Active, not recruiting
Phase 3
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
Condition(s) studied
Multiple Myeloma
Investigational drug(s) / intervention(s)
Cilta-celPomalidomideBortezomibDexamethasoneDaratumumab
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
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.