A Study of CC-98633, BCMA-targeted Chimeric Antigen Receptor (CAR) T Cells, in Participants With Relapsed and/or Refractory Multiple Myeloma

A Phase I, Multi Center, Open Label Study of CC-98633, BCMA Targeted NEX-T Chimeric Antigen Receptor (CAR) T Cells, in Subjects With Relapsed and/or Refractory Multiple Myeloma

This is a Phase 1, multicenter, open-label study of CC-98633, BCMA-Targeted NEX-T Chimeric Antigen Receptor (CAR) T Cells, in participants with relapsed and/or refractory multiple myeloma.

The study will consist of 2 parts: dose-escalation (Part A) and dose-expansion (Part B). The dose-escalation part (Part A) of the study is to evaluate the safety and tolerability of increasing dose levels of CC-98633 to establish a recommended Phase 2 dose RP2D(s); and the dose-expansion part (Part B) of the study is to further evaluate the safety, pharmacokinetics/pharmacodynamics, and efficacy of CC-98633 at the RP2D(s).

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Biological: CC-98633

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Local Institution - 103
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Local Institution - 111
  • California
    • Stanford, California, United States, 94305
      • Local Institution - 110
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Local Institution - 107
  • Kansas
    • Westwood, Kansas, United States, 66205-2003
      • Local Institution - 101
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Local Institution - 109
  • New York
    • Buffalo, New York, United States, 14263
      • Local Institution - 106
    • New York, New York, United States, 10029
      • Local Institution - 104
    • New York, New York, United States, 10065
      • Local Institution - 102
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Local Institution - 108
  • Texas
    • Dallas, Texas, United States, 75390
      • Local Institution - 105

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years.
2. Signed written informed consent prior to any study procedure.

3. Relapsed and/or refractory multiple myeloma (MM).

   1. Subjects must have documented progressive disease as per International Myeloma Working Group (IMWG) criteria during or within 12 months of completing treatment with the last anti-myeloma treatment regimen before study entry. Also, subjects with confirmed progressive disease within 6 months prior to start of Screening and who are refractory (or non-responsive) to their most recent anti-myeloma treatment regimen afterwards will be also eligible.
   2. Part A and Part B Cohort A: Subjects must have confirmed at least 3 prior antimyeloma treatment regimens.
   3. Part B Cohort B only: Subjects must have received at least 1 but no greater than 3 prior antimyeloma treatment regimens, including a proteasome inhibitor and immunomodulatory agent.
   4. Subjects must have previously received all of the following therapies:

   i) Autologous stem cell transplant ii) A regimen that included an immunomodulatory agent (eg, thalidomide, lenalidomide, pomalidomide) and a proteasome inhibitor (eg, bortezomib, carfilzomib, ixazomib), either alone or combination iii) Anti-CD38 (eg, daratumumab), either alone or combination Subjects in Cohort B do not require prior anti-CD38 antibody therapy.

4. Measurable disease
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
6. Adequate organ function

Exclusion Criteria:

1. Known active or history of central nervous system (CNS) involvement of MM
2. Active or history of plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) syndrome, or clinically significant amyloidosis
3. Prior treatment with CAR T-cell or another genetically modified T-cell therapy
4. Part A and Part B Cohort A only: Prior treatment with investigational therapy directed at BCMA
5. Uncontrolled or active infection
6. Active autoimmune disease requiring immunosuppressive therapy
7. History or presence of clinically significant CNS pathology such as seizure disorder, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: CC-98633; Subjects will receive CC-98633 following 3 consecutive doses of lymphodepleting chemotherapy (fludarabine and cyclophosphamide).

Biological: CC-98633; Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) to produce CC-98633. During CC-98633 production, subjects may receive bridging chemotherapy for disease control. Upon successful generation of CC-98633 product, subjects will receive treatment with CC-98633 therapy. Study treatment will include lymphodepleting chemotherapy followed by one dose of CC-98633 administered by intravenous (IV) injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AEs)	incidence and severity of AEs. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE.	From the time of informed consent and follow up to 2 years after infusion of CC-98633:

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	The proportion of subjects with a partial response (PR) or better by the IMWG criteria.	Up to 2 years after CC-98633 infusion
Complete Response (CR) Rate	The proportion of subjects achieving stringent CR or CR.	Up to 2 years after CC-99633 infusion
Duration of response (DOR)	The time from first response (sCR, CR, VGPR, or PR) to progressive disease (PD) or death.	Up to 2 years after CC-98633 infusion
Time to response (TTR)	Time from CC-98633 infusion to the first documentation of response (sCR, CR, VGPR or PR).	Up to 2 years after CC-98633 infusion
Time to complete response (TTCR)	Time from CC-98633 infusion to the first documentation of sCR or CR	Up to 2 years after CC-98633 infusion
Progression free survival (PFS)	Time from CC-98633 infusion to the first documentation of PD, or death from any cause, whichever occurs first	Up to 2 years after CC-98633 infusion
Overall survival (OS)	Time from CC-98633 infusion to death	Up to 2 years after CC-98633 infusion
Pharmacokinetics - maximum serum concentration (Cmax)	Maximum blood concentration	Up to 2 years after CC-98633 infusion
Pharmacokinetics -time to peak serum concentration (tmax)	Time to peak (maximum) blood concentration	Up to 2 years after CC-98633 infusion
Pharmacokinetics - Area under curve (AUC)	Area under the curve	Up to 2 years after CC-98633 infusion
Very good partial response (VGPR) or better	Is define as proportion of subjects achieving sCR, CR, or VGPR	Up to 2 years after CC-98633 infusion

Collaborators and Investigators

• Sponsor: Juno Therapeutics, a Subsidiary of Celgene
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• FDA Safety Alerts and Recalls
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2020
• Primary Completion (Actual): July 3, 2024
• Study Completion (Actual): July 3, 2024

Study Registration Dates

• First Submitted: May 14, 2020
• First Submitted That Met QC Criteria: May 14, 2020
• First Posted (Actual): May 19, 2020

Study Record Updates

• Last Update Posted (Actual): July 26, 2024
• Last Update Submitted That Met QC Criteria: July 24, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Multiple Myeloma; CAR-T; Myeloma; BCMA; CART; BCMA CAR-T; Myeloma Multiple; CC-98633; BCMA CART
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: CC-98633-MM-001; U1111-1251-3435 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Information relating to our policy on data sharing and the process for requesting data can be found at the following link:

https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

• IPD Sharing Time Frame: See Plan Description
• IPD Sharing Access Criteria: See Plan Description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No