Multiple MyelomaPhase 1NCT02658929
Study of bb2121 in Multiple Myeloma
A Phase 1 study testing bb2121 in people with Multiple Myeloma, run by Celgene at 9 sites in United States.
Trial summary
Study CRB-401 is a 2-part, non-randomized, open label, multi-site Phase 1 study of bb2121 in adults with relapsed/refractory multiple myeloma (MM). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- bb2121
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 67 participants
- Where
- 9 sitesUnited States
- Study dates
- 22 Dec 2015to 22 Sep 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 years of age at the time of signing informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Subjects must have measurable disease including at least one of the criteria below:
- Serum M-protein greater or equal to 0.5 g/dL Urine M-protein greater or equal to 200 mg/24 h Serum free light chain (FLC) assay: involved FLC level greater or equal to 10 mg/dL (100 mg/L) provided serum FLC ratio is abnormal -Women of child-bearing potential (WCBP) must have a negative serum pregnancy test prior to treatment and refrain from tissue donation including egg donation or any other tissue/blood/organ donations, for at least 1 year following bb2121 infusion. All sexually active WCBP and all sexually active male subjects must agree to use effective methods of birth control throughout the study. All sexually active males subjects must refrain from tissue donation including egg donation or any other tissue/blood/organ donations, for at least 1 year following bb2121 infusion.
- Part A:
- Diagnosis of MM with relapsed or refractory disease and have had at least 3 different prior lines of therapy including proteasome inhibitor (e.g., bortezomib or carfilzomib) and immunomodulatory therapy (IMiD; e.g., lenalidomide or pomalidomide), or have "double refractory" disease to a proteasome inhibitor and IMiD, defined as progression on or within 60 days of treatment with these agents
- Part B: Diagnosis of MM with relapsed or refractory disease with previous exposure to PI (e.g., bortezomib or carfilzomib), IMiDs (e.g., lenalidomide or pomalidomide), and daratumumab, and refractory (based on IMWG criteria) to their last line of therapy
Who cannot join
- Subjects with known central nervous system disease
- Inadequate hepatic function
- Inadequate renal function
- Inadequate bone marrow function
- Presence of active infection within 72 hours
- Significant co-morbid condition or disease which in the judgment of the Investigator would place the subject at undue risk or interfere with the study; examples include, but are not limited to, cirrhotic liver disease, sepsis, recent significant traumatic injury, and other conditions
Show all 11Show fewer
- Subjects with second malignancies in addition to myeloma if the second malignancy has required therapy in the last 3 years or is not in complete remission
- Subjects with a history of class III or IV congestive heart failure or non-ischemic cardiomyopathy, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the previous 6 months
- Known human immunodeficiency virus (HIV) positivity
- Subjects who have plasma cell leukemia or clinically significant amyloidosis
- Pregnant or lactating women
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
National Cancer Institute
Bethesda, Maryland, 20892
Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Sarah Cannon Research Inst
Nashville, Tennessee, 37203
Mt. Sinai Medical Center Division of Hematology/Oncology
New York, New York, 10029
Mayo Clinic
Rochester, Minnesota, 55905
Stanford Cancer Center
Stanford, California, 94305
About this study
Official title: CRB-401 A Phase 1 Study of bb2121 in BCMA-Expressing Multiple Myeloma
Study CRB-401 is a 2-part, non-randomized, open label, multi-site Phase 1 study of bb2121 in adults with relapsed/refractory multiple myeloma (MM).
Read the detailed description
This is a 2-part, non-randomized, open label, multi-site Phase 1 study. the study design consists of 2 parts: Part A (Dose Escalation), in which the RP2D is determined, and Part B (Expansion Cohorts), in which subjects are treated with the determined RP2D.
Following consent, enrolled subjects will undergo a leukapheresis procedure to collect autologous mononuclear cells for manufacture of investigational drug product (bb2121). Following manufacture of the drug product, subjects will receive lymphodepleting therapy with fludarabine and cyclophosphamide prior to bb2121 infusion. All subjects who have received bb2121 infusion will be followed for up to 60 months on CRB-401.
All subjects who complete the study, as well as those who withdraw from the study after receiving bb2121 for reasons other than death or meeting the early termination criteria, will be asked to continue to undergo long-term follow-up in a companion study for up to 15 years after their last bb2121 infusion, with a focus on long-term safety and efficacy.
- Conditions
- Multiple Myeloma
- Being tested
- bb2121
- Keywords
- Multiple Myeloma, Efficacy and Safety, bb2121, CAR T Cell, BCMA
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bb2121Biological
bb2121
| Study group | Role | What they receive |
|---|---|---|
| bb2121 | Experimental | bb2121 autologous CAR T cells will be infused at a dose ranging from 150 - 450 x 10^6 CAR+ T cells after receiving lymphodepleting chemotherapy Receives: Biological: bb2121 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events (AEs) and abnormal laboratory test results, including dose limiting toxicities (DLTs)
Measured: Day 1 through Month 60
Secondary outcomes (1)
Disease-specific response criteria including: overall response rate (ORR), complete response (CR), very good partial response (VGPR), and partial response (PR) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for MM.
Percentage of subjects who achieved a CR, VGR, PR according to IMWG Uniform Response Criteria for Multiple Myeloma (MM).
Measured: Day 1 through Month 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2016 (estimated)
- Study start22 Dec 2015
- Primary completion22 Jul 2019
- Study completion22 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by CelgeneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Genetix Biotherapeutics Inc.
- Responsible party
- Sponsor
- Investigators
- Kristen Hege, MD, Study director, Celgene Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02658929
- Sponsor's protocol ID
- CRB-401
- Status last verified
- Jan 2023
- First submitted
- 15 Jan 2016
- Last updated
- 23 Jan 2023
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Raje N, Berdeja J, Lin Y, Siegel D, Jagannath S, Madduri D, Liedtke M, Rosenblatt J, Maus MV, Turka A, Lam LP, Morgan RA, Friedman K, Massaro M, Wang J, Russotti G, Yang Z, Campbell T, Hege K, Petrocca F, Quigley MT, Munshi N, Kochenderfer JN. Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2019 May 2;380(18):1726-1737. doi: 10.1056/NEJMoa1817226.
PubMed 31042825Lin Y, Raje NS, Berdeja JG, Siegel DS, Jagannath S, Madduri D, Liedtke M, Rosenblatt J, Maus MV, Massaro M, Petrocca F, Yeri A, Finney O, Caia A, Yang Z, Martin N, Campbell TB, Rytlewski J, Fuller J, Hege K, Munshi NC, Kochenderfer JN. Idecabtagene vicleucel for relapsed and refractory multiple myeloma: post hoc 18-month follow-up of a phase 1 trial. Nat Med. 2023 Sep;29(9):2286-2294. doi: 10.1038/s41591-023-02496-0. Epub 2023 Aug 17.
PubMed 37592106
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CRB-401 A Phase 1 Study of bb2121 in BCMA-Expressing Multiple Myeloma
- ClinicalTrials.gov ID
- NCT02658929
- Acronym / sponsor ID
- CRB-401
- Conditions
- Multiple Myeloma
- Keywords
- Multiple Myeloma, Efficacy and Safety, bb2121, CAR T Cell, BCMA
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Collaborators
- Genetix Biotherapeutics Inc.
- Study start
- 22 Dec 2015 (actual)
- Primary completion
- 22 Jul 2019 (actual)
- Study completion
- 22 Sep 2022 (actual)
- First posted
- 20 Jan 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study CRB-401 is a 2-part, non-randomized, open label, multi-site Phase 1 study of bb2121 in adults with relapsed/refractory multiple myeloma (MM).
Detailed description
This is a 2-part, non-randomized, open label, multi-site Phase 1 study. the study design consists of 2 parts: Part A (Dose Escalation), in which the RP2D is determined, and Part B (Expansion Cohorts), in which subjects are treated with the determined RP2D.
Following consent, enrolled subjects will undergo a leukapheresis procedure to collect autologous mononuclear cells for manufacture of investigational drug product (bb2121). Following manufacture of the drug product, subjects will receive lymphodepleting therapy with fludarabine and cyclophosphamide prior to bb2121 infusion. All subjects who have received bb2121 infusion will be followed for up to 60 months on CRB-401.
All subjects who complete the study, as well as those who withdraw from the study after receiving bb2121 for reasons other than death or meeting the early termination criteria, will be asked to continue to undergo long-term follow-up in a companion study for up to 15 years after their last bb2121 infusion, with a focus on long-term safety and efficacy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| bb2121 | Experimental | Biological: bb2121bb2121 autologous CAR T cells will be infused at a dose ranging from 150 - 450 x 10^6 CAR+ T cells after receiving lymphodepleting chemotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 18 years of age at the time of signing informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Subjects must have measurable disease including at least one of the criteria below:
- Serum M-protein greater or equal to 0.5 g/dL Urine M-protein greater or equal to 200 mg/24 h Serum free light chain (FLC) assay: involved FLC level greater or equal to 10 mg/dL (100 mg/L) provided serum FLC ratio is abnormal -Women of child-bearing potential (WCBP) must have a negative serum pregnancy test prior to treatment and refrain from tissue donation including egg donation or any other tissue/blood/organ donations, for at least 1 year following bb2121 infusion. All sexually active WCBP and all sexually active male subjects must agree to use effective methods of birth control throughout the study. All sexually active males subjects must refrain from tissue donation including egg donation or any other tissue/blood/organ donations, for at least 1 year following bb2121 infusion.
- Diagnosis of MM with relapsed or refractory disease and have had at least 3 different prior lines of therapy including proteasome inhibitor (e.g., bortezomib or carfilzomib) and immunomodulatory therapy (IMiD; e.g., lenalidomide or pomalidomide), or have "double refractory" disease to a proteasome inhibitor and IMiD, defined as progression on or within 60 days of treatment with these agents
Key exclusion criteria (11 listed)
- Subjects with known central nervous system disease
- Inadequate hepatic function
- Inadequate renal function
- Inadequate bone marrow function
- Presence of active infection within 72 hours
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| bb2121bb2121 | Biological | bb2121 |
Primary outcome
Incidence of adverse events (AEs) and abnormal laboratory test results, including dose limiting toxicities (DLTs)
Time frame: Day 1 through Month 60
1 secondary outcome
Disease-specific response criteria including: overall response rate (ORR), complete response (CR), very good partial response (VGPR), and partial response (PR) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for MM.
Time frame: Day 1 through Month 60
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2023.
- Background: PubMed 31042825Raje N, Berdeja J, Lin Y, Siegel D, Jagannath S, Madduri D, Liedtke M, Rosenblatt J, Maus MV, Turka A, Lam LP, Morgan RA, Friedman K, Massaro M, Wang J, Russotti G, Yang Z, Campbell T, Hege K, Petrocca F, Quigley MT, Munshi N, Kochenderfer JN. Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2019 May 2;380(18):1726-1737. doi: 10.1056/NEJMoa1817226.
- Derived from this study: PubMed 37592106Lin Y, Raje NS, Berdeja JG, Siegel DS, Jagannath S, Madduri D, Liedtke M, Rosenblatt J, Maus MV, Massaro M, Petrocca F, Yeri A, Finney O, Caia A, Yang Z, Martin N, Campbell TB, Rytlewski J, Fuller J, Hege K, Munshi NC, Kochenderfer JN. Idecabtagene vicleucel for relapsed and refractory multiple myeloma: post hoc 18-month follow-up of a phase 1 trial. Nat Med. 2023 Sep;29(9):2286-2294. doi: 10.1038/s41591-023-02496-0. Epub 2023 Aug 17.
- BMS Clinical Trial InformationLink provided by the sponsor.
- BMS Clinical Trial Patient RecruitingLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kristen Hege, MD study director
Celgene Corporation
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing bb2121 in people with Multiple Myeloma, run by Celgene at 9 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events (AEs) and abnormal laboratory test results, including dose limiting toxicities (DLTs) (time frame: Day 1 through Month 60). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02658929, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2023.