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

NCT01534702 · Status: UNKNOWN · Phase: PHASE1/PHASE2 · Type: INTERVENTIONAL · Enrollment: 60

Last updated 2012-02-20

No results posted yet for this study

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

Interventions

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.

Sponsors & Collaborators

  • Genzyme, a Sanofi Company

    collaborator INDUSTRY

  • Hannover Medical School

    lead OTHER

Principal Investigators

  • Juergen Krauter, MD · Hannover Medical School

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2012-01-31
Primary Completion
2013-04-30
Completion
2015-09-30

Countries

  • Germany

Study Locations

More Related Trials

Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT01534702 on ClinicalTrials.gov