Condition or disease | Intervention/treatment | Phase |
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Plasma Cell Myeloma | Drug: Bortezomib Biological: Daratumumab Drug: Dexamethasone Drug: Ixazomib | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 76 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Randomized Phase II Study of DaRatumumab, Ixazomib, and Dexamethasone vs Daratumumab, Bortezomib (VElcade) and Dexamethasone Followed by Daratumumab-Ixazomib-Dexamethasone in Newly Diagnosed Multiple Myeloma (DeRIVE Study) |
Actual Study Start Date : | July 3, 2019 |
Estimated Primary Completion Date : | July 31, 2024 |
Estimated Study Completion Date : | July 31, 2024 |
Arm | Intervention/treatment |
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Experimental: Arm I (DId)
INDUCTION: Patients receive dexamethasone IV and PO on days 1, 8, 15, and 22, daratumumab IV on days 1, 8, 15, and 22 of cycles 1-2 and on days 1 and 15 of cycles 3-8, and ixazomib PO on days 1, 8, and 15. Treatment repeats every 28 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Eligible patients then undergo stem cell transplant per standard of care. Patients who have at least stable disease after induction and patients who have undergone transplant continue to Maintenance. MAINTENANCE: Patients receive dexamethasone IV and PO on days 1, 8, 15, and 22, daratumumab IV on day 1, and ixazomib PO on days 1, 8, and 15. Cycles repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity. |
Biological: Daratumumab
Given IV
Other Names:
Drug: Dexamethasone Given IV and PO
Other Names:
Drug: Ixazomib Given PO
Other Names:
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Experimental: Arm II (DVd, DId)
INDUCTION CYCLES 1-3: Patients receive dexamethasone IV and PO on days 1, 8, and 15, daratumumab IV on days 1, 8, and 15, and bortezomib subcutaneously (SC) on days 1, 4, 8, and 11. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. INDUCTION CYCLES 4-8: Patients receive dexamethasone IV and PO on days 1, 8, 15, and 22, daratumumab IV on days 1 and 15, and ixazomib PO on days 1, 8, and 15. Treatment repeats every 28 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Eligible patients then undergo stem cell transplant per standard of care. Patients who have at least stable disease after induction and patients who have undergone transplant continue to Maintenance. MAINTENANCE: Patients receive dexamethasone IV on day 1, daratumumab IV on day 1, and ixazomib PO on days 1, 8, and 15. Cycles repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity. |
Drug: Bortezomib
Given SC
Other Names:
Biological: Daratumumab Given IV
Other Names:
Drug: Dexamethasone Given IV and PO
Other Names:
Drug: Ixazomib Given PO
Other Names:
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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Have documented multiple myeloma as defined by the International Myeloma Working Group (IMWG) 2014 criteria including: Clonal bone marrow plasma cells ≥ 10% (If bone marrow has less than 10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement). In addition, the patient must meet one of the criteria in d1 or d2:
Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically (one or more of the following):
Bone lesions: 1 or more osteolytic lesions on skeletal radiography, computed tomography (CT), or magnetic resonance imaging (MRI)
Any one or more of the following:
Clonal bone marrow plasma cell percentage ≥ 60%
Involved:uninvolved serum free light chain (FLC) ratio > 100
Measurable disease as defined by any of the following:
Female patients who:
Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following:
Exclusion Criteria:
Known significant cardiac abnormalities including:
Contact: Ajay Nooka, MD, MPH | 404-778-3612 | anooka@emory.edu |
United States, Georgia | |
Emory University Hospital/Winship Cancer Institute | Recruiting |
Atlanta, Georgia, United States, 30322 | |
Contact: Shondolyn Richburg 404-778-3612 shondolyn.k.richburg@emory.edu | |
Contact: Mikayla Williams 404-778-4713 mikayla.williams@emory.edu |
Principal Investigator: | Ajay Nooka, MD, MPH | Emory University |
Tracking Information | |||||
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First Submitted Date ICMJE | May 7, 2019 | ||||
First Posted Date ICMJE | May 8, 2019 | ||||
Last Update Posted Date | December 8, 2020 | ||||
Actual Study Start Date ICMJE | July 3, 2019 | ||||
Estimated Primary Completion Date | July 31, 2024 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
≥ Very good partial response (VGPR) response rate [ Time Frame: After cycle 8 (224 days) ] This will be defined as the proportion of subjects who achieved a response of VGPR or better (stringent complete response [sCR], complete response [CR], or VGPR) after induction cycle 8 treatment. Response will be determined by modified International Myeloma Working Group (IMWG) criteria.
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Original Primary Outcome Measures ICMJE | Same as current | ||||
Change History | |||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title ICMJE | Daratumumab, Ixazomib, & Dexamethasone or Daratumumab, Bortezomib, & Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma | ||||
Official Title ICMJE | A Randomized Phase II Study of DaRatumumab, Ixazomib, and Dexamethasone vs Daratumumab, Bortezomib (VElcade) and Dexamethasone Followed by Daratumumab-Ixazomib-Dexamethasone in Newly Diagnosed Multiple Myeloma (DeRIVE Study) | ||||
Brief Summary | This phase II trial studies how well daratumumab, ixazomib, and dexamethasone with or without bortezomib work in treating patients with newly diagnosed multiple myeloma. Immunotherapy with monoclonal antibodies, such as daratumumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as ixazomib, dexamethasone, and bortezomib, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving daratumumab, ixazomib, and dexamethasone with or without bortezomib may work better in treating patients with multiple myeloma. | ||||
Detailed Description |
PRIMARY OBJECTIVE: I. To determine the ≥ very good partial response (VGPR) rate after 8 cycles in subjects treated with daratumumab, ixazomib and dexamethasone (DId) versus (vs) daratumumab, bortezomib and dexamethasone (DVd) followed by DId among newly diagnosed myeloma patients (NDMM). SECONDARY OBJECTIVES: I. To estimate the proportion of subjects with successful stem cell mobilization after receiving 3 cycles of treatment in both arms (DId x 8 vs DVd x 3 then DId x 5). II. To establish safety among patients receiving the combination of DId and DVd then DId. III. To obtain anti-tumor activity (best response rates: overall response rate [ORR], VGPR, complete response [CR], stringent complete response [sCR] and minimal residual of disease [MRD] negativity) in patients treated with these combinations. IV. Progression free survival (PFS), progression free survival 2 (PFS2), duration of response (DOR), time to progression (TTP), determine the time to next therapy (TTNT). V. Overall survival (OS). VI. Engraftment parameters among the autologous stem cell transplant (ASCT) group. VII. Determine whether tumor response and PFS may change in subgroups with different prognosis according to current prognostic factors. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: INDUCTION: Patients receive dexamethasone intravenously (IV) and orally (PO) on days 1, 8, 15, and 22, daratumumab IV on days 1, 8, 15, and 22 of cycles 1-2 and on days 1 and 15 of cycles 3-8, and ixazomib PO on days 1, 8, and 15. Treatment repeats every 28 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Eligible patients then undergo stem cell transplant per standard of care. Patients who have at least stable disease after induction and patients who have undergone transplant continue to Maintenance. MAINTENANCE: Patients receive dexamethasone IV and PO on days 1, 8, 15, and 22, daratumumab IV on day 1, and ixazomib PO on days 1, 8, and 15. Cycles repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity. ARM II: INDUCTION CYCLES 1-3: Patients receive dexamethasone IV and PO on days 1, 8, and 15, daratumumab IV on days 1, 8, and 15, and bortezomib subcutaneously (SC) on days 1, 4, 8, and 11. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. INDUCTION CYCLES 4-8: Patients receive dexamethasone IV and PO on days 1, 8, 15, and 22, daratumumab IV on days 1 and 15, and ixazomib PO on days 1, 8, and 15. Treatment repeats every 28 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Eligible patients then undergo stem cell transplant per standard of care. Patients who have at least stable disease after induction and patients who have undergone transplant continue to Maintenance. MAINTENANCE: Patients receive dexamethasone IV on day 1, daratumumab IV on day 1, and ixazomib PO on days 1, 8, and 15. Cycles repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months. |
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Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 2 | ||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE | Plasma Cell Myeloma | ||||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Recruiting | ||||
Estimated Enrollment ICMJE |
76 | ||||
Original Estimated Enrollment ICMJE | Same as current | ||||
Estimated Study Completion Date ICMJE | July 31, 2024 | ||||
Estimated Primary Completion Date | July 31, 2024 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE |
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Listed Location Countries ICMJE | United States | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT03942224 | ||||
Other Study ID Numbers ICMJE | IRB00102336 NCI-2018-03615 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) Winship4547-18 ( Other Identifier: Emory University Hospital/Winship Cancer Institute ) |
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Has Data Monitoring Committee | Yes | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | Ajay Nooka, Emory University | ||||
Study Sponsor ICMJE | Emory University | ||||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | Emory University | ||||
Verification Date | December 2020 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |