Clinical trial NCT04181827: 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
Official title: A Phase 3 Randomized Study Comparing JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against BCMA, Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in Subjects With Relapsed and Lenalidomide-Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Multiple Myeloma
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2019-12-02
Enrollment: 419
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

* 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
* Have received 1 to 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD)
* 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
* 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
* 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):

  1. Hemoglobin \>=8 gram per deciliter (g/dL) (without prior RBC transfusion within 7 days before the laboratory test; recombinant human erythropoietin use is permitted);
  2. 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);
  3. 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;
  4. Lymphocyte count \>=0.3 \* 10\^9/L;
  5. Aspartate aminotransferase (AST) less than or equal to (\<=)3 \* upper limit of normal (ULN);
  6. Alanine aminotransferase (ALT) \<=3 \* ULN;
  7. 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);
  8. 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)

Exclusion Criteria:

* 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

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: From randomization (Day 1) to either progressive disease or death, whichever occurred first (up to 3.9 years)
Secondary outcomes:
measure: Percentage of Participants Who Achieved Complete Response (CR) or Stringent Complete Response (sCR)
timeFrame: From randomization (Day 1) up to 7 years
measure: Percentage of Participants Who Achieved Overall Minimal Residual Disease (MRD) Negative Status (at 10^-5)
timeFrame: From randomization (Day 1) up to 7 years
measure: Percentage of Participants Who Were in CR or sCR and Achieved MRD-negative Status at 12 Months +/-3 Months
timeFrame: From randomization (Day 1) up to 12 months +/- 3 months
measure: Percentage of Participants Who Achieved Sustained MRD-negative Status
timeFrame: From randomization (Day 1) up to 7 years
measure: Overall Survival (OS)
timeFrame: From randomization (Day 1) up to 7 years
measure: Time to Worsening of Symptoms Using the Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q) Total Symptom Score
timeFrame: From randomization (Day 1) up to 7 years
measure: Overall Response Rate (ORR)
timeFrame: From randomization (Day 1) up to 7 years
measure: Progression Free Survival on Next-line Therapy (PFS2)
timeFrame: From randomization (Day 1) up to 7 years
measure: Number of Participants With Treatment-emergent Adverse Events (AEs)
timeFrame: From Cycle 1 Day 1 up to 7 years
measure: Number of Participants With Treatment-emergent Adverse Events (AEs) by Severity
timeFrame: From Cycle 1 Day 1 up to 7 years
measure: Change From Baseline in Systemic Cytokine Concentrations on Participants Who Received Cilta-cel as Study Treatment (Arm B)
timeFrame: From baseline (Cycle 1 Day 1) up to 7 years
measure: Change From Baseline in Levels of CAR-T Cell Activation Markers on Participants Who Received Cilta-cel as Study Treatment (Arm B)
timeFrame: From baseline (Cycle 1 Day 1) up to 7 years (each cycle of 28 days)
measure: 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)
timeFrame: From baseline (Cycle 1 Day 1) up to 7 years (each cycle of 28 days)
measure: Number of Participants With Anti-JNJ-68284528 Antibodies on Participants Who Received Cilta-cel as Study Treatment (Arm B)
timeFrame: From Cycle 1 Day 1 up to 7 years
measure: 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
timeFrame: From baseline (Cycle 1 Day 1) up to 7 years (each cycle of 28 days)
measure: Change From Baseline in Health-Related Quality of Life as Assessed by MySIm-Q Scale Sore
timeFrame: From baseline (Cycle 1 Day 1) up to 7 years (each cycle of 28 days)
measure: 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
timeFrame: From baseline (Cycle 1 Day 1) up to 7 years (each cycle of 28 days)
measure: Change From Baseline in Health-Related Quality of Life as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score
timeFrame: From baseline (Cycle 1 Day 1) up to 7 years (each cycle of 28 days)
measure: 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
timeFrame: From randomization (Day 1) up to 7 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Mayo Clinic Cancer Center-Scottsdale
state: Arizona
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Miami
country: United States
facility: University Of Miami Leonard M Mille School Of Medicine SCCC
state: Florida
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Westwood
country: United States
facility: University of Kansas
state: Kansas
city: Baltimore
country: United States
facility: University Of Maryland Medical Center
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School Of Medicine
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Madison
country: United States
facility: Wisconsin Institutes for Medical Research
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College Of Wisconsin
state: Wisconsin
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
city: Herston
country: Australia
facility: Royal Brisbane and Womens Hospital
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
city: Melbourne
country: Australia
facility: Alfred Health
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
city: Antwerp
country: Belgium
facility: Universitair Ziekenhuis - Antwerpen
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liege
country: Belgium
facility: Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart Tilman
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: LILLE Cedex
country: France
facility: CHRU de Lille Hopital Claude Huriez
city: Montpellier
country: France
facility: CHU de Montpellier Hopital Saint Eloi
city: Nantes
country: France
facility: C.H.U. Hotel Dieu - France
city: Paris cedex 10
country: France
facility: Hopital Saint Louis
city: Pierre Benite cedex
country: France
facility: Centre hospitalier Lyon-Sud
city: Poitiers
country: France
facility: CHU De Poitiers
city: Toulouse cedex 9
country: France
facility: Institut Universitaire du cancer de Toulouse-Oncopole
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustvav Carus Dresden an der Technischen Universitat Dresden
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg Eppendorf
city: Koeln
country: Germany
facility: Universitaetsklinikum Koeln
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig
city: Tubingen
country: Germany
facility: Klinikum der Eberhard Karls Universitaet Abt fur innere Med II Haematologie Onkologie Germany
city: Wuerzburg
country: Germany
facility: Universitatsklinikum Wurzburg
city: Athens
country: Greece
facility: Attikon University General Hospital of Attica
city: Jerusalem
country: Israel
facility: Hadassah University Hospita Ein Kerem
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
city: Bologna
country: Italy
facility: Azienda Opedaliero-Universitaria Policlinico Sant'orsola Malpighi di Bologna
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele HSR
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
city: Turin
country: Italy
facility: A.O.U. Citta della Salute e della Scienza di Torino - Presidio Molinette
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Kanazawa
country: Japan
facility: Kanazawa University Hospital
city: Kyoto
country: Japan
facility: University Hospital Kyoto Prefectural University of Medicine
city: Nagoya
country: Japan
facility: Nagoya City University Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
city: Sendai
country: Japan
facility: Tohoku University Hospital
city: Shibuya
country: Japan
facility: Japanese Red Cross Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul St Marys Hospital
city: Amsterdam
country: Netherlands
facility: VU Medisch Centrum
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Gliwice
country: Poland
facility: Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut BadawczyOddz w Gliwicach
city: Poznan
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Poznaniu
city: Warszawa
country: Poland
facility: Instytut Hematologii i Transfuzjologii
city: Badalona
country: Spain
facility: Inst. Cat. D'Oncologia-Badalona
city: Barcelona
country: Spain
facility: Hosp Clinic de Barcelona
city: Madrid
country: Spain
facility: Hosp. Gral. Univ. Gregorio Maranon
city: Madrid
country: Spain
facility: Hosp. Univ. 12 de Octubre
city: Pamplona
country: Spain
facility: Clinica Univ. de Navarra
city: Salamanca
country: Spain
facility: Hosp Clinico Univ de Salamanca
city: Sevilla
country: Spain
facility: Hosp. Virgen Del Rocio
city: Lund
country: Sweden
facility: Skane University Hospital
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset Huddinge, Hematologiska Kliniken, Huddinge
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
city: Cardiff
country: United Kingdom
facility: University Hospital Wales
city: London
country: United Kingdom
facility: University College Hospital
city: London
country: United Kingdom
facility: Kings College Hospital
city: Manchester
country: United Kingdom
facility: Christie Hospital
city: Newcastle Upon Tyne
country: United Kingdom
facility: Freeman Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: