Acute Myeloid Leukemia, Chronic Lymphocytic Leukemia, Mantle Cell Lymphoma, Myelodysplastic Syndrome
Conditions
Brief summary
This is a two-arm, open-label study to determine the maximum tolerated dose (MTD) and assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of BMN 673 in patients with Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL). Arm 1 will enroll patients with either AML or MDS; Arm 2 will enroll patients with either CLL or MCL.
Interventions
DRUGBMN 673
Oral capsule with multiple dosage forms given once daily
Sponsors
Medivation, Inc.
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 18 years of age or older. 2. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 3. Arm 1 AML/MDS: Must have available tissue 4. Arm 2 CLL/MCL: Must have available tissue 5. Have adequate organ function as defined below: 1. Serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 X upper limit of normal (ULN); 2. Total serum bilirubin ≤ 1.5 X ULN; 6. Able to take oral medications 7. Recovered from acute toxicity of prior treatment 8. Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures. 9. If sexually active, must be willing to use an acceptable method of contraception during therapy and for 30 days after the last dose of BMN 673. 10. If female of childbearing potential, must have a negative serum pregnancy test at screening and be willing to have additional pregnancy tests during the study. 11. Willing and able to comply with all study procedures.
Exclusion criteria
1. Acute promyelocytic leukemia, APL \[AML with t(15;17)(q22;q12), PML-RARA and variants\]. 2. Disease-specific
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary outcome of this study is to determine the MTD of daily oral BMN 673 in patients with AML and MDS (Arm 1) and patients with CLL and MCL (Arm 2). | Assessed after each visit until completion (Estimated duration is 12-18 months) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with adverse events | Assessed after each visit until completion of the study (Estimated duration is 24-30 months) | — |
| Determine the pharmacokinetic (PK) profile of BMN 673 | Assessed at each visit in cycle 1 - 5 (Estimated duration is 24 months) | Sample collection times vary per visit. PK parameters that will be evaluated include: maximum concentration (Cmax), minimum concentration (Cmin), time to maximum plasma concentration (Tmax), area under the curve from 0 to last quantifiable sampling point postdose (AUC0-inf), area under the curve extrapolated to infinity (AUC0-last), half life (t1/2), systemic clearance (CL/f) and volume of ditribution (VZ/f) |
| Determine the Recommended Phase 2 Dose (RP2D) of oral daily BMN 673 | Assessed after each visit until completion of the study (Estimated duration is 24-30 months) | — |
| Assess preliminary efficacy of BMN 673 by evaluating per response publications | Assessed approximately every 4-12 weeks (Estimated duration is 24-30 months) | — |
Countries
United Kingdom, United States
Outcome results
None listed