Study of Venetoclax in Combination With Carfilzomib and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma (MM)
- Conditions
- Multiple MyelomaMedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-004340-30-HU
- Lead Sponsor
- AbbVie Deutschland GmbH & Co. KG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 120
1. Eastern Cooperative Oncology Group (ECOG) performance score of = 2.
2. Subject has documented RRMM on or after any regimen or is refractory to the most recent line of therapy.
- Relapsed myeloma is defined as previously treated myeloma that progresses and requires initiation of salvage therapy, but does not meet criteria for refractory myeloma.
- Refractory myeloma is defined as disease that is nonresponsive (failure to achieve minimal response or development of progressive disease [PD]) while on primary or salvage therapy, or progresses within 60 days of last therapy.
- For Part 4, subjects must meet the above criteria and also be positive for translocation t(11;14) as determined by an analytically validated Fluorescent In Situ Hybridization (FISH) assay per central laboratory testing.
3. Subject has received prior treatment with at least one prior line of therapy for MM.
- Parts 1, 2, 3: Subject has received prior treatment with one to three prior lines of therapy.
- Part 4: Subject has received prior treatment with at least one prior line of therapy.
- A line of therapy consists of = 1 complete cycle of a single agent, a regimen consisting of a combination of several drugs, or a planned sequential therapy of various regimens.
4. Subject has measurable disease at Screening, defined as at least one of the following:
- Serum M-protein = 0.5 g/dL (= 5 g/L), OR
- Urine M-protein = 200 mg/24 hours, OR
- Serum free light chain (FLC) = 10 mg/dL, provided serum FLC ratio is abnormal.
5. Subject must meet the following laboratory parameters within 2 weeks prior to first dose, per laboratory reference range:
- Absolute neutrophil count (ANC) = 1000/µL; subject may use growth factor support to achieve ANC eligibility criteria.
- Platelet count:
o = 50,000/mm3 for subject with = 50% myeloma involvement in the bone marrow;
o = 30,000/mm3 for subject with > 50% myeloma involvement in the bone marrow;
o Subject may not have received a platelet transfusion within 72 hours prior to the platelet count used for eligibility.
- Hemoglobin = 8.0 g/dL; subject may receive red blood cell (RBC) transfusions in accordance with institutional guidelines to meet this criteria.
- AST and ALT = 3 × upper limit of normal (ULN).
- Total bilirubin = 1.5 × ULN; subject with documented Gilbert's syndrome may have bilirubin > 1.5 × ULN with the approval of the Primary Therapeutic Area Medical Director.
- Creatinine clearance = 30 mL/min, measured by 24-hour urine collection or calculated using the Cockcroft-Gault formula.
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 48
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 72
1. Subject has any of the following conditions:
- Non-secretory or oligo-secretory MM
- Active plasma cell leukemia, i.e., either 20% of peripheral white blood cells or > 2.0 × 109/L circulating plasma cells by standard differential
- Waldenström's macroglobulinemia
- Primary amyloidosis
- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Active hepatitis B or C infection based on screening blood testing
- Significant cardiovascular disease, including uncontrolled angina, hypertension, arrhythmia, recent myocardial infarction within 6 months of first dose, congestive heart failure New York Heart Association (NYHA) Class = 3, and/or left ventricular ejection fraction = 40% as assessed by multiple gated acquisition scan (MUGA) or ECHO.
- Major surgery within 4 weeks prior to first dose
- Acute infections requiring antibiotic, antifungal, or antiviral therapy within 14 days prior to first dose.
- Peripheral neuropathy = Grade 3 or = Grade 2 with pain within 2 weeks prior to first dose
- Uncontrolled diabetes or uncontrolled hypertension within 14 days prior to first dose
- Any other medical condition that, in the opinion of the Investigator, would adversely affect the subject's participation in the study.
2. Subject has a history of other active malignancies, including myelodysplastic syndrome (MDS), within the past 3 years prior to study entry, with the following exceptions:
- Adequately treated in situ carcinoma of the cervix uteri or the breast,
- 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 with no evidence of disease confined and surgically resected (or treated with other modalities) with curative intent and unlikely to impact survival during the duration of the study.
3. If subject had a prior allogeneic stem cell transplant (SCT), subject has evidence of ongoing graft-versus-host disease (GvHD).
4. Subject has had prior treatment with carfilzomib or has a hypersensitivity or allergy to captisol (a cyclodextrin derivative used to solubilize carfilzomib) or dexamethasone.
5. Subject is refractory to any BCL-2 family inhibitor.
6. Subject has been treated or received any of the following:
- Allogeneic or syngeneic SCT within 6 months prior to first dose.
- Autologous SCT within 12 weeks prior to first dose.
- Immunization with live vaccine within 8 weeks prior to first dose.
- Monoclonal antibodies within 6 weeks prior to first dose.
- Any anti-myeloma therapy (other than monoclonal antibodies), including chemotherapy, radiotherapy, biological, immunotherapy or an investigational therapy, including targeted small molecule agents within 5 half-lives (or 14 days if half-life is unknown) prior to first dose.
- Corticosteroid therapy at a dose equivalent to = 4 mg/day of dexamethasone within 3 weeks prior to first dose.
- A strong or moderate CYP3A inhibitor or inducer within 1 week prior to first dose.
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