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

NCT ID: NCT01399840

Last Updated: 2017-09-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

33 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-06-30

Study Completion Date

2014-05-31

Brief Summary

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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.

Detailed Description

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Conditions

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Acute Myeloid Leukemia Myelodysplastic Syndrome Chronic Lymphocytic Leukemia Mantle Cell Lymphoma

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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Arm 1: BMN 673

Arm 1 will enroll patients with either AML or MDS

Group Type EXPERIMENTAL

BMN 673

Intervention Type DRUG

Oral capsule with multiple dosage forms given once daily

Arm 2: BMN 673

Arm 2 will enroll patients with either CLL or MCL

Group Type EXPERIMENTAL

BMN 673

Intervention Type DRUG

Oral capsule with multiple dosage forms given once daily

Interventions

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BMN 673

Oral capsule with multiple dosage forms given once daily

Intervention Type DRUG

Eligibility Criteria

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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 \[AML with t(15;17)(q22;q12), PML-RARA and variants\].

a. 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
3. Autologous bone marrow transplant \< 6 months before Cycle 1 Day 1
4. Prior allogeneic bone marrow transplant \< 6 months before Cycle 1 Day 1 and/or with the presence of graft versus host disease (GVHD)
5. Prior treatment:

1. AML: anti-leukemia treatment within 14 days before Cycle 1 Day 1; hydroxyurea treatment within 7 days before Cycle 1 Day 1.
2. CLL, MCL or MDS: anti-lymphoma/leukemia treatment within 28 days before Cycle 1 Day 1;
6. CLL/MCL patients who have received transfusion, hematopoietic growth factors within 7 days before Cycle 1 Day 1.
7. Symptomatic central nervous system (CNS) involvement.
8. Known to have human immunodeficiency virus (HIV) or active hepatitis C virus (HCV) or hepatitis B virus (HBV).
9. Major surgery within 28 days before Cycle 1, Day 1.
10. Active peptic ulcer disease.
11. Active gastrointestinal tract disease with malabsorption syndrome.
12. Requirement for IV alimentation.
13. Prior surgical procedures affecting absorption.
14. Uncontrolled inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
15. 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.
16. Breastfeeding at screening or planning to become pregnant (self or partner) at any time during study participation.
17. Use of any investigational product or investigational medical device within 28 days before Cycle 1, Day 1.
18. Concurrent disease or condition that would interfere with study participation or safety, such as:

1. 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);
2. Clinically significant bleeding diathesis or coagulopathy, including known platelet function disorders;
3. Non-healing wound, ulcer, or bone fracture.
19. 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Medivation, Inc.

INDUSTRY

Sponsor Role collaborator

Pfizer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

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Indiana University Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

University of Wisconsin

Madison, Wisconsin, United States

Site Status

University College London

London, , United Kingdom

Site Status

King's College Hospital

London, , United Kingdom

Site Status

The Christie NHS Foundation

Manchester, , United Kingdom

Site Status

University of Newcastle Upon Tyne, NHS Foundation Trust

Newcastle upon Tyne, , United Kingdom

Site Status

Countries

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United States United Kingdom

References

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Gopal AK, Popat R, Mattison RJ, Menne T, Bloor A, Gaymes T, Khwaja A, Juckett M, Chen Y, Cotter MJ, Mufti GJ. A Phase I trial of talazoparib in patients with advanced hematologic malignancies. Int J Hematol Oncol. 2021 Oct 22;10(3):IJH35. doi: 10.2217/ijh-2021-0004. eCollection 2021 Sep.

Reference Type DERIVED
PMID: 34840720 (View on PubMed)

Other Identifiers

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2010-023964-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

C3441022

Identifier Type: OTHER

Identifier Source: secondary_id

PRP-002

Identifier Type: -

Identifier Source: org_study_id