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

Primary Purpose

Multiple Myeloma

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CC-98633
Sponsored by
Juno Therapeutics, a Subsidiary of Celgene
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple Myeloma, Myeloma, Myeloma Multiple, CC-98633, BCMA, CAR-T, CART, BCMA CART, BCMA CAR-T

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Local Institution - 103
  • Local Institution - 111
  • Local Institution - 110
  • Local Institution - 107
  • The University of Kansas Cancer Center - Westwood
  • Local Institution - 109
  • Local Institution - 106
  • Local Institution - 104
  • Local Institution - 102
  • Local Institution - 108
  • Local Institution - 105

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CC-98633

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
May 14, 2020
Last Updated
February 28, 2023
Sponsor
Juno Therapeutics, a Subsidiary of Celgene
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1. Study Identification

Unique Protocol Identification Number
NCT04394650
Brief Title
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

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 18, 2020 (Actual)
Primary Completion Date
June 23, 2025 (Anticipated)
Study Completion Date
June 23, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Juno Therapeutics, a Subsidiary of Celgene

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Multiple Myeloma, Myeloma, Myeloma Multiple, CC-98633, BCMA, CAR-T, CART, BCMA CART, BCMA CAR-T

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CC-98633
Arm Type
Experimental
Arm Description
Subjects will receive CC-98633 following 3 consecutive doses of lymphodepleting chemotherapy (fludarabine and cyclophosphamide).
Intervention Type
Biological
Intervention Name(s)
CC-98633
Intervention Description
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.
Primary Outcome Measure Information:
Title
Adverse Events (AEs)
Description
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.
Time Frame
From the time of informed consent and follow up to 2 years after infusion of CC-98633:
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
The proportion of subjects with a partial response (PR) or better by the IMWG criteria.
Time Frame
Up to 2 years after CC-98633 infusion
Title
Complete Response (CR) Rate
Description
The proportion of subjects achieving stringent CR or CR.
Time Frame
Up to 2 years after CC-99633 infusion
Title
Duration of response (DOR)
Description
The time from first response (sCR, CR, VGPR, or PR) to progressive disease (PD) or death.
Time Frame
Up to 2 years after CC-98633 infusion
Title
Time to response (TTR)
Description
Time from CC-98633 infusion to the first documentation of response (sCR, CR, VGPR or PR).
Time Frame
Up to 2 years after CC-98633 infusion
Title
Time to complete response (TTCR)
Description
Time from CC-98633 infusion to the first documentation of sCR or CR
Time Frame
Up to 2 years after CC-98633 infusion
Title
Progression free survival (PFS)
Description
Time from CC-98633 infusion to the first documentation of PD, or death from any cause, whichever occurs first
Time Frame
Up to 2 years after CC-98633 infusion
Title
Overall survival (OS)
Description
Time from CC-98633 infusion to death
Time Frame
Up to 2 years after CC-98633 infusion
Title
Pharmacokinetics - maximum serum concentration (Cmax)
Description
Maximum blood concentration
Time Frame
Up to 2 years after CC-98633 infusion
Title
Pharmacokinetics -time to peak serum concentration (tmax)
Description
Time to peak (maximum) blood concentration
Time Frame
Up to 2 years after CC-98633 infusion
Title
Pharmacokinetics - Area under curve (AUC)
Description
Area under the curve
Time Frame
Up to 2 years after CC-98633 infusion
Title
Very good partial response (VGPR) or better
Description
Is define as proportion of subjects achieving sCR, CR, or VGPR
Time Frame
Up to 2 years after CC-98633 infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 18 years. Signed written informed consent prior to any study procedure. Relapsed and/or refractory multiple myeloma (MM). 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. Part A and Part B Cohort A: Subjects must have confirmed at least 3 prior antimyeloma treatment regimens. 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. 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. Measurable disease Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Adequate organ function Exclusion Criteria: Known active or history of central nervous system (CNS) involvement of MM Active or history of plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) syndrome, or clinically significant amyloidosis Prior treatment with CAR T-cell or another genetically modified T-cell therapy Part A and Part B Cohort A only: Prior treatment with investigational therapy directed at BCMA Uncontrolled or active infection Active autoimmune disease requiring immunosuppressive therapy 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Local Institution - 103
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Local Institution - 111
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
Local Institution - 110
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Local Institution - 107
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
The University of Kansas Cancer Center - Westwood
City
Westwood
State/Province
Kansas
ZIP/Postal Code
66205-2003
Country
United States
Facility Name
Local Institution - 109
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Local Institution - 106
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
Local Institution - 104
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Local Institution - 102
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Local Institution - 108
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Local Institution - 105
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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 URL
https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/
Links:
URL
https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
Description
BMS Clinical Trial Information
URL
https://www.bmsstudyconnect.com/s/US/English/USenHome
Description
BMS Clinical Trial Patient Recruiting
URL
https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm
Description
FDA Safety Alerts and Recalls

Learn more about this trial

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

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