NCT01110473

Completed

Phase 1

A Phase 1 Study Evaluating the Safety and Pharmacokinetics of ABT-348 as Monotherapy and in Combination With Azacitidine in Subjects With Advanced Hematologic Malignancies

AbbVie (prior sponsor, Abbott)3 sites in 1 country52 target enrollmentApril 2010

ConditionsAcute Lymphoblastic Leukemia Acute Myelogenous Leukemia B-cell Chronic Lymphocytic Leukemia Chronic Myelogenous Leukemia Myelodysplasia

InterventionsABT-348 ABT-348 and azacitidine

DrugsABT-348 ABT-348 and azacitidine

Overview

Phase: Phase 1
Intervention: ABT-348
Conditions: Acute Lymphoblastic Leukemia
Sponsor: AbbVie (prior sponsor, Abbott)
Enrollment: 52
Locations: 3
Primary Endpoint: Determine the safety profile (adverse events by toxicity grade and relationship to study drug, serious adverse events, adverse events leading to discontinuation and relevant clinical laboratory abnormalities) of ABT-348 as monotherapy or in combination
Status: Completed
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to determine the safety, pharmacokinetics and maximum tolerated dose of ABT-348 as monotherapy and when given in combination with azacitidine.

Detailed Description

The primary objectives of this study are to determine safety and pharmacokinetics of ABT-348 as monotherapy and when given in combination with azacitidine. The secondary objectives are to determine the maximum tolerated dose and recommended Phase 2 dose of ABT-348 when administered as monotherapy and when given in combination with azacitidine in subjects with advanced hematologic malignancies.

Registry

clinicaltrials.gov

Start Date

April 2010

End Date

June 2013

Last Updated

8 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

AbbVie (prior sponsor, Abbott)

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Histological or cytological confirmation of one of the following (Arms A, B and D):
•Relapsed or refractory acute myelogenous leukemia (AML), untreated AML in subjects who are \> 60 years of age and do not have favorable cytogenetics (i.e., lack t(8,21) or inv(16)/t(16,16) or acute lymphoblastic leukemia (ALL) in subjects who have failed or are unsuitable for standard therapy.
•Chronic myelogenous leukemia (CML) subjects that have not responded or relapsed on imatinib and failed second line Tyrosine Kinase Inhibitor (TKI) therapy and are not a candidate for allogeneic bone marrow transplant.
•B-cell chronic lymphocytic leukemia (CLL) subjects that have not responded or relapsed on fludarabine or in the opinion of the Principal Investigator are unsuitable for fludarabine therapy and have not responded to or relapsed on alkylating therapy.
•Myelodysplasia (MDS) including chronic myelomonocytic leukemia (CMML) subjects with International Prognostic Scoring System (IPSS) risk categories of Intermediate-2 (INT-2) or High risk, or any myelodysplasia with symptomatic anemia resistant to erythropoietin, immunosuppressant, or DNA methyltransferase inhibitor therapy (e.g., azacitidine/decitabine).
•1a. Histological or cytological confirmation of one of the following (Arm C):
•Relapsed or refractory AML, untreated AML in subjects who are \> 60 years of age and do not have favorable cytogenetics (i.e., lack t(8,21).
•Untreated MDS including CMML with IPSS risk categories of INT-2 or High risk or with more than 10% blasts in the bone marrow, or any myelodysplasia with symptomatic anemia resistant to erythropoietin, or immunosuppressant, or subject has no response after four cycles of DNA methyltransferase inhibitor therapy or subject has progressed on DNA methyltransferase inhibitor therapy.
•Eastern Cooperative Oncology Group Status of 0-2
•Hematologic function for subjects with CLL and CML demonstrated by hemoglobin \> 9 g/dL, platelets \> 100,000/µL, ANC \> 1500/mm3

Exclusion Criteria

•Subject has known active CNS involvement. The subject has untreated brain or meningeal metastases.
•ALL or AML subject has received acute anti-cancer therapy within 14 days prior to Study Day 1
•CML, CLL or myelodysplasia (MDS) subjects has received acute anti-cancer therapy within 28 days or biologic therapy within 6 weeks prior to Study Day
•Per Investigator discretion, hydroxyurea may be used anytime during the study. Tyrosine kinase inhibitors may not be administered 7 days prior to Study Day
•Subjects with poorly controlled diabetes mellitus
•Subject has unresolved toxicities from prior anti-cancer therapy, grade 2 or higher clinically significant toxicity (excluding alopecia)
•Subject has had major surgery within 28 days prior to Study Day 1
•Subject currently exhibits symptomatic or persistent, uncontrolled hypertension defined as diastolic blood pressure \> 90 mmHg or systolic blood pressure \> 140 mmHg
•Subject has proteinuria grade \> 1
•Subject is unable to swallow or absorb oral tablets normally

Arms & Interventions

Monotherapy, once daily

Intervention: ABT-348

Monotherapy, twice daily

Intervention: ABT-348

Combination with Azacitidine

Intervention: ABT-348

Combination with Azacitidine

Intervention: ABT-348 and azacitidine

IV monotherapy, once daily

Intervention: ABT-348

Outcomes

Primary Outcomes

Determine the safety profile (adverse events by toxicity grade and relationship to study drug, serious adverse events, adverse events leading to discontinuation and relevant clinical laboratory abnormalities) of ABT-348 as monotherapy or in combination

Time Frame: At each treatment visit

Study the pharmacokinetic interaction (plasma concentrations and pharmacokinetic parameter values) of ABT-348 as monotherapy and in combination

Time Frame: At study visits

Secondary Outcomes

Determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RPTD) of ABT-348 when administered as a monotherapy and in combination in subjects with advanced hematologic malignancies(At each treatment visit)