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

Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04394650
• Other study ID #: CC-98633-MM-001
• Secondary ID: U1111-1251-3435
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: August 18, 2020
• Est. completion date: June 23, 2025

Study information

• Verified date: February 2023
• Source: Juno Therapeutics, a Subsidiary of Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 150
• Est. completion date: June 23, 2025
• Est. primary completion date: June 23, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

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.

Locations

Country	Name	City	State
United States	Local Institution - 103	Birmingham	Alabama
United States	Local Institution - 106	Buffalo	New York
United States	Local Institution - 108	Charlotte	North Carolina
United States	Local Institution - 107	Chicago	Illinois
United States	Local Institution - 105	Dallas	Texas
United States	Local Institution - 102	New York	New York
United States	Local Institution - 104	New York	New York
United States	Local Institution - 111	Phoenix	Arizona
United States	Local Institution - 109	Rochester	Minnesota
United States	Local Institution - 110	Stanford	California
United States	The University of Kansas Cancer Center - Westwood	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Juno Therapeutics, a Subsidiary of Celgene

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Complete Response (CR) Rate	The proportion of subjects achieving stringent CR or CR.	Up to 2 years after CC-99633 infusion
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Overall survival (OS)	Time from CC-98633 infusion to death	Up to 2 years after CC-98633 infusion
Secondary	Pharmacokinetics - maximum serum concentration (Cmax)	Maximum blood concentration	Up to 2 years after CC-98633 infusion
Secondary	Pharmacokinetics -time to peak serum concentration (tmax)	Time to peak (maximum) blood concentration	Up to 2 years after CC-98633 infusion
Secondary	Pharmacokinetics - Area under curve (AUC)	Area under the curve	Up to 2 years after CC-98633 infusion
Secondary	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

External Links

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