Study of Venetoclax in Combination With Carfilzomib and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma (MM)
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| ClinicalTrials.gov Identifier: NCT02899052 |
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Recruitment Status :
Recruiting
First Posted : September 14, 2016
Last Update Posted : August 29, 2022
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Sponsor:
AbbVie
Collaborator:
Genentech, Inc; Onyx Therapeutics, Inc.
Information provided by (Responsible Party):
AbbVie
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Brief Summary:
A Phase 2, open-label, dose escalation study to evaluate the safety and efficacy of venetoclax in combination with carfilzomib-dexamethasone (Kd) in participants with relapsed or refractory MM and have received 1 to 3 prior lines of therapy.
Part 4 of this study is currently enrolling.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Multiple Myeloma | Drug: Carfilzomib Drug: Venetoclax Drug: Dexamethasone | Phase 2 |
Expanded Access : An investigational treatment associated with this study is available outside the clinical trial. More info ...
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 120 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 2, Open-Label, Multi-Center Study of Venetoclax in Combination With Carfilzomib and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma |
| Actual Study Start Date : | January 19, 2017 |
| Estimated Primary Completion Date : | March 25, 2027 |
| Estimated Study Completion Date : | March 25, 2027 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Multiple myeloma
MedlinePlus related topics:
Multiple Myeloma
| Arm | Intervention/treatment |
|---|---|
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Experimental: Venetoclax + Carfilzomib + Dexamethasone
Part 1: Evaluate the safety and pharmacokinetic profiles while providing information to determine the appropriate doses of venetoclax and carfilzomib (VenKd) to be used in the VenKd combination in approximately 18 participants. The dose levels are Venetoclax 400 mg or 800 mg; Carfilzomib 20/27 mg/m2, 20/70 mg/m2, and/or 20/56 mg/m2; Dexamethasone 40 mg Part 2: Further evaluate the safety and efficacy profile of the VenKd combination selected after completion of Part 1 in approximately 22 additional participants. Participants may discontinue Kd but may continue receiving venetoclax once daily (QD) as monotherapy. Part 3: Further evaluation of the efficacy of the VenKd combination after completion of Part 1 and Part 2 in 7 additional participants. Part 4, An additional 65 participants t(11;14) positive will receive varying doses of the VenKd combination or carfilzomib and dexamethasone |
Drug: Carfilzomib
Carfilzomib lyophilized administered intravenously as a 10 to 30 minute infusion in Cycles 1 and beyond within 30 minutes to 4 hours after dexamethasone dosing. Dose level 1 (K1) Cycle 1: 20 mg/m2 on Days 1 and 2, 27 mg/m2 on Days 8, 9, 15, and 16; Cycles 2 - 12: 27 mg/m2 on Days 1, 2, 8, 9, 15, and 16; Cycles 13 - 18: 27 mg/m2 on Days 1, 2, 15, and 16; Cycles 19 and beyond, for participants that have not previously transitioned to monotherapy: 27 mg/m2 on Days 1, 2, 15, and 16. Dose Level K2: Cycle 1: 20 mg/m2 on Day 1; 70 mg/m2 on Days 8 and 15 Cycles 2 - onward: 70 mg/m2 on Days 1, 8, and 15. Dose Level K3: Cycle 1: 20 mg/m2 on Days 1 and 2; 56 mg/m2 on Days 8, 9, 15, and 16. Cycles 2 - onward: 56 mg/m2 on Days 1, 2, 8, 9, 15, and 16. Other Name: Kyprolis Drug: Venetoclax Venetoclax tablet administered orally once daily during Cycles 1 - onward. Venetoclax dose level 1 (Ven1) 400 mg once daily, Ven2 800 mg once daily.
Other Names:
Drug: Dexamethasone Dexamethasone tablet administered orally during Cycles 1 - onward. Dexamethasone dose level 1 (Dex1) 40 mg once weekly, Dex2 40 mg once weekly, Dex3 20 mg twice weekly. |
Primary Outcome Measures :
- Number of Participants with Adverse Events [ Time Frame: First dose of study drug through at least 30 days after end of treatment (approximately 2 years) ]An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
- Very Good Partial Response (VGPR) or Better Response Rate of VenKd in Participants with Relapsed or Refractory Multiple Myeloma (RRMM) as well as Those with t(11;14)-positive RRMM [ Time Frame: First dose of study drug through at least 30 days after end of treatment (approximately 2 years) ]VGPR or better response rate is defined as the percentage of participants with documented VGPR or better based on IMWG criteria.
- Objective Response Rate (ORR) of VenKd in Participants with Relapsed or Refractory Multiple Myeloma (RRMM) as well as Those with t(11;14)-positive RRMM [ Time Frame: First dose of study drug through at least 30 days after end of treatment (approximately 2 years) ]ORR is defined as the percentage of participants with a documented PR or better based on IMWG criteria.
- Complete Response (CR) or Better Rate of VenKd in Participants with Relapsed or Refractory Multiple Myeloma (RRMM) as well as Those with t(11;14)-positive RRMM [ Time Frame: First dose of study drug through at least 30 days after end of treatment (approximately 2 years) ]Complete response or better rate is defined as the percentage of participants with documented CR or better based on IMWG criteria.
Secondary Outcome Measures :
- Very Good Partial Response (VGPR) or Better Response Rate in Participants with Relapsed or Refractory Multiple Myeloma and in a Subset of Participants with High B-cell lymphocyte-2 (BCL-2) Expression [ Time Frame: Up to approximately 17 months ]VGPR or better response rate is defined as the proportion of participants with documented VGPR or better based on IMWG criteria.
- Progression-free survival (PFS) in Participants with Relapsed or Refractory Multiple Myeloma and in a Subset of Participants with High B-cell lymphocyte-2 (BCL-2) Expression [ Time Frame: Up to approximately 17 months ]PFS is defined as the number of days from the date of the first dose of study drug to the date of the first documented progressive disease (PD) or death due to any cause, whichever occurs first.
- Minimal residual disease (MRD) [ Time Frame: Up to 2 years (Screening, Cycle 3 Day 1, and Confirmation of Stringent Complete Response [sCR]/Complete Response [CR]) ]MRD in the bone marrow by next generation sequencing.
- Duration of Overall Response (DOR) in Participants with Relapsed or Refractory Multiple Myeloma and in a Subset of Participants with High B-cell lymphocyte-2 (BCL-2) Expression [ Time Frame: Up to approximately 17 months ]DOR is defined as the number of days from the participant's date of first documented response (PR or better) to the date of first documented PD or death due to MM, whichever occurs first.
- Time to progression (TTP) in Participants with Relapsed or Refractory Multiple Myeloma and in a Subset of Participants with High B-cell lymphocyte-2 (BCL-2) Expression [ Time Frame: Up to approximately 17 months ]TTP is defined as the number of days from the date of the first dose of study drug to the date of first documented PD or death due to MM, whichever occurs first.
- Objective response rate (ORR) in Participants with Relapsed or Refractory Multiple Myeloma and in a Subset of Participants with High B-cell lymphocyte-2 (BCL-2) Expression [ Time Frame: Up to approximately 17 months ]ORR is defined as the proportion of participants with documented partial response (PR) or better based on International Myeloma Working Group (IMWG) criteria.
- Time to Response (TTR) in Participants with Relapsed or Refractory Multiple Myeloma and in a Subset of Participants with High B-cell lymphocyte-2 (BCL-2) Expression [ Time Frame: Up to approximately 17 months ]TTR is defined as the number of days from the date of the first dose of study drug to the date of first documented response (Partial Response (PR) or better).
- Area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) post-dose of Venetoclax [ Time Frame: Approximately 24 hours post-dose on Cycle 1 Days 1 and 15 ]AUC0-24 post-dose of venetoclax.
- Clearance (CL) of Carfilzomib [ Time Frame: Approximately 4 hours post-dose on Cycle 1 Days 1 and 15 ]CL of carfilzomib.
- Terminal Phase Elimination Rate Constant (β) of Carfilzomib [ Time Frame: Approximately 4 hours post-dose on Cycle 1 Days 1 and 15 ]β of carfilzomib.
- AUC from 0 to Infinity (AUC∞) of Carfilzomib [ Time Frame: Approximately 4 hours post-dose on Cycle 1 Days 1 and 15 ]AUC∞ of carfilzomib.
- AUC from Time 0 to the Time of the Last Measurable Concentration (AUCt) of Carfilzomib [ Time Frame: Approximately 4 hours post-dose on Cycle 1 Days 1 and 15 ]AUCt of carfilzomib.
- Maximum Plasma Concentration (Cmax) of Venetoclax [ Time Frame: Approximately 24 hours post-dose on Cycle 1 Days 1 and 15 ]Cmax of venetoclax.
- Cmax of Carfilzomib [ Time Frame: Approximately 4 hours post-dose on Cycle 1 Days 1 and 15 ]Cmax of carfilzomib.
- Terminal Elimination Half-life (t1/2) of Carfilzomib [ Time Frame: Approximately 4 hours post-dose on Cycle 1 Days 1 and 15 ]t1/2 of carfilzomib.
- Time to Maximum Plasma Concentration (Peak Time, Tmax) of Venetoclax [ Time Frame: Approximately 24 hours post-dose on Cycle 1 Days 1 and 15 ](Peak time, Tmax) of venetoclax.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Eastern Collaborative Oncology Group (ECOG) performance score of less than or equal to 2.
- Documented relapsed or progressive Multiple Myeloma (MM) on or after any regimen or is refractory to the most recent line of therapy.
- Positive for translocation t(11;14) as determined by an analytically validated Fluorescent In Situ Hybridization (FISH) assay per central laboratory testing.
- Received prior treatment with at least 1 prior line of therapy for MM.
- Measurable disease on Screening per International Myeloma Working Group (IMWG) criteria.
- Meets absolute neutrophil count, platelet count, hemoglobin, liver and kidney function laboratory values within 2 weeks prior to first dose of study drug.
Exclusion Criteria:
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Has a pre-existing condition that is contraindicated including.
- Non-secretory or oligo-secretory MM
- Active plasma cell leukemia.
- 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.
- Known active Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
- Significant cardiovascular disease.
- Major surgery within 4 weeks prior to first dose.
- Acute infections requiring antibiotic, antifungal or antiviral therapy within14 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 participant's participation in the study.
- History of other active malignancies, including myelodysplastic syndrome (MDS), within the past 3 years prior to study entry Other protocol defined inclusion/exclusion criteria could apply
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): NCT02899052
Contacts
| Contact: ABBVIE CALL CENTER | 844-663-3742 | abbvieclinicaltrials@abbvie.com |
Locations
Show 32 study locations
Sponsors and Collaborators
AbbVie
Genentech, Inc; Onyx Therapeutics, Inc.
Investigators
| Study Director: | ABBVIE INC. | AbbVie |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | AbbVie |
| ClinicalTrials.gov Identifier: | NCT02899052 |
| Other Study ID Numbers: |
M15-538 2019-004340-30 ( EudraCT Number ) |
| First Posted: | September 14, 2016 Key Record Dates |
| Last Update Posted: | August 29, 2022 |
| Last Verified: | August 2022 |
| 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, analyses plans, 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: | For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/ |
| 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 and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/ |
| URL: | https://vivli.org/ourmember/abbvie/ |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
Keywords provided by AbbVie:
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Multiple Myeloma Refractory myeloma Relapsed myeloma Relapsed or Refractory |
Additional relevant MeSH terms:
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Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases |
Dexamethasone Venetoclax Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Antineoplastic Agents |