A Randomized Two-Arm, Multicenter, Open-Label Phase II Study of BMS-354825 Administered Orally at a Dose of 70 mg Twice Daily or 140 mg Once Daily in Subjects with Chronic Myeloid Leukemia in Accelerated Phase or in Myeloid or Lymphoid Blast Phase or with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia who are Resistant or Intolerant to Imatinib Mesylate (Gleevec)
- Conditions
- Subjects with Chronic Myeloid Leukemia (CML) in Accelerated Phase (AP) or in Myeloid (My) or Lymphoid (Ly) Blast Phase (BP) or with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL) who are Resistant or Intolerant to Imatinib Mesylate (Gleevec)
- Registration Number
- EUCTR2005-001169-32-ES
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not Recruiting
- Sex
- All
- Target Recruitment
- 264
1/ AP CML
Subjects with Ph+ (or BCR/ABL+) AP CML whose disease has primary or acquired hematologic resistance to imatinib mesylate or who are intolerant to imatinib mesylate.
Subjects are considered to have AP CML if they meet at least one of the following criteria:
• At least 15% to < 30% blasts in PB or in BM
• A sum of the percent of blasts and promyelocytes in PB or the BM = 30% (with < 30% blasts alone)
• = 20% basophils in PB or BM
•Platelets < 100,000/mm³ unrelated to prior drug therapy
Subjects may not have extra-medullar infiltrates of leukemic cells other than in spleen or liver.
In addition, the following subjects will be considered to be part of the AP CML population even if they do not reach the above defined values of blast % in PB or BM for accelerated phase:
• Subjects with clonal evolution (e.g. +8, +19, +Ph, iso17)
• Subjects with prior episode of AP who achieved a hematologic response and subsequently progressed
2/ BP CML
Subjects with Ph+ (or BCR/ABL+) MyBP or LyBP CML whose disease has primary or acquired hematologic resistance to imatinib mesylate or who are intolerant to imatinib mesylate.
Subjects are considered to have myeloid or lymphoid BP CML if they meet at least one of the following criteria:
• = 30% myeloid or lymphoid blasts in PB or in BM
• Extra-medullar infiltrates of leukemic cells, other than in spleen or liver, with myeloid or lymphoid blast morphology
Subjects with prior episode of BP who achieved a hematologic response and subsequently progressed but do not meet the criteria for BP CML as described above will be considered to be part of the BP CML population.
3/ Ph+ ALL
Subjects with Ph+ (or BCR/ABL+) ALL whose disease has primary or acquired hematologic resistance to imatinib mesylate or who are intolerant to imatinib mesylate.
Subjects must have received at least one prior standard induction +/- consolidation chemotherapy regimen and not be eligible for immediate autologous or allogeneic stem cell transplantation.
Subjects with CNS involvement must have received intra-thecal chemotherapy and obtain normal CSF for at least 2 weeks prior to entry. Maintenance intra-thecal chemotherapy must be given during treatment with BMS-354825.
Subjects characterisctics:
4) ECOG performance status (PS) score 0 - 2 (See Protocol Appendix 1)
5) Adequate hepatic function defined as:
• total bilirubin = 2.0 times the institutional ULN
• alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 times the institutional ULN
6) Adequate renal function defined as:
• serum creatinine = 1.5 times the institutional ULN
7) Serum Na, K, Mg, P and total serum Ca or ionized Ca levels must be greater than or equal to the institutional lower limit of normal. Subjects with low K, Mg levels, total serum Ca and/or ionized Ca must be repleted to allow for protocol entry.
8) Men and women, ages 18 and older.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1. Women who are pregnant or breastfeeding
2. WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period of at least one month before and for at least 3 months after completion of the study medication.
3. Women with a positive pregnancy test on enrollment or prior to study drug administration.
4. Subjects eligible for immediate autologous or allogeneic stem cell transplantation.
5. Subjects with active CNS involvement (presence of leukemic cells in the CSF)
6. A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy
7. Uncontrolled or significant cardiovascular disease (see Protocol section 5.2 for details)
8. Dementia or altered mental status that would prohibit the understanding or rendering of informed consent
9. History of significant bleeding disorder unrelated to CML (see Protocol section 5.2 for details)
10. Concurrent incurable malignancy other than CML
11. Evidence of organ dysfunction or digestive dysfunction that would prevent administration of study therapy
12. Subjects who received any of the following:
• imatinib mesylate within 7 days
• interferon or cytarabine within 7 days
• a targeted small molecule anti-cancer agent within 7 days including BMS-354825
• any other investigational or any antineoplastic agent other than hydroxyurea (HU) within 2 days
13. Subjects currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointe (see Protocol section 5.2 for details)
14. Subjects taking medications that irreversibly inhibit platelet function or anticoagulants
15. Prior therapy with BMS-354825
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method