A Study Comparing JNJ-68284528, a CAR-T Therapy Directed Against B-cell Maturation Antigen (BCMA), Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in Participants With Relapsed and Lenalidomide-Refractory Multiple Myeloma
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT04181827
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
The purpose of this study is to compare the efficacy of ciltacabtagene autoleucel (cilta-cel) with standard therapy, either Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd).
- Detailed Description
Multiple myeloma is a malignant plasma cell disorder diagnosed annually in approximately 86,000 participants worldwide. JNJ-68284528 (cilta-cel) is an autologous chimeric antigen receptor T-cell (CAR-T) therapy that targets B-cell maturation antigen (BCMA), a molecule expressed on the surface of mature B lymphocytes and malignant plasma cells. The primary hypothesis for this study is that JNJ-68284528 (cilta-cel) will significantly improve progression free survival (PFS) compared with standard therapy (PVd or DPd), in participants who have previously received 1 to 3 prior line(s) of therapy, that included a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) and who are refractory to lenalidomide. This study will be conducted in 3 phases: Screening (up to 28 days before randomization), Treatment, and Follow-Up. Assessment like patient-reported outcome(s) (PROs) assessments, electrocardiogram (ECG), vital signs, pharmacokinetic will be performed during the study. Safety evaluations will include review of adverse events, laboratory test results, vital sign measurements, physical examination findings, and assessments of cardiac function, Immune Effector Cell-associated Encephalopathy (only for Arm B) and Eastern Cooperative Oncology Group performance status. Safety data will be periodically reviewed by an Independent Data Monitoring Committee (IDMC). The duration of the study is approximately 6 years.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 419
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Measurable disease at screening as defined by any of the following: (a) Serum monoclonal paraprotein (M-protein) level greater than or equal to (>=) 0.5 gram per deciliter (g/dL) or urine M-protein level >=200 milligram (mg)/24 hours; or (b) Light chain multiple myeloma without measurable M-protein in the serum or the urine: Serum free light chain >=10 mg/dL and abnormal serum free light chain ratio
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Have received 1 to 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD)
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Have documented evidence of PD by International Myeloma Working Group (IMWG) criteria based on investigator's determination on or within 6 months of their last regimen
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Be refractory to lenalidomide per IMWG consensus guidelines (failure to achieve minimal response or progression on or within 60 days of completing lenalidomide therapy). Progression on or within 60 days of the last dose of lenalidomide given as maintenance will meet this criterion. For participants with more than 1 prior line of therapy, there is no requirement to be lenalidomide refractory to the most recent line of prior therapy. However, participants must be refractory to lenalidomide in at least one prior line
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Have clinical laboratory values meeting the following criteria during the Screening Phase (re testing is allowed but the below criteria must be met in the latest test prior to randomization):
- Hemoglobin >=8 gram per deciliter (g/dL) (without prior RBC transfusion within 7 days before the laboratory test; recombinant human erythropoietin use is permitted);
- Absolute neutrophil count (ANC) >=1 * 10^9 per liter (L) (without recombinant human granulocyte colony-stimulating factor [G-CSF] within 7 days and without pegylated G-CSF within 14 days of the laboratory test);
- Platelet count >=75 * 10^9/L (without prior platelet transfusion within 7 days before the laboratory test) in participants in whom less than (<) 50 percent (%) of bone marrow nucleated cells are plasma cells; platelet count >=50 * 10^9/L (without prior platelet transfusion within 7 days before the laboratory test) in participants in whom >=50% of bone marrow nucleated cells are plasma cells;
- Lymphocyte count >=0.3 * 10^9/L;
- Aspartate aminotransferase (AST) less than or equal to (<=)3 * upper limit of normal (ULN);
- Alanine aminotransferase (ALT) <=3 * ULN;
- Total bilirubin <=2.0 * ULN; except in participants with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin <=1.5 * ULN is required);
- Estimated glomerular filtration rate >=40 milliliter per minute (mL/min) per 1.73 meter square (m^2) (to be calculated using the Modification of Diet in Renal Disease [MDRD] formula)
- Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy directed at any target
- Any previous therapy that is targeted to B-cell maturation antigen (BCMA)
- Ongoing toxicity from previous anticancer therapy that has not resolved to baseline levels or to Grade 1 or less; except for alopecia
- Participants with Grade 1 peripheral neuropathy with pain or Grade 2 or higher peripheral neuropathy will not be permitted to receive pomalidomide, bortezomib, and dexamethasone (PVd) as standard therapy or bridging therapy; however, participants may receive daratumumab, pomalidomide, and dexamethasone (DPd) as standard therapy or bridging therapy
- Received a cumulative dose of corticosteroids equivalent to >=70 mg of prednisone within the 7 days prior to randomization
- Monoclonal antibody treatment within 21 days
- Cytotoxic therapy within 14 days
- Proteasome inhibitor therapy within 14 days
- Immunomodulatory drug (IMiD) therapy within 7 days
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: PVd or DPd (Standard Therapy) Pomalidomide Participants will receive either PVd or DPd as a standard therapy. In PVd treatment, participants will receive oral pomalidomide 4 mg on Days 1 to 14 in each cycle; bortezomib 1.3 mg/meter square (m\^2) SC on Days 1, 4, 8 and 11 (Cycles 1 to 8) and on Days 1 and 8 (Cycle 9 onwards) and oral dexamethasone 20 mg on Days 1, 2, 4, 5, 8, 9, 11 and 12 (Cycles 1 to 8) and Days 1, 2, 8 and 9 (Cycle 9 onwards). Each cycle will consist of 21 days. In DPd treatment, participants will receive daratumumab SC 1800 mg weekly on Days 1, 8, 15, and 22 (Cycles 1 and 2), every 2 weeks on Days 1 and 15 (Cycles 3 to 6) and every 4 weeks on Day 1 (Cycle 7 onwards); oral pomalidomide 4 mg on Days 1 to 21 (Cycle 1 onwards); dexamethasone 40 mg oral or IV weekly on Days 1, 8, 15, and 22 (Cycle 1 onwards). Each cycle will consist of 28 days. Participants will continue to receive PVd or DPd until confirmed PD, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurs earlier. Arm A: PVd or DPd (Standard Therapy) Bortezomib Participants will receive either PVd or DPd as a standard therapy. In PVd treatment, participants will receive oral pomalidomide 4 mg on Days 1 to 14 in each cycle; bortezomib 1.3 mg/meter square (m\^2) SC on Days 1, 4, 8 and 11 (Cycles 1 to 8) and on Days 1 and 8 (Cycle 9 onwards) and oral dexamethasone 20 mg on Days 1, 2, 4, 5, 8, 9, 11 and 12 (Cycles 1 to 8) and Days 1, 2, 8 and 9 (Cycle 9 onwards). Each cycle will consist of 21 days. In DPd treatment, participants will receive daratumumab SC 1800 mg weekly on Days 1, 8, 15, and 22 (Cycles 1 and 2), every 2 weeks on Days 1 and 15 (Cycles 3 to 6) and every 4 weeks on Day 1 (Cycle 7 onwards); oral pomalidomide 4 mg on Days 1 to 21 (Cycle 1 onwards); dexamethasone 40 mg oral or IV weekly on Days 1, 8, 15, and 22 (Cycle 1 onwards). Each cycle will consist of 28 days. Participants will continue to receive PVd or DPd until confirmed PD, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurs earlier. Arm A: PVd or DPd (Standard Therapy) Dexamethasone Participants will receive either PVd or DPd as a standard therapy. In PVd treatment, participants will receive oral pomalidomide 4 mg on Days 1 to 14 in each cycle; bortezomib 1.3 mg/meter square (m\^2) SC on Days 1, 4, 8 and 11 (Cycles 1 to 8) and on Days 1 and 8 (Cycle 9 onwards) and oral dexamethasone 20 mg on Days 1, 2, 4, 5, 8, 9, 11 and 12 (Cycles 1 to 8) and Days 1, 2, 8 and 9 (Cycle 9 onwards). Each cycle will consist of 21 days. In DPd treatment, participants will receive daratumumab SC 1800 mg weekly on Days 1, 8, 15, and 22 (Cycles 1 and 2), every 2 weeks on Days 1 and 15 (Cycles 3 to 6) and every 4 weeks on Day 1 (Cycle 7 onwards); oral pomalidomide 4 mg on Days 1 to 21 (Cycle 1 onwards); dexamethasone 40 mg oral or IV weekly on Days 1, 8, 15, and 22 (Cycle 1 onwards). Each cycle will consist of 28 days. Participants will continue to receive PVd or DPd until confirmed PD, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurs earlier. Arm A: PVd or DPd (Standard Therapy) Daratumumab Participants will receive either PVd or DPd as a standard therapy. In PVd treatment, participants will receive oral pomalidomide 4 mg on Days 1 to 14 in each cycle; bortezomib 1.3 mg/meter square (m\^2) SC on Days 1, 4, 8 and 11 (Cycles 1 to 8) and on Days 1 and 8 (Cycle 9 onwards) and oral dexamethasone 20 mg on Days 1, 2, 4, 5, 8, 9, 11 and 12 (Cycles 1 to 8) and Days 1, 2, 8 and 9 (Cycle 9 onwards). Each cycle will consist of 21 days. In DPd treatment, participants will receive daratumumab SC 1800 mg weekly on Days 1, 8, 15, and 22 (Cycles 1 and 2), every 2 weeks on Days 1 and 15 (Cycles 3 to 6) and every 4 weeks on Day 1 (Cycle 7 onwards); oral pomalidomide 4 mg on Days 1 to 21 (Cycle 1 onwards); dexamethasone 40 mg oral or IV weekly on Days 1, 8, 15, and 22 (Cycle 1 onwards). Each cycle will consist of 28 days. Participants will continue to receive PVd or DPd until confirmed PD, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurs earlier. Arm B: (Ciltacabtagene Autoleucel [Cilta-cel]) Cilta-cel Participants will receive at least one cycle of bridging therapy (PVd or DPd) and additional cycles of bridging therapy may be considered based on participant's clinical status and timing of availability of cilta-cel along with conditioning regimen (cyclophosphamide 300 milligram \[mg\]/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).
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) From randomization (Day 1) to either progressive disease or death, whichever occurred first (up to 3.9 years) PFS: defined as time from date of randomization to date of first documented progressed disease (PD) as per International Myeloma Working Group (IMWG) criteria, or death due to any cause, whichever occurred first. PD: increase of 25% from lowest response value: serum and urine M-component (absolute increase must be \>=0.5 grams per deciliter \[g/dL\] and \>=200 milligrams \[mg\] per 24 hours, respectively); only in participants without measurable serum and urine M-protein levels, difference between involved and uninvolved free light chain (FLC) levels (absolute increase of \>10 mg/dL); only in participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow plasma cell (PC)% (absolute increase of \>=10%), appearance of new lesion; definite development of new bone lesions or definite increase in size of existing bone lesions, \>=50% increase in circulating PCs (minimum of 200 cells per microliter \[uL\]) if this was only measure of disease.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Health-Related Quality of Life as Assessed by European Quality of Life - 5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire Scale Score From baseline (Cycle 1 Day 1) up to 7 years (each cycle of 28 days) Percentage of Participants Who Achieved Sustained MRD-negative Status From randomization (Day 1) up to 7 years Change From Baseline in Systemic Cytokine Concentrations on Participants Who Received Cilta-cel as Study Treatment (Arm B) From baseline (Cycle 1 Day 1) up to 7 years Change From Baseline in Levels of CAR-T Cell Activation Markers on Participants Who Received Cilta-cel as Study Treatment (Arm B) From baseline (Cycle 1 Day 1) up to 7 years (each cycle of 28 days) Number of Participants With Anti-JNJ-68284528 Antibodies on Participants Who Received Cilta-cel as Study Treatment (Arm B) From Cycle 1 Day 1 up to 7 years Change From Baseline in Health-Related Quality of Life as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score From baseline (Cycle 1 Day 1) up to 7 years (each cycle of 28 days) Change From Baseline in Levels of JNJ-68284528 T Cell Expansion (Proliferation), and Persistence on Participants Who Received Cilta-cel as Study Treatment (Arm B) From baseline (Cycle 1 Day 1) up to 7 years (each cycle of 28 days) 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 Item (EORTC-QLQ-C30) Scale Score From baseline (Cycle 1 Day 1) up to 7 years (each cycle of 28 days) Percentage of Participants Who Achieved Complete Response (CR) or Stringent Complete Response (sCR) From randomization (Day 1) up to 7 years Percentage of Participants Who Achieved Overall Minimal Residual Disease (MRD) Negative Status (at 10^-5) From randomization (Day 1) up to 7 years Percentage of Participants Who Were in CR or sCR and Achieved MRD-negative Status at 12 Months +/-3 Months From randomization (Day 1) up to 12 months +/- 3 months Overall Response Rate (ORR) From randomization (Day 1) up to 7 years Number of Participants With Treatment-emergent Adverse Events (AEs) From Cycle 1 Day 1 up to 7 years Overall Survival (OS) From randomization (Day 1) up to 7 years Time to Worsening of Symptoms Using the Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q) Total Symptom Score From randomization (Day 1) up to 7 years Progression Free Survival on Next-line Therapy (PFS2) From randomization (Day 1) up to 7 years Change From Baseline in Health-Related Quality of Life as Assessed by MySIm-Q Scale Sore From baseline (Cycle 1 Day 1) up to 7 years (each cycle of 28 days) Number of Participants With Treatment-emergent Adverse Events (AEs) by Severity From Cycle 1 Day 1 up to 7 years Number of Participants in Health-Related Quality of Life as Assessed by The Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Item From randomization (Day 1) up to 7 years
Trial Locations
- Locations (88)
Kings College Hospital
🇬🇧London, United Kingdom
Christie Hospital
🇬🇧Manchester, United Kingdom
Freeman Hospital
🇬🇧Newcastle Upon Tyne, United Kingdom
Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut BadawczyOddz w Gliwicach
🇵🇱Gliwice, Poland
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Mayo Clinic Cancer Center-Scottsdale
🇺🇸Phoenix, Arizona, United States
Stanford University Medical Center
🇺🇸Stanford, California, United States
Colorado Blood Cancer Institute
🇺🇸Denver, Colorado, United States
Yale New Haven Hospital
🇺🇸New Haven, Connecticut, United States
University Of Miami Leonard M Mille School Of Medicine SCCC
🇺🇸Miami, Florida, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
University of Kansas
🇺🇸Westwood, Kansas, United States
University Of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
Mayo Clinic - Rochester
🇺🇸Rochester, Minnesota, United States
Washington University School Of Medicine
🇺🇸Saint Louis, Missouri, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
The Ohio State University
🇺🇸Columbus, Ohio, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
Wisconsin Institutes for Medical Research
🇺🇸Madison, Wisconsin, United States
Medical College Of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Royal Adelaide Hospital
🇦🇺Adelaide, Australia
Royal Prince Alfred Hospital
🇦🇺Camperdown, Australia
Royal Brisbane and Womens Hospital
🇦🇺Herston, Australia
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Australia
Alfred Health
🇦🇺Melbourne, Australia
Fiona Stanley Hospital
🇦🇺Murdoch, Australia
Universitair Ziekenhuis - Antwerpen
🇧🇪Antwerp, Belgium
UZ Gent
🇧🇪Gent, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart Tilman
🇧🇪Liege, Belgium
Rigshospitalet
🇩🇰Copenhagen, Denmark
CHRU de Lille Hopital Claude Huriez
🇫🇷LILLE Cedex, France
CHU de Montpellier Hopital Saint Eloi
🇫🇷Montpellier, France
C.H.U. Hotel Dieu - France
🇫🇷Nantes, France
Hopital Saint Louis
🇫🇷Paris cedex 10, France
Centre hospitalier Lyon-Sud
🇫🇷Pierre Benite cedex, France
CHU De Poitiers
🇫🇷Poitiers, France
Institut Universitaire du cancer de Toulouse-Oncopole
🇫🇷Toulouse cedex 9, France
Universitatsklinikum Carl Gustvav Carus Dresden an der Technischen Universitat Dresden
🇩🇪Dresden, Germany
Universitaetsklinikum Hamburg Eppendorf
🇩🇪Hamburg, Germany
Universitaetsklinikum Koeln
🇩🇪Koeln, Germany
Universitaetsklinikum Leipzig
🇩🇪Leipzig, Germany
Klinikum der Eberhard Karls Universitaet Abt fur innere Med II Haematologie Onkologie Germany
🇩🇪Tubingen, Germany
Universitatsklinikum Wurzburg
🇩🇪Wuerzburg, Germany
Attikon University General Hospital of Attica
🇬🇷Athens, Greece
Hadassah University Hospita Ein Kerem
🇮🇱Jerusalem, Israel
Sheba Medical Center
🇮🇱Ramat Gan, Israel
Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Azienda Opedaliero-Universitaria Policlinico Sant'orsola Malpighi di Bologna
🇮🇹Bologna, Italy
IRCCS Ospedale San Raffaele HSR
🇮🇹Milano, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, Italy
Policlinico Universitario Agostino Gemelli
🇮🇹Roma, Italy
A.O.U. Citta della Salute e della Scienza di Torino - Presidio Molinette
🇮🇹Turin, Italy
Kyushu University Hospital
🇯🇵Fukuoka, Japan
Kanazawa University Hospital
🇯🇵Kanazawa, Japan
University Hospital Kyoto Prefectural University of Medicine
🇯🇵Kyoto, Japan
Nagoya City University Hospital
🇯🇵Nagoya, Japan
Okayama University Hospital
🇯🇵Okayama, Japan
Hokkaido University Hospital
🇯🇵Sapporo, Japan
Tohoku University Hospital
🇯🇵Sendai, Japan
Japanese Red Cross Medical Center
🇯🇵Shibuya, Japan
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea Seoul St Marys Hospital
🇰🇷Seoul, Korea, Republic of
VU Medisch Centrum
🇳🇱Amsterdam, Netherlands
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Erasmus MC
🇳🇱Rotterdam, Netherlands
UMC Utrecht
🇳🇱Utrecht, Netherlands
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Uniwersytecki Szpital Kliniczny w Poznaniu
🇵🇱Poznan, Poland
Instytut Hematologii i Transfuzjologii
🇵🇱Warszawa, Poland
Inst. Cat. D'Oncologia-Badalona
🇪🇸Badalona, Spain
Hosp Clinic de Barcelona
🇪🇸Barcelona, Spain
Hosp. Gral. Univ. Gregorio Maranon
🇪🇸Madrid, Spain
Hosp. Univ. 12 de Octubre
🇪🇸Madrid, Spain
Clinica Univ. de Navarra
🇪🇸Pamplona, Spain
Hosp Clinico Univ de Salamanca
🇪🇸Salamanca, Spain
Hosp. Virgen Del Rocio
🇪🇸Sevilla, Spain
Skane University Hospital
🇸🇪Lund, Sweden
Karolinska Universitetssjukhuset Huddinge, Hematologiska Kliniken, Huddinge
🇸🇪Stockholm, Sweden
Akademiska Sjukhuset
🇸🇪Uppsala, Sweden
Queen Elizabeth Hospital
🇬🇧Birmingham, United Kingdom
Bristol Haematology and Oncology Centre
🇬🇧Bristol, United Kingdom
University Hospital Wales
🇬🇧Cardiff, United Kingdom
University College Hospital
🇬🇧London, United Kingdom