Clinical trial NCT04394650: A Study of CC-98633, BCMA-targeted Chimeric Antigen Receptor (CAR) T Cells, in Participants With Relapsed and/or Refractory Multiple Myeloma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Myeloma
Myeloma Multiple
CC-98633
BCMA
CAR-T
CART
BCMA CART
BCMA CAR-T
Lead sponsor: Juno Therapeutics, a Subsidiary of Celgene
Sponsor class: INDUSTRY
First posted: 2020-05-19
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: 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

Primary outcomes:
measure: Adverse Events (AEs)
timeFrame: From the time of informed consent and follow up to 2 years after infusion of CC-98633:
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to 2 years after CC-98633 infusion
measure: Complete Response (CR) Rate
timeFrame: Up to 2 years after CC-99633 infusion
measure: Duration of response (DOR)
timeFrame: Up to 2 years after CC-98633 infusion
measure: Time to response (TTR)
timeFrame: Up to 2 years after CC-98633 infusion
measure: Time to complete response (TTCR)
timeFrame: Up to 2 years after CC-98633 infusion
measure: Progression free survival (PFS)
timeFrame: Up to 2 years after CC-98633 infusion
measure: Overall survival (OS)
timeFrame: Up to 2 years after CC-98633 infusion
measure: Pharmacokinetics - maximum serum concentration (Cmax)
timeFrame: Up to 2 years after CC-98633 infusion
measure: Pharmacokinetics -time to peak serum concentration (tmax)
timeFrame: Up to 2 years after CC-98633 infusion
measure: Pharmacokinetics - Area under curve (AUC)
timeFrame: Up to 2 years after CC-98633 infusion
measure: Very good partial response (VGPR) or better
timeFrame: Up to 2 years after CC-98633 infusion
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Local Institution - 103
state: Alabama
city: Phoenix
country: United States
facility: Local Institution - 111
state: Arizona
city: Stanford
country: United States
facility: Local Institution - 110
state: California
city: Chicago
country: United States
facility: Local Institution - 107
state: Illinois
city: Westwood
country: United States
facility: Local Institution - 101
state: Kansas
city: Rochester
country: United States
facility: Local Institution - 109
state: Minnesota
city: Buffalo
country: United States
facility: Local Institution - 106
state: New York
city: New York
country: United States
facility: Local Institution - 104
state: New York
city: New York
country: United States
facility: Local Institution - 102
state: New York
city: Charlotte
country: United States
facility: Local Institution - 108
state: North Carolina
city: Dallas
country: United States
facility: Local Institution - 105
state: Texas
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: