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
Cilta-cel: Cilta-cel infusion will be administered at a target dose of 0.75 \* 10\^6 CAR-positive viable T cells/kilogram (kg).
Pomalidomide: Pomalidomide 4 mg will be administered orally.
Bortezomib: Bortezomib 1.3 milligram per meter square (mg/m\^2) will be administered subcutaneously (SC).
Dexamethasone: Dexamethasone 20 mg/day (10mg/day for participants \>75 years of age) (on bortezomib treatment days and the days following bortezomib treatment) will be administered orally in PVd treatment; and orally or intravenous (IV) at 40 mg weekly (20mg weekly for participants \>75 years of age) in DPd treatment.
Daratumumab: Daratumumab 1800 mg will be administered SC.
Study 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
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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 outcome measure(s)
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.
Trial sites (88)
Facility
City
Region
Status
University of Alabama at Birmingham
Birmingham
Alabama
Mayo Clinic Cancer Center-Scottsdale
Phoenix
Arizona
Stanford University Medical Center
Stanford
California
Colorado Blood Cancer Institute
Denver
Colorado
Yale New Haven Hospital
New Haven
Connecticut
University Of Miami Leonard M Mille School Of Medicine SCCC
Miami
Florida
University of Iowa Hospitals and Clinics
Iowa City
Iowa
University of Kansas
Westwood
Kansas
University Of Maryland Medical Center
Baltimore
Maryland
Mayo Clinic - Rochester
Rochester
Minnesota
Washington University School Of Medicine
St Louis
Missouri
Hackensack University Medical Center
Hackensack
New Jersey
Memorial Sloan-Kettering Cancer Center
New York
New York
University of Rochester Medical Center
Rochester
New York
Duke University Medical Center
Durham
North Carolina
The Ohio State University
Columbus
Ohio
Huntsman Cancer Institute
Salt Lake City
Utah
Wisconsin Institutes for Medical Research
Madison
Wisconsin
Medical College Of Wisconsin
Milwaukee
Wisconsin
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
Ghent
Belgium
UZ Leuven
Leuven
Belgium
Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart Tilman
Liège
Belgium
Rigshospitalet
Copenhagen
Denmark
CHRU de Lille Hopital Claude Huriez
Lille
France
Hospices Civils de Lyon HCL
Lyon
France
CHU de Montpellier Hopital Saint Eloi
Montpellier
France
C.H.U. Hotel Dieu - France
Nantes
France
Hopital Saint Louis
Paris
France
CHU De Poitiers
Poitiers
France
Institut Universitaire du cancer de Toulouse-Oncopole
Toulouse
France
Universitaetsklinikum Koeln
Cologne
Germany
Universitatsklinikum Carl Gustvav Carus Dresden an der Technischen Universitat Dresden
Dresden
Germany
Universitaetsklinikum Hamburg Eppendorf
Hamburg
Germany
+ 48 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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