A Study 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 Participants With Newly Diagnosed Multiple Myeloma (CARTITUDE-6)

• ClinicalTrials.gov Identifier: NCT05257083
• Recruitment Status: Not yet recruiting
• First Posted: February 25, 2022
• Last Update Posted: March 14, 2023
• Sponsor: European Myeloma Network
• Collaborator: Janssen Research & Development, LLC
• Information provided by (Responsible Party): European Myeloma Network

Tracking Information

• First Submitted Date: February 16, 2022
• First Posted Date: February 25, 2022
• Last Update Posted Date: March 14, 2023
• Estimated Study Start Date: August 2023
• Estimated Primary Completion Date: June 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 16, 2022)

• Progression free survival (PFS) [ Time Frame: up to 10 years ( or 300 PFS events) ]
  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
• Sustained MRD-negative CR [ Time Frame: up to 24 months ]
  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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 16, 2022)

• Overall Response (OR) [ Time Frame: up to 17 years ]
  OR is defined as participants who achieve a partial response (PR) or better according to the IMWG criteria.
• Complete Response (CR) or better status [ Time Frame: up to 17 years ]
  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.
• Overall Minimal Residual Disease (MRD) -negative CR [ Time Frame: up to 17 years ]
  achieving MRD-negative CR, as determined by NGS at any time after the date of randomization before initiation of subsequent antimyeloma therapy.
• Time to subsequent antimyeloma therapy [ Time Frame: up to 17 years ]
  Time to subsequent anti-myeloma therapy is defined as the time from randomization to the start of subsequent anti-myeloma therapy.
• Progression Free Survival on Next-line Therapy (PFS2) [ Time Frame: up to 17 years ]
  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.
• Overall Survival (OS) [ Time Frame: up to 17 years ]
  Overall survival is measured from the date of randomization to the date of the participant's death.
• 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 [ Time Frame: up to 17 years ]
  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.
• Change from Baseline in Health-Related Quality of Life as Assessed by MySIm-Q Scale Score [ Time Frame: up to 17 years ]
  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.
• 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 [ Time Frame: up to 17 years ]
  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).
• Change from Baseline in Health-Related Quality of Life as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score [ Time Frame: up to 17 years ]
  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).
• Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) [ Time Frame: up to 280 days ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study 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 Participants With Newly Diagnosed Multiple Myeloma
• Official Title: A Phase 3 Randomized Study Comparing 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 Participants With Newly Diagnosed Multiple Myeloma Who Are Transplant Eligible
• Brief Summary: 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.

Detailed Description

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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Multiple Myeloma

Intervention

• Drug: Daratumumab
  Daratumumab will be administered SC.
• Drug: Bortezomib
  Bortezomib will be administered SC.
• Drug: Lenalidomide
  Lenalidomide will be administered orally.
• Drug: Dexamethasone
  Dexamethasone will be administered orally.
• Drug: Cilta-cel
  Cilta-cel will be administered intravenously
  Other Name: JNJ-68284528
• Drug: Cyclophosphamide
  Cyclophosphamide will be administered intravenously.
• Drug: Fludarabine
  Fludarabine will be administered intravenously.

Study Arms

• Active Comparator: Arm A: DVRd + ASCT+DVRd (Standard Therapy)

  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

  Interventions:

  • Drug: Daratumumab
  • Drug: Bortezomib
  • Drug: Lenalidomide
  • Drug: Dexamethasone
• Experimental: Arm B: DVRd followed by Ciltacabtagene Autoleucel

  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

  Interventions:

  • Drug: Daratumumab
  • Drug: Bortezomib
  • Drug: Lenalidomide
  • Drug: Dexamethasone
  • Drug: Cilta-cel
  • Drug: Cyclophosphamide
  • Drug: Fludarabine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: February 16, 2022): 750
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 2041
• Estimated Primary Completion Date: June 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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:

  1. Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or
  2. Light chain MM without measurable disease in serum or urine: serum Ig free-light chain (FLC) ≥10 mg/dL and abnormal serum Ig kappa lambda FLC ratio.
• ECOG performance status of grade 0 or 1
• Clinical laboratory values within prespecified range.

Exclusion Criteria:

• Prior treatment with CAR-T therapy directed at any target.
• Any prior BCMA target therapy.
• Any prior therapy for MM or smoldering myeloma other than a short course of corticosteroids
• Received a strong cytochrome P450 (CYP)3A4 inducer within 5 half-lives prior to randomization
• Received or plans to receive any live, attenuated vaccine (except for COVID-19 vaccines) within 4 weeks prior to randomization.
• Known active, or prior history of central nervous system (CNS) involvement or clinical signs of meningeal involvement of MM
• Stroke or seizure within 6 months of signing Informed Consent Form (ICF)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Sarah Lonergan; +31 107033123; sarah.lonergan@emn.life

• Listed Location Countries: Australia, Belgium, Czechia, Germany, Greece, Israel, Italy, Korea, Republic of, Netherlands, Spain, Switzerland

Administrative Information

• NCT Number: NCT05257083
• Other Study ID Numbers: EMN28/68284528MMY3005; 2021-003284-10 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.

• Current Responsible Party: European Myeloma Network
• Original Responsible Party: Same as current
• Current Study Sponsor: European Myeloma Network
• Original Study Sponsor: Same as current
• Collaborators: Janssen Research & Development, LLC
• Investigators: Not Provided
• PRS Account: European Myeloma Network
• Verification Date: March 2023