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| ID | Type | Description | Link |
|---|---|---|---|
| 2021-003284-10 | EudraCT Number |
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| Name | Class |
|---|---|
| Janssen Research & Development, LLC | INDUSTRY |
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The purpose of this study is to compare the efficacy of Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) followed by Ciltacabtagene Autoleucel versus Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) followed by Autologous Stem Cell Transplant (ASCT) in newly diagnosed multiple myeloma patients.
Multiple myeloma (MM) is a malignant plasma cell disorder characterized by the production of monoclonal immunoglobulin (Ig) proteins or protein fragments (M proteins) that have lost their function.
JNJ-68284528 (ciltacabtagene autoleucel [cilta-cel]) is an autologous chimeric antigen receptor T cell (CAR-T) therapy that targets B-cell maturation antigen (BCMA) that is being evaluated to treat participants with multiple myeloma. The primary hypothesis is that in transplant-eligible participants with newly diagnosed multiple myeloma (NDMM), cilta-cel will significantly improve progression-free survival (PFS) and Sustained MRD-negative CR rate compared with Autologous Stem Cell Transplant (ASCT).
Approximately 750 participants (375 per arm) will be randomly assigned in a 1:1 ratio into 2 arms.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A: DVRd + ASCT+DVRd (Standard Therapy) | Active Comparator | Participants will receive daratumumab, bortezomib, lenalidomide and dexamethasone (DVRd) for 4 induction cycles. Followed by ASCT and 2 cycles of DVRd consolidation, and lenalidomide maintenance therapy for 2 years Daratumumab subcutaneously (SC), 1800 mg on days 1, 8, 15 and 22 of cycle 1 and 2, on days 1 and 15 of cycle 3-6. Bortezomib SC 1.3 mg/m^2 on days 1, 4, 8, and 11 of each cycle 1-6. Lenalidomide orally, 25 mg on days 1 to 21 of each cycle 1-6. Dexamethasone orally, 40 mg once a week on days 1, 8, 15 and 22 of each cycle 1-6. Each cycle will consist 28 days. Lenalidomide maintenance orally 10 to 15 mg on days 1 to 28 (continuously) until confirmed progressive disease or unacceptable toxicity or for a maximum of 2 years |
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| Arm B: DVRd followed by Ciltacabtagene Autoleucel | Experimental | Participants will receive daratumumab, bortezomib, lenalidomide and dexamethasone (DVRd) for 6 induction cycles. Participants will receive a conditioning regimen (cyclophosphamide 300 mg/m^2 intravenous [IV] and fludarabine 30 mg/m^2 IV daily for 3 days) and Cilta-cel infusion 0.75*10^6 chimeric antigen receptor (CAR)-positive viable T cells/kilogram (kg), followed by lenalidomide post CAR-T cell therapy for 2 years Daratumumab subcutaneously (SC), 1800 mg on days 1, 8, 15 and 22 of cycle 1 and 2, on days 1 and 15 of cycle 3-6. Bortezomib SC 1.3 mg/m^2 on days 1, 4, 8, and 11 of each cycle 1-6. Lenalidomide orally, 25 mg on days 1 to 21 of each cycle 1-6. Dexamethasone orally, 40 mg once a week on days 1, 8, 15 and 22 of each cycle 1-6. Each cycle will consist of 28 days. Lenalidomide maintenance orally 10 to 15 mg on days 1 to 28 (continuously) until confirmed progressive disease or unacceptable toxicity or for a maximum of 2 years |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Daratumumab | Drug | Daratumumab will be administered SC. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Progression free survival (PFS) | Progression free survival is defined as the time from the date of randomization to the date of first documented PD, as defined in the IMWG criteria, or death due to any cause, whichever occurs first | up to 10 years ( or 300 PFS events) |
| Sustained MRD-negative CR | Sustained MRD-negative CR is defined as being MRD negative by bone marrow aspirate, as determined by NGS with a sensitivity of at least 10-5, and meeting the IMWG criteria for CR, and with MRD-negativity status confirmed at a minimum 12 months apart and without any examination showing MRD-positive status or PD in between. | up to 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response (OR) | OR is defined as participants who achieve a partial response (PR) or better according to the IMWG criteria. | up to 17 years |
| Complete Response (CR) or better status | CR or better is defined as percentage of participants who achieve a CR response or Stringent Complete Response (sCR) response according to the IMWG criteria. |
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Inclusion Criteria:
Participants with documented NDMM according to IMWG diagnostic criteria, for whom high-dose therapy and ASCT are part of the intended initial treatment plan.
Measurable disease, as assessed by central laboratory, at screening as defined by any of the following:
ECOG performance status of grade 0 or 1
Clinical laboratory values within prespecified range.
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Arkansas | Little Rock | Arkansas | 72205 | United States | ||
| City of Hope |
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| Bortezomib | Drug | Bortezomib will be administered SC. |
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| Lenalidomide | Drug | Lenalidomide will be administered orally. |
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| Dexamethasone | Drug | Dexamethasone will be administered orally. |
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| Cilta-cel | Drug | Cilta-cel will be administered intravenously |
|
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| Cyclophosphamide | Drug | Cyclophosphamide will be administered intravenously. |
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| Fludarabine | Drug | Fludarabine will be administered intravenously. |
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| up to 17 years |
| Overall Minimal Residual Disease (MRD) -negative CR | achieving MRD-negative CR, as determined by NGS at any time after the date of randomization before initiation of subsequent antimyeloma therapy. | up to 17 years |
| Time to subsequent antimyeloma therapy | Time to subsequent anti-myeloma therapy is defined as the time from randomization to the start of subsequent anti-myeloma therapy. | up to 17 years |
| Progression Free Survival on Next-line Therapy (PFS2) | the time from the date of randomization to the date of event, defined as PD as assessed by investigator that starts after the next line of subsequent therapy, or death due to any cause, whichever occurs first. | up to 17 years |
| Overall Survival (OS) | Overall survival is measured from the date of randomization to the date of the participant's death. | up to 17 years |
| Change from Baseline in Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30) Scale Score | The EORTC QLQ-C30 includes 30 items in 5 functional scales (physical, role, emotional, cognitive, and social), 1 global health status scale, 3 symptom scales (pain, fatigue, nausea/vomiting), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The responses are reported using a verbal rating scale. The item and scale scores are transformed to a 0 to 100 scale. A higher score represents greater HRQoL, better functioning, and more (worse) symptoms. | up to 17 years |
| Change from Baseline in Health-Related Quality of Life as Assessed by MySIm-Q Scale Score | The MySIm-Q is a disease-specific PRO assessment complementary to the EORTC-QLQ-C30. It includes 17 items with recall period of "7 days" and responses are reported on a 5-point verbal rating scale. Item responses are scored from 0 to 4. Higher scores indicate greater severity/impact. | up to 17 years |
| Change from Baseline in Health-Related Quality of Life as Assessed by European Quality of Life - 5 Dimensions-5 Levels (EQ-5D-5L) Scale Scor | The EQ-5D-5L is a generic measure of health status. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each of the 5 dimensions is divided into 5 levels of perceived problems, where Level 1: no problem, Level 2: slight problems, Level 3: moderate problems, Level 4: severe problems and Level 5: extreme problems, plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). | up to 17 years |
| Change from Baseline in Health-Related Quality of Life as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score | The PGIS uses 2 items to assess the participant's perception of the severity of their disease symptoms and impact using a 5-point verbal rating scale. Score ranges from 1 (None) to 5 (Very Severe). | up to 17 years |
| Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) | The National Cancer Institute's PRO-CTCAE is an item library of common adverse events experienced by people with cancer that are appropriate for self-reporting. Each symptom selected for inclusion can be rated by up to 3 attributes characterizing the presence/frequency, severity, and/or interference that ranges from 0 to 4 with higher scores indicating higher frequency or greater severity/impact. | up to 280 days |
| Duarte |
| California |
| 91010 |
| United States |
| UC San Diego Health Moores Cancer Center | San Diego | California | 92093 | United States |
| University of California San Francisco (UCSF) | San Francisco | California | 94117 | United States |
| Stanford University | Stanford | California | 94305 | United States |
| Moffit Cancer Center | Tampa | Florida | 33612 | United States |
| Emory University Hospital | Atlanta | Georgia | 30322 | United States |
| University of Chicago | Chicago | Illinois | 60637 | United States |
| University of Iowa | Iowa City | Iowa | 52242 | United States |
| University Of Maryland Medical Center | Baltimore | Maryland | 21201 | United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| Boston Medical Center | Boston | Massachusetts | 02118 | United States |
| Dana-Farber Cancer Institute | Boston | Massachusetts | 02215 | United States |
| Karmanos Cancer Center | Detroit | Michigan | 48201 | United States |
| Mount Sinai Medical Center | New York | New York | 10029 | United States |
| Memorial Sloan-Kettering Cancer Center | New York | New York | 10065 | United States |
| University of Rochester | Rochester | New York | 14642 | United States |
| Montefiore M-E Center | The Bronx | New York | 10467 | United States |
| Levine Cancer Institute | Charlotte | North Carolina | 28204 | United States |
| Duke University Medical Center | Durham | North Carolina | 27705 | United States |
| Cleveland Clinic | Cleveland | Ohio | 44195 | United States |
| The Ohio State University | Columbus | Ohio | 43210 | United States |
| Thomas Jefferson University Hospital | Philadelphia | Pennsylvania | 19107 | United States |
| University of Texas Southwestern Medical Center | Dallas | Texas | 75390 | United States |
| University of Virginia | Charlottesville | Virginia | 22903 | United States |
| University of Washington Medical | Seattle | Washington | 98195 | United States |
| Medical College Wisconsin | Milwaukee | Wisconsin | 53226 | United States |
| Princess Alexandra Hospital | Brisbane | Australia |
| Royal Prince Alfred Hospital | Camperdown | Australia |
| Royal Brisbane and Womens Hospital | Herston | Australia |
| Alfred Health | Melbourne | Australia |
| Austin Hospital | Melbourne | Australia |
| Peter MacCallum Cancer Centre | Melbourne | Australia |
| Fiona Stanley Hospital | Murdoch | Australia |
| Calvary Mater Newcastle Hospital | Waratah | Australia |
| Westmead Hospital | Westmead | Australia |
| Jules Bordet Instituut | Anderlecht | Belgium |
| UZA | Antwerp | Belgium |
| UZ Gent | Ghent | Belgium |
| UZ Leuven | Leuven | Belgium |
| Cross Cancer Institute | Edmonton | Canada |
| McMaster University | Hamilton | Canada |
| Hopital Maisonneuve-Rosemont | Montreal | Canada |
| Mcgill University Health Centre | Montreal | Canada |
| Ottawa Hospital Research Institute | Ottawa | Canada |
| (CHU) Centre Hospitalier Universitaire de Quebec Laval | Québec | Canada |
| Princess Margaret Cancer Centre | Toronto | Canada |
| Vancouver General Hospital | Vancouver | Canada |
| Fakultni nemocnice Brno | Brno | Czechia |
| Fakultni nemocnice Hradec Kralove | Králová | Czechia |
| Fakutni nemocnice Ostrava | Ostrava | Czechia |
| Fakultni nemocnice Plzen | Pilsen | Czechia |
| CHRU de Lille - Hopital Claude Huriez | Lille | France |
| Hospices Civils De Lyon | Lyon | France |
| CHU De Nantes - Hématologie Clinique | Nantes | France |
| CHU Poitiers - Pôle régional de Cancérologie | Poitiers | France |
| Hopital Saint Louis - Aphp Hôpitaux Universitaires Saint-Louis | Saint-Louis | France |
| CHU de Toulouse | Toulouse | France |
| University Hospital of Cologne | Cologne | Germany |
| Universitätsklinikum Hamburg - Eppendorf | Hamburg | Germany |
| University Hospital of Leipzig | Leipzig | Germany |
| Tübingen | Tübingen | Germany |
| University Hospital of Würzburg | Würzburg | Germany |
| Attikon University General Hospital of Attica | Athens | Greece |
| 'G. Papanikolaou' Hospital of Thessaloniki | Thessaloniki | Greece |
| Hadassah Medical Center | Jerusalem | Israel |
| Sheba medical center | Ramat Gan | Israel |
| Tel Aviv Sourasky Medical Center | Tel Aviv | Israel |
| Juntendo University Hospital | Bunkyō City | Japan |
| Kyushu University Hospital - Hematology/Oncology | Fukuoka | Japan |
| Hokkaido University Hospital-Department of Hematology | Hokkaido | Japan |
| Hyogo College of Medicine | Hyōgo | Japan |
| Kanazawa University Hospital | Kanazawa | Japan |
| Nagoya City University Hospital - Department of Hematology & Oncology | Nagoya | Japan |
| Okayama University Hospital - Hematology/Oncology | Okayama | Japan |
| Osaka metropolitan university hospital | Osaka | Japan |
| Japanese Red Cross Medical Center - Hematology | Shibuya City | Japan |
| Keio University Hospital - Hematology | Shinjuku-Ku | Japan |
| Tohoku University Hospital - Hematology | Tōhoku | Japan |
| VU Medisch Centrum | Amsterdam | Netherlands |
| University Medical Center Groningen | Groningen | Netherlands |
| Radboud UMC | Nijmegen | Netherlands |
| Erasmus MC | Rotterdam | Netherlands |
| UMC Utrecht | Utrecht | Netherlands |
| Oslo University Hospital Ullevål - Oncology | Oslo | Norway |
| Hospital Universitario Germans Trias i Pujol | Badalona | Spain |
| Hospital Clinic de Barcelona | Barcelona | Spain |
| Instituto Catalán de Oncología | Barcelona | Spain |
| Hospital Universitario Ramón y Cajal | Madrid | 28034 | Spain |
| Hospital General Universitario Gregorio Marañón | Madrid | Spain |
| Hospital Universitario 12 de Octubre | Madrid | Spain |
| CLINICA UNIV. DE NAVARRA, Pamplona | Pamplona | Spain |
| Hospital Universitario de Salamanca | Salamanca | Spain |
| Hospital de Santiago de Compostela | Santiago de Compostela | Spain |
| Hospital Universitario Virgen del Rocío | Seville | Spain |
| Hospital Universitario la Fe, Valencia | Valencia | Spain |
| Sahlgrenska Universitetssjukhuset | Gothenburg | Sweden |
| Landstinget i Ostergotland-Universitetssjukhuset i Linkoping | Linköping | Sweden |
| Skånes University Hospital Lund | Lund | Sweden |
| Akademiska Sjukhuset | Uppsala | Sweden |
| Universitaetsspital Basel - Zentrum fur Hamato-Onkologie | Basel | Switzerland |
| Universitaetsspital Bern, Inselspital | Bern | Switzerland |
| Centre Hospitalier Universitaire Vaudois (CHUV)Département d'oncologie | Lausanne | Switzerland |
| Universitaetsspital Zuerich -Universitaeren Herzzentrum Zuerich | Zurich | Switzerland |
| Queen Elizabeth Medical Centre | Birmingham | United Kingdom |
| University Hospital of Wales | Cardiff | United Kingdom |
| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C556306 | daratumumab |
| D000069286 | Bortezomib |
| D000077269 | Lenalidomide |
| D003907 | Dexamethasone |
| D003520 | Cyclophosphamide |
| C024352 | fludarabine |
| ID | Term |
|---|---|
| D001897 | Boronic Acids |
| D000148 | Acids, Noncarboxylic |
| D000143 | Acids |
| D007287 | Inorganic Chemicals |
| D001896 | Boron Compounds |
| D009930 | Organic Chemicals |
| D011719 | Pyrazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D010797 | Phthalimides |
| D010795 | Phthalic Acids |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D010881 | Piperidones |
| D010880 | Piperidines |
| D054833 | Isoindoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
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