Study Evaluating ABT-199 in Subjects With Relapsed or Refractory Multiple Myeloma

Overview

  • Study type

    Interventional
  • Study phase

    I/II
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Rochester, Minnesota: 12-005388
    • Scottsdale/Phoenix, Arizona: 12-005388
    • Jacksonville, Florida: 12-005388
    NCT ID: NCT01794520
    Sponsor Protocol Number: M13-367

About this study

The phase 1 primary objectives of this study are to assess the safety profile, characterize pharmacokinetics (PK) and determine the dosing schedule, maximum tolerated dose (MTD), and recommended phase 2 dose (RPTD) of ABT-199 (venetoclax) when administered in subjects with relapsed or refractory multiple myeloma. This study will also assess the safety profile and PK of venetoclax in combination with dexamethasone in subjects with t(11;14)-positive multiple myeloma. The phase 2 primary objective is to further evaluate the objective response rate (ORR) and very good partial response or better rate (VGPR+) in subjects with t(11;14)-positive multiple myeloma and to evaluate patient reported outcomes.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria:

  • Subject must be ≥ 18 years of age.
  • Subject has an ECOG performance score of ≤ 1.  
    • For subjects in the Phase 2 portion: ECOG performance score of ≤ 2.
  • Diagnosis of multiple myeloma which requires treatment and has been previously treated with:
    • For subjects in the Dose Escalation cohort of the study:
      • ≥ 1 prior line of therapy. Induction therapy followed by stem cell transplant and maintenance therapy will be considered as a single line of therapy.
    • For subjects in the Safety Expansion cohort of the study:
      • Have received treatment with a proteasome inhibitor and an immunomodulatory (IMiD®) agent (e.g., thalidomide, lenalidomide, pomalidomide). Induction therapy followed by stem cell transplant and maintenance therapy will be considered as a single line of therapy.
    • For subjects in the Venetoclax-Dexamethasone (VenDex) Combination cohort of the study:
      • Have received treatment with a proteasome inhibitor and an immunomodulatory (IMiD®) agent (e.g., thalidomide, lenalidomide, pomalidomide). Induction therapy followed by stem cell transplant and maintenance therapy will be considered as a single line of therapy; AND
      • Have MM positive for the t(11;14) translocation, as determined by an analytically validated fluorescence in situ hybridization (FISH) assay per the central laboratory testing.
    • For subjects in the Phase 2 cohort of the study:
      • Have MM positive for the t(11;14) translocation, as determined by an analytically validated fluorescence in situ hybridization (FISH) assay per central laboratory testing (enrollment with local t(11;14)-positive FISH results will be considered at the discretion of the TA MD); AND
      • Subject must have evidence of disease progression on or within 60 days of the last dose of the most recent previous treatment regimen based on the IMWG criteria; AND
      • Subject must have previously received at least 2 lines of therapy, including an immunomodulatory drug (lenalidomide or pomalidomide), a proteasome inhibitor (bortezomib, carfilzomib or ixazomib), daratumumab, and glucocorticoids.
    • For United States (US) Subjects: Daratumumab combination regimen must be one of the prior lines of therapy (for this study, daratumumab plus corticosteroids will not be considered a combination regimen).
    • For Non-US Subjects: Either daratumumab monotherapy or daratumumab combination therapy is acceptable. Daratumumab monotherapy will be limited to approximately 20 percent of the total number of Phase 2 subjects.
  • Subject must have measurable disease at Screening, defined as any of the following:
    • Serum monoclonal protein ≥ 1.0 g/dL (≥ 10 g/L) by protein electrophoresis;
    •  ≥ 200 mg of monoclonal protein in the urine on 24-hour electrophoresis; or
    • Serum immunoglobulin free light chain (FLC) ≥ 10 mg/dL provided serum FLC ratio is abnormal.
  • Subjects with a history of autologous or allogenic stem cell transplantation must have adequate peripheral blood counts independent of any growth factor support, and have recovered from any transplant-related toxicity(s) and be:
    • 100 days post-autologous transplant (prior to first dose of study drug); or
    •  ≥ 6 months post-allogenic transplant (prior to first dose of study drug) and not have active graft-versus-host disease (GVHD); i.e., requiring treatment.
  • Subjects must meet the following laboratory parameters, per laboratory reference range, at least once during screening period:
    • ANC ≥ 1000/μL;
    • Subjects may use growth factor support to achieve ANC eligibility criteria;
    • AST and ALT ≤3 × upper limit of normal range (ULN);
    • Calculated creatinine clearance ≥30 mL/min using a modified Cockcroft-Gault calculation or a 24-hour urine collection for Creatinine Clearance:
      • eCCr = (140 –Age) ● weight (kg) ● [0.85 if Female]
                      72 ● Serum Creatinine (mg/dL)
    • OR, if serum creatinine is in μmol/L:
      • eCCr = (140 –Age) ● weight (kg) ● [1.23 if Male, 1.04 if Female]
                              Serum Creatinine (μmol/L)
    • Platelet count ≥30,000 mm3, independent of transfusion for 2 weeks.
    • Hemoglobin ≥8.0 g/dL, subjects may receive blood transfusion to achieve hemoglobin eligibility criteria per investigator discretion.
    • Total bilirubin ≤1.5 × ULN.
    • Subjects with Gilbert's Syndrome may have bilirubin > 1.5 × ULN.

Exclusion Criteria:

  • Subject exhibits evidence of other clinically significant uncontrolled condition(s), including, but not limited to:
    • Acute infection within 14 days prior to first dose of study drug requiring antibiotic, antifungal, or antiviral therapy;
    • Diagnosis of fever and neutropenia within 1 week prior to first dose of study drug.
  • Subject has a cardiovascular disability status of New York Heart Association Class ≥ 3.
  • Subject has a significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, cardiovascular or hepatic disease within the last 6 months that, in the opinion of the investigator, would adversely affect his/her participation in the study.
  • Subject has a history of other active malignancies other than multiple myeloma within the past 3 years prior to study entry, with the following exceptions:
    • Adequately treated in situ carcinoma of the cervix uteri;
    • Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
    • Localized prostate cancer Gleason grade 6 or lower AND with stable Prostate Specific Antigen (PSA) levels off treatment;
    • Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
  • Known Human Immunodeficiency Viral (HIV) infection.
  • Active hepatitis B or C infection based on screening blood testing.
  • Subject is receiving other ongoing anti-myeloma therapy.
  • Subject has received any of the following within 7 days prior to the first dose of study drug:
    • Strong or moderate CYP3A inhibitors; or
    • Strong or moderate CYP3A inducers.

 

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Shaji Kumar, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Shaji Kumar, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Shaji Kumar, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

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Study Results Summary

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Supplemental Study Information

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Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

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