- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01110473
ABT-348 as Monotherapy and in Combination With Azacitidine to Treat Advanced Hematologic Malignancies
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
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Arizona
-
Scottsdale, Arizona, United States, 85259
- Site Reference ID/Investigator# 59324
-
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Georgia
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Atlanta, Georgia, United States, 30322
- Site Reference ID/Investigator# 26523
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Texas
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Houston, Texas, United States, 77030-4009
- Site Reference ID/Investigator# 26522
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
- Serum creatinine value of ≤ 1.8 times the upper limit of normal (ULN) and either an estimated creatinine clearance value as determined by the Cockcroft-Gault formula or based on a 24 hour urine collection creatinine clearance value of ≥ 50 mL/min
- Adequate liver function as demonstrated by serum bilirubin < 2 x ULN and AST and ALT < 2.5 x ULN
- QTc interval < 500 msec
- Left Ventricular Ejection Fraction > 50%
- Women of child-bearing potential and men must agree to use adequate contraception prior to the study entry, for the duration of study participation and up to 3 months following completion of therapy.
- Capable of understanding and complying with parameters as outlined in the protocol and able to sign informed consent, approved by an Institutional Review Board (IRB) prior to the initiation of any screening or study-specific procedures.
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 1. Per Investigator discretion, hydroxyurea may be used anytime during the study. Tyrosine kinase inhibitors may not be administered 7 days prior to Study Day 1.
- 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
- Subject is receiving therapeutic anticoagulation therapy. Low-dose anticoagulation (e.g., low-dose heparin or warfarin) for catheter prophylaxis will be allowed
- Subject has infection with HIV, Hepatitis B, or Hepatitis C
- Female subjects who are pregnant or breast feeding
- Any medical condition which in the opinion of the study investigator places the subject at an unacceptably high risk for toxicities
- Clinically significant uncontrolled condition(s)
- Subjects in Arm C who have advanced malignant hepatic tumors
- Subjects in Arm C who have hypersensitivity to azacitidine or mannitol
- Subjects have received CYP3A inhibitors or inducers within 7 days prior to the first dose of study drug.
- Subjects enrolled in Arm D who have hypersensitivity to drugs formulated with polyethoxylated castor oil (Cremophor).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Monotherapy, once daily
|
An oral dose of ABT-348, once daily on Day 1, Day 8, and Day 15 of each 28 day cycle.
An oral dose of ABT-348, twice daily on Day 1, Day 8, and Day 15 of each 28 day cycle
An intravenous dose of ABT-348, once daily on Day 1, Day 8, and Day 15 of each 28 day cycle.
|
Experimental: Monotherapy, twice daily
|
An oral dose of ABT-348, once daily on Day 1, Day 8, and Day 15 of each 28 day cycle.
An oral dose of ABT-348, twice daily on Day 1, Day 8, and Day 15 of each 28 day cycle
An intravenous dose of ABT-348, once daily on Day 1, Day 8, and Day 15 of each 28 day cycle.
|
Experimental: Combination with Azacitidine
|
An oral dose of ABT-348, once daily on Day 1, Day 8, and Day 15 of each 28 day cycle.
An oral dose of ABT-348, twice daily on Day 1, Day 8, and Day 15 of each 28 day cycle
An intravenous dose of ABT-348, once daily on Day 1, Day 8, and Day 15 of each 28 day cycle.
An oral dose of ABT-348 on Day 1, Day 8, and Day 15 of each 28 day cycle.
An IV or injection of azacitidine on Days 1-7 of each 28 day cycle.
|
Experimental: IV monotherapy, once daily
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An oral dose of ABT-348, once daily on Day 1, Day 8, and Day 15 of each 28 day cycle.
An oral dose of ABT-348, twice daily on Day 1, Day 8, and Day 15 of each 28 day cycle
An intravenous dose of ABT-348, once daily on Day 1, Day 8, and Day 15 of each 28 day cycle.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
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
|
At study visits
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
Time Frame: At each treatment visit
|
At each treatment visit
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Neoplasms by Site
- Bone Marrow Diseases
- Hematologic Diseases
- Myeloproliferative Disorders
- Leukemia, Lymphoid
- Leukemia, B-Cell
- Hematologic Neoplasms
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Azacitidine
- Ilorasertib
Other Study ID Numbers
- M10-943
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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