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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:
NCT01399840
First received: July 13, 2011
Last updated: May 21, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
Acute Myeloid Leukemia
Myelodysplastic Syndrome
Chronic Lymphocytic Leukemia
Mantle Cell Lymphoma
Drug: BMN 673
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by BioMarin Pharmaceutical:

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). [ Time Frame: Assessed after each visit until completion (Estimated duration is 12-18 months) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of participants with adverse events [ Time Frame: Assessed after each visit until completion of the study (Estimated duration is 24-30 months) ] [ Designated as safety issue: Yes ]
  • Determine the pharmacokinetic (PK) profile of BMN 673 [ Time Frame: Assessed at each visit in cycle 1 - 5 (Estimated duration is 24 months) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Assessed after each visit until completion of the study (Estimated duration is 24-30 months) ] [ Designated as safety issue: No ]
  • Assess preliminary efficacy of BMN 673 by evaluating per response publications [ Time Frame: Assessed approximately every 4-12 weeks (Estimated duration is 24-30 months) ] [ Designated as safety issue: No ]

Enrollment: 33
Study Start Date: June 2011
Study Completion Date: May 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 exclusion criteria:

    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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01399840

Locations
United States, Indiana
Indiana University Simon Cancer Center
Indianapolis, Indiana, United States, 46202
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109-1023
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53715
United Kingdom
King's College Hospital
London, United Kingdom, SE5 9RS
University College London
London, United Kingdom, NW1 2BU
The Christie NHS Foundation
Manchester, United Kingdom, M20 4BX
University of Newcastle Upon Tyne, NHS Foundation Trust
Newcastle upon Tyne, United Kingdom, NE1 7RU
Sponsors and Collaborators
BioMarin Pharmaceutical
Investigators
Study Director: Andrew Dorr, MD BioMarin Pharmaceutical
  More Information

No publications provided

Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT01399840     History of Changes
Other Study ID Numbers: PRP-002
Study First Received: July 13, 2011
Last Updated: May 21, 2014
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Lymphoma
Myelodysplastic Syndromes
Preleukemia
Lymphoma, Mantle-Cell
Hematologic Neoplasms
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Lymphoma, Non-Hodgkin
Neoplasms by Site

ClinicalTrials.gov processed this record on July 24, 2014