Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Antineoplastic Agents

All Drugs and Chemicals

Lenalidomide

Idecabtagene vicleucel

Antineoplastic Agents, Immunological

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

bb2121 consists of autologous T lymphocytes transduced with an anti-BCMA CAR lentiviral vector to express a chimeric antigen receptor targeting the human B cell maturation antigen (anti-BCMA CAR)

bb2121

Lenalomide

Talquetamab

BMS Study Connect Contact Center www.BMSStudyConnect.com

First line of the email MUST contain the NCT# and Site #.

Leif Bergsagel, Site 151

Alfred Chung, Site 152

Melissa Alsina, Site 153

Madhav Dhodapkar, Site 149

Noopur Raje, Site 146

Adam Sperling, Site 145

David Avigan, Site 159

Ravi Vij, Site 156

Christopher Dangelo, Site 155

David Siegel, Site 144

Shambavi Richard, Site 154

Ran Reshef, Site 157

Barry Paul, Site 150

Jesus Berdeja, Site 142

Larry Anderson, Site 148

Krina Patel, Site 147

Daniel Egan, Site 143

Meera Mohan, Site 158

Site 404

Site 505

Site 703

Site 704

Site 801

Bristol-Myers Squibb

This study is a multi-cohort, open-label, multicenter Phase 2 study to evaluate the efficacy and safety of bb2121 in participants with relapsed and refractory multiple myeloma (RRMM) (Cohort 1), in participants with RRMM who receive bridging therapy with talquetamab (Cohort 1b), in participants with multiple myeloma (MM) having progressed within 18 months of initial treatment with autologous stem cell transplantation (ASCT) (Cohort 2a) and without ASCT (Cohort 2b) or, in participants with inadequate response post ASCT during initial treatment (Cohort 2c) and the efficacy and safety of bb2121 used in combination with lenalidomide maintenance in participants with suboptimal response post ASCT (Cohort 3). Approximately 264 participants will be enrolled into one of three cohorts. Cohort 1 (including cohort 1b) will enroll approximately 126 RRMM subjects with ≥ 3 prior anti-myeloma treatment regimens. Cohort 2a will enroll approximately 39 MM subjects, with 1 prior anti-myeloma therapy including ASCT and with early relapse. Cohort 2b will enroll approximately 39 MM subjects with 1 prior anti-myeloma therapy not including ASCT and with early relapse. Cohort 2c will enroll approximately 30 MM subjects with inadequate response to ASCT during their initial anti-myeloma therapy. The cohorts will start in parallel and independently. Cohort 3 will enroll approximately 30 newly diagnosed multiple myeloma (NDMM) participants with suboptimal response to ASCT.

Anti-myeloma bridging treatment is allowed for disease control while bb2121 is being manufactured for cohorts 1, 2a and 2b only.

An Efficacy and Safety Study of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma and in Subjects With High-Risk Multiple Myeloma

A Phase 2, Multi-cohort, Open-label, Multicenter Study to Evaluate the Efficacy and Safety of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma and in Subjects With Clinical High-Risk Multiple Myeloma (KarMMa-2)

Percentage of subjects who achieved partial response (PR) or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by the investigator

Percentage of subjects who achieved CR or stringent CR according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by the investigator

Percentage of subjects who achieved CR or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by the investigator

Percentage of subjects who achieved VGPR or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by the investigator

Time from first bb2121 infusion to first documentation of response (PR or greater) \[Cohorts 1 and 2\]; time from first dose of lenalidomide pre-leukapheresis to first documentation of response \[Cohort 3 only\]

Time from first documentation of response (PR or greater) to first documentation of progressive disease (PD) or death from any cause, whichever occurs first

Time from first bb2121 infusion to first documentation of PD, or death due to any cause, whichever occurs first (Cohorts 1 and 2); time from first dose of lenalidomide pre-leukapheresis to first documentation of PD, or death due to any cause, whichever occurs first (Cohort 3 only)

Time from first bb2121 infusion to first documentation of PD (Cohorts 1 and 2); time from first dose of lenalidomide pre-leukapheresis to first documentation of PD (Cohort 3 only)

Time from first bb2121 infusion to time of death due to any cause (Cohorts 1 and 2); time from first dose of lenalidomide pre-leukapheresis to time of death due to any cause (Cohort 3 only)

Type, frequency, seriousness and severity of adverse events (AEs), adverse events of special interest (AESIs) (including cytokine release syndrome, neurotoxicity and infection), and relationship of AE to study drug.

Maximum expansion of bb2121 chimeric antigen receptor (CAR) T cells

Area under the curve of CAR T cells from time zero to Day 28

Development of an anti-CAR antibody response

Questionnaire will be used as a measure of health-related quality of life

Is a standardized measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal

Is a 20-item myeloma module intended for use among patients varying in disease stage and treatment modality

Celgene

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Anti-Infective Agents

Dexamethasone

Bortezomib

Daratumumab

Pomalidomide

Dexamethasone acetate

Elotuzumab

Ixazomib

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

HIV Protease Inhibitors

Protease Inhibitors

Enzyme Inhibitors

The participants will receive one of following regimens dependent on the subject's most recent anti-myeloma treatment regimen:

* Daratumumab (DARA) in combination with pomalidomide (POM) and low-dose dexamethasone (dex) (DPd) OR
* DARA in combination with bortezomib (BTZ) and low-dose dex (DVd) OR
* Ixazomib (IXA) in combination with lenalidomide (LEN) and low-dose dex (IRd) OR
* Carfilzomib (CFZ) in combination with low-dose dexamethasone (Kd) OR
* Elotuzumab (ELO) in combination with POM and low-dose dexamethasone (EPd)

Carfilzomib

This is a multicenter, randomized, open-label, Phase 3 study comparing the efficacy and safety of bb2121 versus standard regimens in subjects with relapsed and refractory multiple myeloma (RRMM).

The study is anticipated to randomize approximately 381 subjects with RRMM. Approximately 254 subjects will be randomized to Treatment Arm A and approximately 127 subjects will be randomized to Treatment Arm B.

Efficacy and Safety Study of bb2121 Versus Standard Regimens in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM)

A Phase 3, Multicenter, Randomized, Open-label Study to Compare the Efficacy and Safety of bb2121 Versus Standard Regimens in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM) (KarMMa-3)

Time from randomization to the first documentation of progressive disease based on the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma assessed by an independent response committee (IRC) or death due to any cause, whichever occurs first.

Time from randomization to time of death due to any cause

Time from randomization to the first documentation of progressive disease, first day when subject receives another anti-myeloma treatment or death due to any cause, whichever occurs first

Percentage of subjects who achieved partial response (PR) or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by an IRC

Percentage of MRD evaluable subjects that are MRD negative (defined at a minimum of 1 in 10\^5 nucleated cells) using flow cytometry (EuroFlow) and next generation sequencing (NGS)

Percentage of subjects who achieved CR or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by an IRC

Time from first documentation of response (PR or better) to first documentation of disease progression or death from any cause, whichever occurs first

TTR is calculated as the time from randomization to the initial documented response (PR or better) based on IMWG guideline for responders

Number of participants with adverse events

Maximum peak in bb2121 chimeric antigen receptor (CAR) T cells

Time from randomization to first day when subject receives another anti-myeloma treatment

Time from randomization to second objective disease progression or death from any cause, whichever is first

Amino Acids

Glycine

Neurotransmitter Agents

Ixazomib as the single drug for maintenance. This group as control arm

Ixazomib combined with low-dose lenalidomide(10mg) for maintenance

Whether Ixazomib combined with low-dose lenalidomide improves the outcome and prognosis of patients with high-risk multiple myeloma as a maintenance treatment option compared to ixazolomib alone

Ixazomib plus low-dose lenalidomide

Yang Xu, MD,PhD

Xuzhao Zhang, MD,PhD

This study was designed to investigate whether the oral proteasome inhibitor ixazomib combined with low-dose lenalidomide(10mg) as a maintenance regimen could improve the outcome and prognosis of patients with high-risk multiple myeloma after induction and consolidation of VRD-based regimen.

Ixazomib Plus Low-dose Lenalidomide Versus Ixazomib Alone for Maintenance Treatment of High Risk Multiple Myeloma

Exploratory Study of Ixazomib in Combination With Reduced Dose Lenalidomide Versus Ixazomib Alone for Maintenance Treatment of High Risk Multiple Myeloma

PFS is defined as the time from the date of first dose of study drug to the first occurrence of PD as evaluated by the investigator or death from any cause, whichever occurs first. PD is defined as \>=25% increase from lowest value in serum M component or urine M-component; difference between involved and uninvolved free light chain (FLC) levels (absolute increase \>10 mg/dL); bone marrow plasma cell percent \>/=10%; new bone lesions or soft tissue plasmacytomas development or definite increase in existing bone lesions/soft tissue plasmacytomas size; hypercalcaemia development.

OS is measured as the time from the date of first dose of study drug to the date of death.

Adverse events are defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 30 days after the last dose of study drug.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
An Efficacy and Safety Study of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma and in Subjects With High-Risk Multiple Myeloma	NCT03601078	Multiple Myelom...	bb2121 Lenalomide Talquetamab	18 Years -	Celgene
Efficacy and Safety Study of bb2121 Versus Standard Regimens in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM)	NCT03651128	Multiple Myelom...	bb2121 Daratumumab Pomalidomide Dexamethasone Bortezomib Ixazomib Lenalidomide Carfilzomib Elotuzumab	18 Years -	Celgene
Ixazomib Plus Low-dose Lenalidomide Versus Ixazomib Alone for Maintenance Treatment of High Risk Multiple Myeloma	NCT05722405	Multiple Myelom...	Ixazomib plus l... Ixazomib	18 Years - 80 Years	Second Affiliated Hospital, School of Medicine, Zhejiang University
Efficacy and Safety Study of bb2121 Versus Standard Regimens in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM)	NCT03651128	Multiple Myelom...	bb2121 Daratumumab Pomalidomide Dexamethasone Bortezomib Ixazomib Lenalidomide Carfilzomib Elotuzumab	18 Years -	Celgene

Spots Global Cancer Trial Database for high risk multiple myeloma