A Phase 2 Study of ABT-199 in Subjects With Acute Myelogenous Leukemia (AML)

NCT01994837 | Completed Phase 2 Results

• 1 other identifier: M14-212
• Study Type: interventional
• Target: 32
• Locations: 0 countries
• Sites: N/A

Brief Summary

This was a Phase 2, open-label, multicenter study evaluating the preliminary efficacy and safety of venetoclax (ABT-199) administered orally in participants with acute myelogenous leukemia (AML).

Conditions

Acute Myelogenous Leukemia; AML; Acute Myeloid Leukemia

Keywords

GDC-0199; Acute Myelogenous Leukemia; AML; ABT-199; Acute Myeloid Leukemia; Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Objective Remission Rate

  The objective remission rate (ORR) was defined as the percentage of participants who achieved complete remission (CR), complete remission with incomplete bone marrow recovery (CRi), or partial remission (PR) per the International Working Group criteria for AML. Complete remission (CR) was defined as peripheral neutrophils at least 10˄3/μL, platelets ≥ 10˄5/μL and normocellular bone marrow with ≤ 5% blasts. Complete remission with incomplete bone marrow recovery (CRi) was defined as bone marrow with less than 5% blasts, with peripheral neutrophils of at least 10˄3/μL or platelets ≥ 10˄5/μL. Partial remission (PR) was defined as normalization in peripheral blood neutrophil and platelet counts with at least a 50% decrease in blasts persisting in bone marrow versus baseline.

  When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier

Secondary Outcomes (9)

• Complete Remission Rate

  When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier

• Duration of Remission

  When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier

• Time to Progression

  When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier

• Progression-free Survival

  When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier

• Overall Survival

  Measured up to 2 years after the last subject had enrolled in the study.

Study Arms (1)

ABT-199

EXPERIMENTAL

Continuous dosing of venetoclax (ABT-199) QD (once daily) beginning with dose-escalation on Week 1 Day 1. Participants received a dose of 20 mg of ABT-199 on Week 1 Day 1, 50 mg on Day 2, 100 mg on Day 3, 200 mg on Day 4, 400 mg on Day 5, 800 mg on Day 6 and QD thereafter.

Drug: ABT-199

Interventions

ABT-199 DRUG

Tablet

Also known as: ABT-199 also known as venetoclax

ABT-199

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 relapsed or refractory acute myelogenous leukemia (AML) (by World Health Organization \[WHO\] classification) or untreated AML in participants who are unfit for intensive therapy.
• Participant has an Eastern Cooperative Oncology Group (ECOG) Performance score of 0 to 2.
• Participant must have adequate renal function as demonstrated by a calculated creatinine clearance ≥ 50 mL/min; determined via urine collection for 24-hour creatinine clearance or by the Cockcroft Gault formula using ideal body mass (IBM) instead of mass.
• Participant must have adequate liver function as demonstrated by:
• aspartate aminotransferase (AST) ≤ 3.0 × upper limit of normal (ULN)\*
• alanine aminotransferase (ALT) ≤ 3.0 × ULN\*
• bilirubin ≤ 1.5 × ULN\* \*unless considered due to leukemic organ involvement. (Participants with Gilbert's Syndrome may have had a bilirubin \> 1.5 × ULN per discussion between the investigator and AbbVie medical monitor)

You may not qualify if:

• Participant has received acute anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal or any investigational therapy within 14 days or 5 half-lives (whichever is shorter) prior to first dose of ABT-199.
• Participant has received a monoclonal antibody for anti-neoplastic intent within 8 weeks prior to the first dose of study drug.
• Participant has received potent Cytochrome P450, family 3, subfamily A (CYP3A) inducers (such as rifampin, carbamazepine, phenytoin and St. John's wort) and warfarin or requires the use of warfarin (due to potential drug-drug interactions that may potentially increase the exposure of warfarin and complications of this effect) within 7 days prior to the first dose of study drug.
• Participant has received CYP3A inhibitors (such as fluconazole, ketoconazole, and clarithromycin) within 5 days prior to the first dose of study drug.
• Participant has a white blood cell count \> 25 x 10\^9/L.
• Participant has acute promyelocytic leukemia (French-American-British Class M3 AML).
• Participants with known active central nervous system (CNS) disease.

Sponsors & Collaborators

• AbbVie: lead
• Genentech, Inc.: collaborator

Related Publications (1)

• Konopleva M, Pollyea DA, Potluri J, Chyla B, Hogdal L, Busman T, McKeegan E, Salem AH, Zhu M, Ricker JL, Blum W, DiNardo CD, Kadia T, Dunbar M, Kirby R, Falotico N, Leverson J, Humerickhouse R, Mabry M, Stone R, Kantarjian H, Letai A. Efficacy and Biological Correlates of Response in a Phase II Study of Venetoclax Monotherapy in Patients with Acute Myelogenous Leukemia. Cancer Discov. 2016 Oct;6(10):1106-1117. doi: 10.1158/2159-8290.CD-16-0313. Epub 2016 Aug 12.

  PMID: 27520294 RESULT

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myeloid

Interventions

venetoclax

Condition Hierarchy (Ancestors)

Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

800-633-9110

Study Officials

• Jalaja Potluri, MD

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2013
• First Posted: November 26, 2013
• Study Start: November 1, 2013
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: June 6, 2018
• Results First Posted: January 23, 2018

Record last verified: 2018-01