A Study of Clofarabine in Combination With Etoposide and Cyclophosphamide in Children With Acute Leukemias.

Genzyme

Status and phase: Completed; Phase 2; Phase 1

Conditions: Acute Myelogenous Leukemia; Relapsed Leukemia; Acute Lymphoblastic Leukemia

Treatments: Drug: Etoposide; Drug: clofarabine; Drug: Cyclophosphamide

Study type: Interventional

Funder types: Industry

Identifiers

NCT00315705

CLO21800205

Details and patient eligibility

About

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.

Enrollment: 50 patients

Sex: All

Ages: 1 to 21 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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50 participants in 1 patient group

clofarabine, etoposide, cyclophosphamide

Experimental group

Description:

Phase 1: escalating dosage of the three drugs delivered intravenously. Clofarabine dosage from 20-40 mg/m\^2, etoposide dosage from 75-100 mg/m\^2, cyclophosphamide dosage from 340-440 mg/m\^2. Phase 2: The recommended phase 2 doses (RP2D) were clofarabine 40 mg/m\^2, etoposide 100 mg/m\^2 and cyclophosphamide 440 mg/m\^2 delivered intravenously

Treatment:

Drug: Cyclophosphamide

Drug: clofarabine

Drug: Etoposide