Study of BMN 673, a PARP Inhibitor, in Patients With Advanced Hematological Malignancies

Sponsor

Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT01399840

Collaborator

Medivation, Inc. (Industry)

Enrollment

Locations

Arms

Actual Duration (Months)

4.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Myelodysplastic Syndrome Chronic Lymphocytic Leukemia Mantle Cell Lymphoma	Drug: BMN 673	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

33 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase 1, Two-arm, Open-label Study Of Once Daily, Oral Bmn 673 In Patients With Advanced Hematological Malignancies

Actual Study Start Date :

Jun 30, 2011

Actual Primary Completion Date :

Mar 31, 2014

Actual Study Completion Date :

May 31, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1: BMN 673 Arm 1 will enroll patients with either AML or MDS	Drug: BMN 673 Oral capsule with multiple dosage forms given once daily
Experimental: Arm 2: BMN 673 Arm 2 will enroll patients with either CLL or MCL	Drug: BMN 673 Oral capsule with multiple dosage forms given once daily

Arm

Intervention/Treatment

Experimental: Arm 1: BMN 673

Arm 1 will enroll patients with either AML or MDS

Drug: BMN 673

Oral capsule with multiple dosage forms given once daily

Experimental: Arm 2: BMN 673

Arm 2 will enroll patients with either CLL or MCL

Drug: BMN 673

Oral capsule with multiple dosage forms given once daily

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

18 years of age or older.
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
Arm 1 AML/MDS: Must have available tissue
Arm 2 CLL/MCL: Must have available tissue
Have adequate organ function as defined below:
Serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 X upper limit of normal (ULN);
Total serum bilirubin ≤ 1.5 X ULN;
Able to take oral medications
Recovered from acute toxicity of prior treatment
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.
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.
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.
Willing and able to comply with all study procedures.

Exclusion Criteria:

Acute promyelocytic leukemia, APL [AML with t(15;17)(q22;q12), PML-RARA and variants].
Disease-specific exclusion criteria:

AML: i. Marrow cellularity < 25% ii. Circulating blasts > 50,000/mm3 b. MCL and CLL: i. Platelet count < 50,000/mm3 ii. Neutrophil count < 1000/mm3

Autologous bone marrow transplant < 6 months before Cycle 1 Day 1
Prior allogeneic bone marrow transplant < 6 months before Cycle 1 Day 1 and/or with the presence of graft versus host disease (GVHD)
Prior treatment:
AML: anti-leukemia treatment within 14 days before Cycle 1 Day 1; hydroxyurea treatment within 7 days before Cycle 1 Day 1.
CLL, MCL or MDS: anti-lymphoma/leukemia treatment within 28 days before Cycle 1 Day 1;
CLL/MCL patients who have received transfusion, hematopoietic growth factors within 7 days before Cycle 1 Day 1.
Symptomatic central nervous system (CNS) involvement.
Known to have human immunodeficiency virus (HIV) or active hepatitis C virus (HCV) or hepatitis B virus (HBV).
Major surgery within 28 days before Cycle 1, Day 1.
Active peptic ulcer disease.
Active gastrointestinal tract disease with malabsorption syndrome.
Requirement for IV alimentation.
Prior surgical procedures affecting absorption.
Uncontrolled inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
Myocardial infarction within 6 months before Cycle 1 Day 1, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication.
Breastfeeding at screening or planning to become pregnant (self or partner) at any time during study participation.
Use of any investigational product or investigational medical device within 28 days before Cycle 1, Day 1.
Concurrent disease or condition that would interfere with study participation or safety, such as:
CLL/MCL patients with active, clinically significant infection requiring the use of parenteral anti-microbial agents, or grade > 2 infection by NCI CTCAE (v4.03) within 14 days before Cycle 1, Day 1(AML/MDS patients with controlled infection are eligible for the study with no specific time requirement prior to Cycle 1, Day 1);
Clinically significant bleeding diathesis or coagulopathy, including known platelet function disorders;
Non-healing wound, ulcer, or bone fracture.
Patients who have received prior treatment with a PARP inhibitor are not eligible for Part 2 of the study (expansion), but are eligible for Part 1 (dose escalation) of the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Indiana University Simon Cancer Center	Indianapolis	Indiana	United States	46202
2	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109-1023
3	University of Wisconsin	Madison	Wisconsin	United States	53715
4	University College London	London		United Kingdom	NW1 2BU
5	King's College Hospital	London		United Kingdom	SE5 9RS
6	The Christie NHS Foundation	Manchester		United Kingdom	M20 4BX
7	University of Newcastle Upon Tyne, NHS Foundation Trust	Newcastle upon Tyne		United Kingdom	NE1 7RU