukemias.
Official title: A Phase 1/2 Dose-Escalation Study of Clofarabine in Combination With Etoposide and Cyclophosphamide in Pediatric Patients With Refractory or Relapsed Acute Leukemias.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Acute Lymphoblastic Leukemia
Acute Myelogenous Leukemia
Relapsed Leukemia
Keywords: clofarabine
acute leukemia
ALL
AML
clolar
CLO218
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2006-04-19
Enrollment: 50
Sex: ALL
Minimum age (years): 1
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 or refractory acute lymphoblastic leukemia (ALL) who have had at least 2 prior treatment regimens. This use is based on the induction of complete responses. Randomized trials demonstrating increased survival or other clinical benefit have not been conducted.

The purpose of the phase 1 portion of this study was to determine if clofarabine added to a combination of etoposide and cyclophosphamide is safe in children with relapsed or refractory acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML). The purpose of the phase 2 portion of the study was to measure the effectiveness of the combination therapy in children with ALL.


Eligibility criteria: Inclusion Criteria:

* NOTE: the following eligibility criteria were applicable to acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML) patients for the Phase 1 portion of this study, and to ALL patients for the Phase 2 portion of the study (only ALL patients were allowed in the Phase 2 portion of the study).
* ALL with \> 25% blasts in bone marrow; AML with ≥ 5% blasts in bone marrow; ALL and AML patients may have extramedullary disease
* Karnofsky Performance Status ≥ 50 for patients \> 10 years old; Lansky Performance Status ≥ 50 for patients ≤ 10 years old
* Prior therapy: AML: 1-2 prior induction regimens and ≤ 1 hematopoietic stem cell transplant (HSCT); ALL: 1-3 prior induction regimens
* Adequate liver, renal, pancreatic, and cardiac function
* Have received no prior HSCT (study amended in Phase 2 to exclude patients with prior HSCT)

Exclusion Criteria:

* NOTE: the following eligibility criteria were applicable to ALL and AML patients for the Phase 1 portion of this study, and to ALL patients for the Phase 2 portion of the study (only ALL patients were allowed in the Phase 2 portion of the study).
* Burkitt's leukemia
* Previous treatment with clofarabine
* Uncontrolled systemic fungal, bacterial or other infection and 48 hrs negative blood cultures required for patients with a history of fever within 3 days of enrollment
* Active CNS involvement (i.e., should be CNS1 or CNS2)
* Inadequate time since last therapy: ≤ 14 days since last cytotoxic chemotherapy; ≤ 7 days since last biologic therapy; ≤ 14 days since last monoclonal antibody therapy
* Have received prior HSCT (study amended in Phase 2 to exclude patients with prior HSCT)
* Pregnant or lactating
* Have tested positive for hepatitis B or hepatitis C infection or history of cirrhosis

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) in Phase 1
timeFrame: Up to Day 42 (Phase 1 portion of study)
measure: Participants With Dose Limiting Toxicity in Phase 1
timeFrame: Up to Day 42 (Phase 1 portion of study)
measure: Percentage of Participants Achieving A Response Over the First Two Treatment Cycles in Phase 2
timeFrame: Approximately 28-56 days (Phase 2 portion of study)
Secondary outcomes:
measure: Summary of Participants With Adverse Events (AEs) in Phase 1
timeFrame: Up to 9.5 months (Phase 1 portion of study)
measure: Percentage of Participants Achieving A Response Over the First Two Treatment Cycles in Phase 1
timeFrame: Approximately 2 months (Phase 1 portion of study)
measure: Time to Remission for Participants Who Had a Response in Phase 1
timeFrame: up to 8 weeks (Phase 1 portion of study)
measure: Kaplan Meier Estimate of Duration of Remission (DOR) for Participants Who Achieved Overall Remission (OR) in Phase 1
timeFrame: Up to 2 years (Phase 1 portion of study)
measure: Kaplan Meier Estimates of Event-free Survival (EFS) for Participants in Phase 1
timeFrame: Up to 2 years (Phase 1 portion of study)
measure: Number of Participants With 4-month Event Free Survival in Phase 1
timeFrame: 4 months (Phase I portion of study)
measure: Kaplan Meier Estimates of Overall Survival (OS) for Participants in Phase 1
timeFrame: Up to 2 years (Phase 1 portion of study)
measure: Summary of Participants With Adverse Events (AEs) in Phase 2
timeFrame: Up to 9.5 months (Phase 2 portion of study)
measure: Time to Remission for Participants Who Had a Response in Phase 2
timeFrame: up to 8 weeks (Phase 2 portion of study)
measure: Kaplan Meier Estimate of Duration of Remission (DOR) for Participants Who Achieved Overall Remission (OR) in Phase 2
timeFrame: Up to 2 years (Phase 2 portion of study)
measure: Kaplan Meier Estimates of Event-free Survival (EFS) for Participants in Phase 2
timeFrame: Up to 2 years (Phase 2 portion of study)
measure: Number of Participants With 4-month Event Free Survival in Phase 2
timeFrame: 4 months (Phase 2 portion of study)
measure: Kaplan Meier Estimates of Overall Survival (OS) for Participants in Phase 2
timeFrame: Up to 2 years (Phase 2 portion of study)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's Hospital of Alabama
state: Alabama
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital
state: California
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: Indianapolis
country: United States
facility: St. Vincent Children's Hospital
state: Indiana
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: New York School of Medicine
state: New York
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
affiliation: Genzyme, a Sanofi Company
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Hijiya N, Thomson B, Isakoff MS, Silverman LB, Steinherz PG, Borowitz MJ, Kadota R, Cooper T, Shen V, Dahl G, Thottassery JV, Jeha S, Maloney K, Paul JA, Barry E, Carroll WL, Gaynon PS. Phase 2 trial of clofarabine in combination with etoposide and cyclophosphamide in pediatric patients with refractory or relapsed acute lymphoblastic leukemia. Blood. 2011 Dec 1;118(23):6043-9. doi: 10.1182/blood-2011-08-374710. Epub 2011 Oct 3.