OPTIM DASATINIB (Optimized Tyrosine Kinase Inhibitors Monotherapy) (OPTIM-DASA)

Versailles Hospital

Status and phase: Completed; Phase 2

Conditions: Chronic Myelogenous Leukemia, BCR/ABL Positive

Treatments: Drug: Dasatinib

Study type: Interventional

Funder types: Other

Identifiers

NCT01916785

EudraCT 2008-006854-17

Details and patient eligibility

About

This protocol is a multicentric interventional phase II study from the French CML Intergroup (FILMC).

The core of the protocol is to explore the efficacy and safety of an optimization strategy consisting in the modulation of the dasatinib daily dose according to the results of repeated plasmatic levels of dasatinib.

The objective of this strategy is to improve the overall results of the treatment of early CP-CML in order to avoid the development of resistance and BCR-ABL tyrosine kinase mutations.

The study will be conducted in selected FILMC and Canadian centers.

The study is sponsored by the Hôpitaux de Versailles and supported by Bristol-Myers Squibb. The dasatinib treatment will be provided by Bristol-Myers Squibb until marketing authorization is granted in that indication.

Enrollment: 289 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Male or female patient ≥ 18 years
2. ECOG Performance Status score 0-2
3. Philadelphia chromosome positive newly diagnosed (≤ 3 months) CP-CML
4. patients not previously treated except with hydroxyurea or imatinib (less than 4 weeks for imatinib)
5. Signed written inform consent
6. Adequate hepatic function defined as: total bilirubin ≤ 2.0 times the institutional ULN; ALT and AST ≤ 2.5 times the institutional upper limit of normal (ULN).
7. Adequate renal function defined as serum creatinine ≤ 3 times the institutional ULN.
8. Women of childbearing potential (WOCBP) must be using an adequate method of contraception.

Exclusion criteria

1. Patients with BCR-ABL positive, Philadelphia negative CML
2. Patient previously treated with a tyrosine kinase inhibitor (TKI) except with imatinib during less than 4 weeks.
3. Pregnancy
4. Active malignancy
5. Uncontrolled or significant cardiovascular disease
6. Patients with QTc > 450 ms
7. Significant bleeding disorder unrelated to CML
8. Concurrent severe diseases which exclude the administration of therapy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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289 participants in 3 patient groups

A1

Experimental group

Description:

Arm A1: Dasatinib dose adjustment based on Cmin ≥3nM value analysed on blood after 7-10 days dasatinib 100mg intake

Treatment:

Drug: Dasatinib

A2

Active Comparator group

Description:

Arm A2: Dasatinib standard dose (100mg/d) with Cmin ≥ 3nM analysed on blood after 7-10 days dasatinib 100mg intake

Treatment:

Drug: Dasatinib

B

Active Comparator group

Description:

Arm B : Dasatinib standard dose with Cmin \< 3nM analysed on blood after 7-10 days dasatinib 100mg intake

Treatment:

Drug: Dasatinib