ABT-348 as Monotherapy and in Combination With Azacitidine to Treat Advanced Hematologic Malignancies

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01110473
First received: March 26, 2010
Last updated: November 19, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Acute Lymphoblastic Leukemia
Acute Myelogenous Leukemia
B-cell Chronic Lymphocytic Leukemia
Chronic Myelogenous Leukemia
Myelodysplasia
Drug: ABT-348
Drug: ABT-348 and azacitidine
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: 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

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • Study the pharmacokinetic interaction (plasma concentrations and pharmacokinetic parameter values) of ABT-348 as monotherapy and in combination [ Time Frame: At study visits ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 52
Study Start Date: April 2010
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Monotherapy, once daily Drug: ABT-348
An oral dose of ABT-348, once daily on Day 1, Day 8, and Day 15 of each 28 day cycle.
Experimental: Monotherapy, twice daily Drug: ABT-348
An oral dose of ABT-348, twice daily on Day 1, Day 8, and Day 15 of each 28 day cycle
Experimental: Combination with Azacitidine Drug: ABT-348
An oral dose of ABT-348, once daily on Day 1, Day 8, and Day 15 of each 28 day cycle.
Drug: ABT-348 and azacitidine
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 Drug: ABT-348
An intravenous dose of ABT-348, once daily on Day 1, Day 8, and Day 15 of each 28 day cycle.

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.

  Eligibility

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

Inclusion Criteria:

  1. 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.
  2. Eastern Cooperative Oncology Group Status of 0-2
  3. Hematologic function for subjects with CLL and CML demonstrated by hemoglobin > 9 g/dL, platelets > 100,000/µL, ANC > 1500/mm3
  4. 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
  5. Adequate liver function as demonstrated by serum bilirubin < 2 x ULN and AST and ALT < 2.5 x ULN
  6. QTc interval < 500 msec
  7. Left Ventricular Ejection Fraction > 50%
  8. 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.
  9. 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:

  1. Subject has known active CNS involvement. The subject has untreated brain or meningeal metastases.
  2. ALL or AML subject has received acute anti-cancer therapy within 14 days prior to Study Day 1
  3. 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.
  4. Subjects with poorly controlled diabetes mellitus
  5. Subject has unresolved toxicities from prior anti-cancer therapy, grade 2 or higher clinically significant toxicity (excluding alopecia)
  6. Subject has had major surgery within 28 days prior to Study Day 1
  7. Subject currently exhibits symptomatic or persistent, uncontrolled hypertension defined as diastolic blood pressure > 90 mmHg or systolic blood pressure > 140 mmHg
  8. Subject has proteinuria grade > 1
  9. Subject is unable to swallow or absorb oral tablets normally
  10. Subject is receiving therapeutic anticoagulation therapy. Low-dose anticoagulation (e.g., low-dose heparin or warfarin) for catheter prophylaxis will be allowed
  11. Subject has infection with HIV, Hepatitis B, or Hepatitis C
  12. Female subjects who are pregnant or breast feeding
  13. Any medical condition which in the opinion of the study investigator places the subject at an unacceptably high risk for toxicities
  14. Clinically significant uncontrolled condition(s)
  15. Subjects in Arm C who have advanced malignant hepatic tumors
  16. Subjects in Arm C who have hypersensitivity to azacitidine or mannitol
  17. Subjects have received CYP3A inhibitors or inducers within 7 days prior to the first dose of study drug.
  18. Subjects enrolled in Arm D who have hypersensitivity to drugs formulated with polyethoxylated castor oil (Cremophor).
  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: NCT01110473

Locations
United States, Arizona
Site Reference ID/Investigator# 59324
Scottsdale, Arizona, United States, 85259
United States, Georgia
Site Reference ID/Investigator# 26523
Atlanta, Georgia, United States, 30322
United States, Texas
Site Reference ID/Investigator# 26522
Houston, Texas, United States, 77030-4009
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Gary Gordon, MD AbbVie
  More Information

No publications provided

Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT01110473     History of Changes
Other Study ID Numbers: M10-943
Study First Received: March 26, 2010
Last Updated: November 19, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 01, 2014