Dasatinib Combination Therapy With the Smoothened (SMO) Inhibitor BMS-833923 in Chronic Myeloid Leukemia (CML)

NCT ID: NCT01218477

Last Updated: 2016-06-17

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

33 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-01-31

Study Completion Date

2013-04-30

Brief Summary

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The purpose of the study is to determine the safety and tolerability of the combination of BMS-833923 plus dasatinib in patients with chronic myeloid leukemia.

Detailed Description

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Conditions

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Leukemia

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dasatinib, 100/140 mg QD

Participants received dasatinib, 100/140 mg once daily (QD), depending on cohort (100 mg for those with chronic myeloid leukemia \[CML\]-chronic phase; 140 mg for those with CML-advanced phase)

Group Type EXPERIMENTAL

Dasatinib

Intervention Type DRUG

Oral tablets, 100-140 mg once daily, depending on cohort (100 mg for those with chronic myeloid leukemia \[CML\]-chronic phase; 140 mg for those with CML-advanced phase)

Dasatinib, 100/140 mg QD + BMS-833923, 50 mg QD

Participants received dasatinib, 100/140 mg once daily (QD), depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase) plus BMS-833923, 50 mg, QD

Group Type EXPERIMENTAL

Dasatinib

Intervention Type DRUG

Oral tablets, 100-140 mg once daily, depending on cohort (100 mg for those with chronic myeloid leukemia \[CML\]-chronic phase; 140 mg for those with CML-advanced phase)

BMS-833923

Intervention Type DRUG

Oral capsules, 50-200 mg, depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)

Dasatinib, 100/140 mg QD + BMS-833923, 100 mg BID/QD

Participants received BMS-833923, 100 mg twice daily (BID) for 7 days then once daily (QD) + dasatinib, 100/140 mg QD, depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)

Group Type EXPERIMENTAL

Dasatinib

Intervention Type DRUG

Oral tablets, 100-140 mg once daily, depending on cohort (100 mg for those with chronic myeloid leukemia \[CML\]-chronic phase; 140 mg for those with CML-advanced phase)

BMS-833923

Intervention Type DRUG

Oral capsules, 50-200 mg, depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)

Dasatinib, 100 /140 mg QD+ BMS-833923, 200 mg BID/QD

Participants received BMS-833923, 200 mg twice daily (BID) for 7 days then 200 mg once daily (QD) plus dasatinib, 100 /140 mg QD), depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)

Group Type EXPERIMENTAL

Dasatinib

Intervention Type DRUG

Oral tablets, 100-140 mg once daily, depending on cohort (100 mg for those with chronic myeloid leukemia \[CML\]-chronic phase; 140 mg for those with CML-advanced phase)

BMS-833923

Intervention Type DRUG

Oral capsules, 50-200 mg, depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)

Interventions

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Dasatinib

Oral tablets, 100-140 mg once daily, depending on cohort (100 mg for those with chronic myeloid leukemia \[CML\]-chronic phase; 140 mg for those with CML-advanced phase)

Intervention Type DRUG

BMS-833923

Oral capsules, 50-200 mg, depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)

Intervention Type DRUG

Other Intervention Names

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Sprycel

Eligibility Criteria

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Inclusion Criteria

* Age ≥18 years
* Diagnosis of chronic myeloid leukemia (CML) and cytogenetic positive for the Philadelphia chromosome (Ph+), documented Ph+ cells on bone marrow assessment (BMA) ≤6 weeks prior to treatment
* Either chronic-phase CML, with \<15% blasts in peripheral blood and bone marrow, or advanced-phase CML, including Ph+ acute lymphoblastic leukemia (ALL) (\> 5% blasts) or hematologic progression with ≥15% blasts not in complete cytogenetic remission
* Resistance or suboptimal response to imatinib, dasatinib, or nilotinib and no known T315I/A Abl-kinase mutation.

Exclusion Criteria

* Known Abl-kinase T315I or T315A mutation
* CCyR at baseline
* Any serious or uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy
* Uncontrolled or significant cardiovascular disease
* Grade 3 or higher peripheral blood counts
* Serum calcium or phosphate below the lower limit of normal
* Baseline hypomagnesemia and amylase or lipase at least Grade 1 or higher
* Reduced renal function, defined as serum creatinine level \>3\*upper limit of normal
* Prior therapies for CML or Ph+ ALL permitted, with the following restriction:

* Therapy permitted with corticosteroids, hydroxyurea, or anagrelide prior to starting treatment and during the first 4 weeks on study
* 6 months or longer after stem cell transplantation
* 28 days or longer after any investigational agent
* 7 days or longer after any standard chemotherapy agent
* Concomitant use of medications with a known risk of causing Torsades de Pointes
* Concomitant use of strong inhibitors of the CYP3A4 isoenzyme
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

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University Of California Medical Center

San Francisco, California, United States

Site Status

Sidney Kimmel Cancer Center At Johns Hopkins

Baltimore, Maryland, United States

Site Status

Ut M.D. Anderson Cancer Center

Houston, Texas, United States

Site Status

Local Institution

Hamilton, Ontario, Canada

Site Status

Local Institution

Toronto, Ontario, Canada

Site Status

Local Institution

Helsinki, , Finland

Site Status

Local Institution

Bordeaux, , France

Site Status

Local Institution

Poitiers, , France

Site Status

Local Institution

Frankfurt am Main, , Germany

Site Status

Local Institution

Bologna, , Italy

Site Status

Local Institution

Orbassano(To), , Italy

Site Status

Local Institution

Glasgow, , United Kingdom

Site Status

Countries

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United States Canada Finland France Germany Italy United Kingdom

Related Links

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Other Identifiers

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2010-019480-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CA180-323

Identifier Type: -

Identifier Source: org_study_id

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