Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 24 of 128 for:    Venetoclax AND complete response

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01994837
Recruitment Status : Completed
First Posted : November 26, 2013
Results First Posted : January 23, 2018
Last Update Posted : June 5, 2018
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
AbbVie

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).

Condition or disease Intervention/treatment Phase
Acute Myelogenous Leukemia AML Acute Myeloid Leukemia Drug: ABT-199 Phase 2

Detailed Description:
The primary objective was to evaluate the preliminary efficacy of venetoclax administered orally in participants with relapsed and/or refractory (R/R) acute myelogenous leukemia (AML) or frontline therapy in patients with AML who were unfit for intensive therapy. The secondary objective was to evaluate the preliminary safety of venetoclax administered orally in patients with AML. The first portion of the study was to consist of 19 participants with the objective of evaluating anti-tumor effects and confirming the safety of the regimen. The second portion (expansion) was to consist of 35 additional subjects to evaluate anti-tumor effects and safety and was to commence if an adequate efficacy signal (i.e., ≥ 5/19 achieved complete remission [CR], CR with incomplete bone marrow recovery [CRi] or partial remission [PR]) had been observed in the first portion of the study. The criterion for success would have been met if ≥ 16 of 54 participants achieved remission. The efficacy signal from first portion of the study was deemed insufficient for enrollment into the second portion of the study, as 4 of the 19 subjects achieved CR/CRi. During the trial, a number of participants were in screening at the point of the interim analysis. Given the early signs of clinical activity of venetoclax, disease severity, and prognosis of these participants without available options for therapy, they were allowed to initiate treatment ahead of completion of the interim analysis. Therefore, 32 participants were enrolled. No additional participants were screened or treated after the interim analysis was completed.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of ABT-199 in Subjects With Acute Myelogenous Leukemia (AML)
Study Start Date : November 2013
Actual Primary Completion Date : December 2014
Actual Study Completion Date : December 2014


Arm Intervention/treatment
Experimental: ABT-199
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
Tablet
Other Name: ABT-199 also known as venetoclax




Primary Outcome Measures :
  1. Objective Remission Rate [ Time Frame: When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier ]
    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.


Secondary Outcome Measures :
  1. Complete Remission Rate [ Time Frame: When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier ]
    The complete remission (CR) rate was defined as the percentage of participants who achieved CR per the International Working Group criteria for AML. Complete remission was defined as peripheral neutrophils at least 10˄3/μL, platelets ≥ 10˄5/μL and normocellular bone marrow with ≤ 5% blasts.

  2. Duration of Remission [ Time Frame: 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 was defined as the number of days from the date of first remission (CR, CRi, or PR) per the International Working Group criteria for AML to the earliest recurrence or progressive disease (PD). In this study, the duration of remission analysis was not performed because of the low remission rate, per the Statistical Analysis Plan.

  3. Time to Progression [ Time Frame: 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 was defined as the number of months from the date of enrollment to the date of earliest disease progression. If a participant did not experience disease progression, then the data for that participant was censored at the date of the last disease assessment.

  4. Progression-free Survival [ Time Frame: 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 was defined as the number of months from the date of enrollment to the date of earliest progression or death. If a participant did not experience disease progression or death, then the data was censored at the date of the last disease assessment.

  5. Overall Survival [ Time Frame: Measured up to 2 years after the last subject had enrolled in the study. ]
    Overall survival was defined as the number of months from the date of enrollment to the date of death for all dosed participants. For participants who did not die, their data were censored at the date of last study visit or the last known date to be alive, whichever was later.

  6. Percentage of Participants Who Received Subsequent Stem Cell Transplant [ Time Frame: When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier ]
    The percentage of participants who received a subsequent allogenic (from a healthy donor) stem cell transplant was summarized.

  7. Rate of Minimal Residual Disease (MRD) Negativity [ Time Frame: When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier ]
    The rate of minimal residual disease (MRD) response was defined as the percentage of participants who had MRD negative status. Only participants with a reported MRD assessment (negative or positive) from the local laboratory at the investigator site were used in the calculation of MRD response rate.

  8. Complete Remission With Incomplete Marrow Recovery (CRi) Rate [ Time Frame: When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier ]
    The complete remission with incomplete bone marrow recovery (CRi) rate was defined as the percentage of participants who achieved CRi per the International Working Group criteria for AML. Complete remission with incomplete bone marrow recovery was defined as bone marrow with less than 5% blasts, with peripheral neutrophils of at least 10˄3/μL or platelets ≥ 10˄5/μL.

  9. Complete Remission Rate and Complete Remission With Incomplete Marrow Recovery (CRi) Rate [ Time Frame: When 19 participants had completed at least 12 weeks of treatment or after all enrolled participants had discontinued venetoclax, whichever was earlier ]
    The complete remission rate and the complete remission with incomplete marrow recovery rate (Cri) was defined as the percentage of participants who achieved complete remission (CR) or complete remission with incomplete bone marrow recovery (CRi), 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.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. Participant has an Eastern Cooperative Oncology Group (ECOG) Performance score of 0 to 2.
  3. 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.
  4. 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)

Exclusion Criteria:

  1. 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.
  2. Participant has received a monoclonal antibody for anti-neoplastic intent within 8 weeks prior to the first dose of study drug.
  3. 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.
  4. Participant has received CYP3A inhibitors (such as fluconazole, ketoconazole, and clarithromycin) within 5 days prior to the first dose of study drug.
  5. Participant has a white blood cell count > 25 x 10^9/L.
  6. Participant has acute promyelocytic leukemia (French-American-British Class M3 AML).
  7. Participants with known active central nervous system (CNS) disease.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01994837


Sponsors and Collaborators
AbbVie
Genentech, Inc.
Investigators
Layout table for investigator information
Study Director: Jalaja Potluri, MD AbbVie

Publications of Results:
Layout table for additonal information
Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT01994837     History of Changes
Other Study ID Numbers: M14-212
First Posted: November 26, 2013    Key Record Dates
Results First Posted: January 23, 2018
Last Update Posted: June 5, 2018
Last Verified: January 2018
Keywords provided by AbbVie:
GDC-0199
Acute Myelogenous Leukemia
AML
ABT-199
Acute Myeloid Leukemia
Myeloid Leukemia
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Venetoclax
Antineoplastic Agents