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

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01399840
• Other study ID #: PRP-002
• Secondary ID: 2010-023964-42C3
• Status: Completed
• Phase: Phase 1
• First received: July 13, 2011
• Last updated: September 14, 2017
• Start date: June 30, 2011
• Est. completion date: May 31, 2014

Study information

• Verified date: September 2017
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: May 31, 2014
• Est. primary completion date: March 31, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Leukemia, Myeloid, Acute
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Drug:
• BMN 673
Oral capsule with multiple dosage forms given once daily

Locations

Country	Name	City	State
United Kingdom	King's College Hospital	London
United Kingdom	University College London	London
United Kingdom	The Christie NHS Foundation	Manchester
United Kingdom	University of Newcastle Upon Tyne, NHS Foundation Trust	Newcastle upon Tyne
United States	Indiana University Simon Cancer Center	Indianapolis	Indiana
United States	University of Wisconsin	Madison	Wisconsin
United States	Seattle Cancer Care Alliance	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Pfizer	Medivation, Inc.

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number of participants with adverse events		Assessed after each visit until completion of the study (Estimated duration is 24-30 months)
Secondary	Determine the pharmacokinetic (PK) profile of BMN 673	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)	Assessed at each visit in cycle 1 - 5 (Estimated duration is 24 months)
Secondary	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)
Secondary	Assess preliminary efficacy of BMN 673 by evaluating per response publications		Assessed approximately every 4-12 weeks (Estimated duration is 24-30 months)