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Study of ABT-199 (GDC-0199) in Combination With Azacitidine or Decitabine (Chemo Combo) in Subjects With Acute Myelogenous Leukemia (AML)

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ClinicalTrials.gov Identifier: NCT02203773
Recruitment Status : Active, not recruiting
First Posted : July 30, 2014
Last Update Posted : December 22, 2020
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
AbbVie

Study Description
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Brief Summary:
This is a Phase 1b, open-label, non-randomized, multicenter study to evaluate the safety and pharmacokinetics of orally administered ABT-199 combined with decitabine or azacitidine and the preliminary efficacy of these combinations. In addition, there is a drug-drug interaction (DDI) sub-study only at a single site, to assess the pharmacokinetics and safety of ABT-199 in combination with posaconazole.

Condition or disease Intervention/treatment Phase
Acute Myelogenous Leukemia Myelogenous Leukemia Treatment Naive AML Drug: Posaconazole Drug: ABT-199 Drug: Decitabine Drug: Azacitidine Phase 1 Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 260 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Study of ABT-199 (GDC-0199) in Combination With Azacitidine or Decitabine in Treatment-Naive Subjects With Acute Myelogenous Leukemia Who Are Greater Than or Equal to 60 Years of Age and Who Are Not Eligible for Standard Induction Therapy
Actual Study Start Date : October 6, 2014
Estimated Primary Completion Date : September 27, 2021
Estimated Study Completion Date : September 27, 2021

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Arms and Interventions
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Arm Intervention/treatment
Experimental: ABT-199 + Azacitidine
Treatment Naive Acute Myelogenous Leukemia
 Drug: ABT-199
ABT-199 is taken orally once daily starting on Day 2 of cycle 1 and begin on day 1 of every other cycle thereafter. This is a dose escalation study, therefore the dose of ABT-199 will change.

Drug: Azacitidine
Azacitidine will be administered by IV infusion over 10 to 40 minutes or subcutaneously based on the institutional guidelines, beginning on Day 1 through Day 7 of each Cycle, for a minimum of 4 Cycles.
Experimental: ABT-199 + Decitabine
Treatment Naive Acute Myelogenous Leukemia
 Drug: ABT-199
ABT-199 is taken orally once daily starting on Day 2 of cycle 1 and begin on day 1 of every other cycle thereafter. This is a dose escalation study, therefore the dose of ABT-199 will change.

Drug: Decitabine
Decitabine will be administered by IV infusion over 1 hour beginning on Day 1 thru Day 5 of each Cycle for a minimum of 4 Cycles
Experimental: ABT-199+Decitabine+Posaconazole
Treatment Naive Acute Myelogenous Leukemia
 Drug: Posaconazole
Posaconazole will be administered orally twice a day on Cycle 1 Day 21 and once daily from Cycle 1 Day 22 to Cycle 1 Day 28.

Drug: ABT-199
ABT-199 is taken orally once daily starting on Day 2 of cycle 1 and begin on day 1 of every other cycle thereafter. This is a dose escalation study, therefore the dose of ABT-199 will change.

Drug: Decitabine
Decitabine will be administered by IV infusion over 1 hour beginning on Day 1 thru Day 5 of each Cycle for a minimum of 4 Cycles


Outcome Measures
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Primary Outcome Measures :
  1. Complete Remission Rate [ Time Frame: Measured up to 1 year after the last subject last dose ]
    Complete Remission Rate will be determined by the number of subjects who achieve a Complete Remission.

  2. The area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration (AUCt) [ Time Frame: For approximately 5 days following a single dose of ABT-199. ]
    The area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration.

  3. Complete Remission with incomplete blood count recovery rate [ Time Frame: Measured up to 1 year after the last subject last dose ]
    Complete Remission with incomplete blood count recovery Rate will be determined by the number of subjects who achieve a Complete Remission with incomplete blood count recovery.

  4. half-life (t1/2) [ Time Frame: For approximately 5 days following a single dose of ABT-199. ]
    The time required for the concentration of the drug to reach half of its original value.

  5. Maximum observed plasma concentration (Cmax) [ Time Frame: For approximately 5 days following a single dose of ABT-199. ]
    Maximum observed concentration, occurring at Tmax.

  6. Overall Response Rate [ Time Frame: Measured up to 1 year after the last subject last dose ]
    Overall response rate will be defined as the proportion of subjects who achieve a complete remission (CR), complete remission incomplete (CRi), or partial remission(PR) per the International Working Group criteria for AML.

  7. Clearance (CL) [ Time Frame: For approximately 5 days following a single dose of ABT-199. ]
    Clearance is defined as the rate at which drug is cleared from the blood.

  8. AUC from 0-24 (AUC0-24) [ Time Frame: For approximately 5 days following a single dose of ABT-199. ]
    The area under the plasma concentration-time curve (AUC) over a 24-hour dose interval.

  9. Time to Cmax (peak time, Tmax), [ Time Frame: For approximately 5 days following a single dose of ABT-199. ]
    The time at which maximum plasma concentration (Cmax) is observed.

  10. AUC from 0 to infinity (AUC∞) [ Time Frame: For approximately 5 days following a single dose of ABT-199. ]
    Area under the plasma concentration-versus-time curve from time zero to infinity.

  11. Overall Survival [ Time Frame: Measured up to 1 year after the last subject last dose ]
    Overall survival will be defined as the number of days from the date of enrollment to the date of death.


Secondary Outcome Measures :
  1. Percent of subjects who move on to stem cell transplant [ Time Frame: Measured up to 1 year after the last subject last dose ]
    The percent of subjects who move on to stem cell transplant will be summarized.

  2. Duration of Response [ Time Frame: Measured up to 1 year after the last subject last dose ]
    Duration of response will be defined as the number of days from the date of first response per the IWG criteria for AML to the earliest recurrence or progressive disease (PD).

  3. Event Free Survival [ Time Frame: Measured up to 1 year after the last subject last dose ]
    Event-free survival (EFS) will be defined as the number of days from the date of first dose to the date of earliest evidence of relapse, subsequent treatment other than stem cell transplant while in composite complete response (CR + CRi), or death.


Eligibility Criteria
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Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must have confirmation of Acute Myeloid Leukemia (AML) by WHO criteria and be ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to co-morbidity or other factors.
  • Subject must have received no prior treatment for AML with the exception of hydroxyurea
  • Subjects must have Eastern Cooperative Oncology Group (ECOG) Performance Status of ) to 2 for subjects greater than or equal to 75 years of age, or 0 to 3 for subjects greater than or equal to 60 to 74 years of age
  • Subject must have adequate kidney and liver function as described in the protocol

Exclusion Criteria:

  • Subject has received treatment with the following hypomethylating agent and/or chemo therapeutic agent for for an antecedent hematologic disorder (AHD) (Subjects may have been treated with other agents for AHD i.e., Myelodysplastic syndrome [MDS])
  • Subject has history of Myeloproliferative Neoplasm (MPN).
  • Subject has favorable risk cytogenetics as categorized by the National Comprehensive Cancer Network Guidelines Version 2, 2014 for AML.
  • Subject has t(8;21), inv(16), t(16;16) or t(15;17) karyotype abnormalities.
  • Subject has acute promyelocytic leukemia.
  • Subject has known active central nervous system involvement with AML.
  • Subject has received a strong and/or moderate CYP3A inducer within 7 days prior to the initiation of study treatment.

  • Subject has a history of other malignancies .prior to study entry, with the exception of:

    • Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;
    • Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
    • Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
  • Subject has a white blood cell count > 25 × 10^9/L. Note: Hydroxyurea is permitted to meet this criterion.
Contacts and Locations
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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): NCT02203773


Locations
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Sponsors and Collaborators
AbbVie
Genentech, Inc.
Investigators
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Study Director: AbbVie Inc. AbbVie
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT02203773    
Other Study ID Numbers: M14-358
2014-000687-18 ( EudraCT Number )
First Posted: July 30, 2014    Key Record Dates
Last Update Posted: December 22, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html

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Studies a U.S. FDA-regulated Drug Product: Yes
Product Manufactured in and Exported from the U.S.: No
Keywords provided by AbbVie:
Acute Myelogenous Leukemia
AML
Myelogenous Leukemia
ABT-199
 GDC-0199
Treatment Naive AML
Untreated AML
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Posaconazole
Azacitidine
Decitabine
Venetoclax
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
 Enzyme Inhibitors
Antifungal Agents
Anti-Infective Agents
Trypanocidal Agents
Antiprotozoal Agents
Antiparasitic Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs