A Phase 1/2 Study Evaluating the Safety and Pharmacokinetics of ABT-199 in Subjects with Relapsed or Refractory Multiple Myeloma
- Conditions
- Relapsed/refractory multiple myelomaMedDRA version: 16.1Level: HLTClassification code 10028229Term: Multiple myelomasSystem Organ Class: 100000004851Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-000589-38-BE
- Lead Sponsor
- AbbVie Deutschland GmbH & Co. KG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 166
1. Subject must be = 18 years of age.
2. Subject has an ECOG performance score of = 1.
- For subjects in phase 2 portion: ECOG performance score of = 2.
3. Diagnosis of multiple myeloma which requires treatment and has been previously treated with:
- For subjects in the Dose Escalation portion of the study:
o = 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 portion of the study:
o 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 Combination Portion:
? Have received treatment with a proteasome inhibitor and an immunomodulatory (IMiD®) agent (e.g., thalidomide, lenalidomide, pomalidomide), AND
? Have MM positive for 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:
? Subject must have documented MM positive for the t(11;14) translocation. If testing has been performed by a laboratory other than the Sponsor-directed central laboratory, subjects may be enrolled but must be re-tested
by the central laboratory for confirmation of t(11;14) status. The investigator should ensure that the testing is consistent with local guidelines and clinical practice, and the test uses either 1) plasma cell enriched or 2) cytoplasmic immunoglobulin-enhanced interphase fluorescence in-situ hybridization (FISH) analysis of bone marrow aspirate
samples per International Myeloma Working Group (IMWG) guidelines 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 3 lines of therapy, including an immunomodulatory drug (lenalidomide or pomalidomide), a proteasome inhibitor (bortezomib, carfilzomib or ixazomib), daratumumab, and glucocorticoids. Daratumumab combination regimen must be one of the prior lines of therapy (for this study, daratamumab plus corticosteroids will not be considered a combination regimen).
4. 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.
5. 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-vs-host disease (GVHD) i.e requiring treatment.
6. Subjects must meet certain laboratory parameters (refer to protocol for parameters).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 112
F.1.3 Eld
1. Subject exhibits evidence of other clinically significant uncontrolled condition(s), including, but not limited to: uncontrolled systemic infection (viral, bacterial, or fungal), diagnosis of fever and neutropenia within 1 week prior to first dose of study drug.
2. Subject has a cardiovascular disability status of New York Heart Association Class = 3.
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.
4. 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;
- 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.
5. Known Human Immunodeficiency Viral (HIV) infection
6. Active hepatitis B or C infection based on screening blood testing.
7. Subject is receiving other ongoing anti-myeloma therapy.
8. 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
9. Subject has received any of the following within 14 days prior to the first dose of study drug or has not recovered to less than a Grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy: any anti-myeloma therapy including chemotherapy, radiotherapy, or investigational therapy, including targeted small molecule agents.
10. Subject has received prior treatment with a BCL-2 family inhibitor.
11. Subject is pregnant, parturient, or breastfeeding; deprived of freedom by judicial or administrative decision; hospitalized and unable to provide consent, or otherwise unable to provide consent.
12. Subject has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or star fruit within 3 days prior to the first dose of study drug.
13. Subject has received immunization with live vaccine within 60 days of dosing.
14. Recent corticosteroid therapy at a cumulative dose equivalent to > 140 mg of prednisone or a single dose equivalent to = 40 mg/day of dexamethasone within 2 weeks prior to the first dose of study drug.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method