NCT01534702

Dose Escalation of Clofarabine in Combination With Cytarabine and Idarubicin as Induction Therapy in High Risk AML

Phase I/II Study on Cytarabine and Idarubicin Combined With Escalating Doses of Clofarabine as Induction Therapy in Patients With Acute Myeloid Leukemia and High Risk for Induction Failure (AMLSG 17-10)

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Hannover Medical School · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

With current chemotherapy protocols, in 60-80% of patients with acute myeloid leukemia (AML) the leukemic blasts in the bone marrow can be reduced to \< 5%. This is called "complete remission (CR)" and is the prerequisite for cure of the disease. During the last years, several genetic and biologic risk factors for the achievement of CR have been defined, and the remission rates vary considerably between patient groups with different risk profiles. On one hand, patients with certain chromosomal or molecular aberrations have very high CR rates of approximately 90%. Moreover, in some of these patients, molecularly targeted therapies for specific genetic aberrations are currently evaluated in clinical trials. However, these genetic aberrations account for only 50-60% of the overall patient population in AML. The remaining patients have a significantly inferior CR rate of only 50-60% with 30% resistant disease after two cycles of standard induction chemotherapy. In conclusion, there is need for improved induction regimens in a large number of adult patients with AML. An improved CR rate in this patient population will increase the number of patients eligible for intensive consolidation such as an allogeneic stem cell transplantation and might thereby be the basis for a better overall outcome. However, there is no clear evidence that this goal can be achieved with the currently available chemotherapy protocols. Clofarabine (2-chloro-2-fluoro-deoxy-9-D-arabinofuranosyladenine) is a nucleoside analogon which combines properties of fludarabine and cladribine. Due to the lack of neurological side effects, clofarabine could be explored in higher doses than other nucleoside analogues and has shown considerable antileukemic activity in patients with relapsed or refractory acute leukemias and elderly AML patients alone or in combination with cytarabine. In addition, the combination of clofarabine, cytarabine and idarubicin has produced promising results with acceptable toxicity in patients with relapsed or refractory AML. Based on these initial studies, there is need for a further optimization of the clofarabine dose in this combination. The aim of the AMLSG 17-10 study is therefore to evaluate the tolerability and safety of increasing doses of clofarabine in combination with idarubicin/cytarabine in patients with high risk AML defined by the genetic and molecular risk profile.

Conditions

• Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	clofarabine, cytarabine, idarubicin	Treatment is stratified according to patients age (\< 60 years vs. ≥ 60 years). Medication: Patients \< 60 years: * idarubicin 7.5 mg/m2 iv, days 1 + 3 * cytarabine 750 mg/m2 iv, days 1 to 5 Patients ≥ 60 years: * idarubicine 6 mg/m2 iv, days 1 + 3 * cytarabine 750 mg/m2 iv, days 1 to 5 Clofarabine will be given in escalating doses to cohorts of at least three patients: Clofarabine: * level -1: 15 mg/m2 iv, days 1 to 5 * level 1: 20 mg/m2 iv, days 1 to 5 * level 2: 25 mg/m2 iv, days 1 to 5 * level 3: 30 mg/m2 iv, days 1 to 5 * level 4: 35 mg/m2 iv, days 1 to 5 Patients will be recruited according to a 3+3 design. New cohorts will be initiated depending on toxicity of the previous cohort during the first induction cycle. Enrollment will begin with dose level 1.

Timeline

• Start date: 2012-01-01
• Primary completion: 2013-04-01
• Completion: 2015-09-01
• First posted: 2012-02-17
• Last updated: 2012-02-20

Locations

7 sites across 1 country: Germany