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

NCT01110473 | Completed Phase 1

• 1 other identifier: M10-943
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 3

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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

  At each treatment visit

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

  At study visits

Secondary Outcomes (1)

• 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

Study Arms (4)

Monotherapy, once daily

EXPERIMENTAL

Drug: ABT-348

Monotherapy, twice daily

EXPERIMENTAL

Drug: ABT-348

Combination with Azacitidine

EXPERIMENTAL

Drug: ABT-348; Drug: ABT-348 and azacitidine

IV monotherapy, once daily

EXPERIMENTAL

Drug: ABT-348

Interventions

ABT-348 DRUG

An oral dose of ABT-348, once daily on Day 1, Day 8, and Day 15 of each 28 day cycle.

Combination with Azacitidine; Monotherapy, once daily

ABT-348 and azacitidine DRUG

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.

Combination with Azacitidine

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• a. 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead

Study Sites (3)

Site Reference ID/Investigator# 59324

Scottsdale, Arizona, 85259, United States

Location

Site Reference ID/Investigator# 26523

Atlanta, Georgia, 30322, United States

Location

Site Reference ID/Investigator# 26522

Houston, Texas, 77030-4009, United States

Location

Related Publications (1)

• Garcia-Manero G, Tibes R, Kadia T, Kantarjian H, Arellano M, Knight EA, Xiong H, Qin Q, Munasinghe W, Roberts-Rapp L, Ansell P, Albert DH, Oliver B, McKee MD, Ricker JL, Khoury HJ. Phase 1 dose escalation trial of ilorasertib, a dual Aurora/VEGF receptor kinase inhibitor, in patients with hematologic malignancies. Invest New Drugs. 2015 Aug;33(4):870-80. doi: 10.1007/s10637-015-0242-6. Epub 2015 May 2.

  PMID: 25933833 RESULT

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Anemia, Refractory, with Excess of Blasts

Interventions

ilorasertib; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myeloproliferative Disorders; Bone Marrow Diseases; Anemia, Refractory; Anemia; Myelodysplastic Syndromes

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Gary Gordon, MD

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2010
• First Posted: April 26, 2010
• Study Start: April 1, 2010
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: November 20, 2017

Record last verified: 2013-11

Locations

US (3)