A Study to Evaluate the Safety of bb2121 in Subjects With High Risk, Newly Diagnosed Multiple Myeloma (NDMM) (KarMMa-4)
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT04196491 |
Recruitment Status :
Active, not recruiting
First Posted : December 12, 2019
Last Update Posted : October 10, 2022
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Multiple Myeloma | Biological: bb2121 Drug: Fludarabine Drug: Cyclophosphamide Drug: Lenalidomide | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 13 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase 1, Open-label, Multicenter Study to Evaluate the Safety of bb2121 in Subjects With High Risk, Newly Diagnosed Multiple Myeloma (KarMMa-4) |
Actual Study Start Date : | May 27, 2020 |
Estimated Primary Completion Date : | December 14, 2023 |
Estimated Study Completion Date : | December 14, 2023 |

Arm | Intervention/treatment |
---|---|
Experimental: Dose Escalation
|
Biological: bb2121
CAR-T Cell Therapy
Other Name: ide-cel Drug: Fludarabine Lymphodepleting Chemotherapy Drug: Cyclophosphamide Lymphodepleting Chemotherapy Drug: Lenalidomide Maintenance Therapy |
- Dose-limiting toxicity (DLT) rates [ Time Frame: Up to completion of DLT period after last subject bb2121 infused ]DLTs will be assessed during the DLT interval (ie, within 21 days immediately after bb2121 infusion). DLTs are defined as any bb2121 related Grade 3 to 5 toxicity.
- Adverse Events (AEs) [ Time Frame: Approximately 2 years after last subject bb2121 infused ]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.
- Proportion of subjects who achieved Complete Response (CR) Rate [ Time Frame: Approximately 2 years after last subject bb2121 infused ]Is defined as proportion of subjects who achieved CR or better according to IMWG Uniform Response Criteria for Multiple Myeloma for multiple myeloma will be determined by an Investigator assessment.
- Overall Response Rate (ORR) [ Time Frame: Approximately 2 years after last subject bb2121 infused ]Is defined as proportion of subjects who achieved PR or better according to IMWG Uniform Response Criteria for Multiple Myeloma as determined by an Investigator assessment
- Duration of Response (DoR) [ Time Frame: Approximately 2 years after last subject bb2121 infused ]Is defined as time from first documentation of response (PR or better) to first documentation of progressive disease (PD) or death from any cause, whichever occurs first, for responders.
- Time to Complete Response (TCR) [ Time Frame: Approximately 2 years after last subject bb2121 infused ]Is defined as time from bb2121 infusion date to first documentation of CR for responders (Complete Response (CR) or better).
- Time to start maintenance [ Time Frame: Approximately 2 years after last subject bb2121 infused ]Is defined as time to start lenalidomide maintenance therapy post-bb2121 infusion
- Feasibility of initiating maintenance [ Time Frame: Approximately 2 years after last subject bb2121 infused ]Number of subjects starting the maintenance or on maintenance between D90 and D110
- Progression-free Survival (PFS) [ Time Frame: Approximately 2 years after last subject bb2121 infused ]Is defined as time from bb2121 infusion date to first documentation of PD, or death due to any cause, whichever occurs first.
- Overall Survival (OS) [ Time Frame: Approximately 2 years after last subject bb2121 infused ]Is defined as time from bb2121 infusion date to time of death due to any cause
- Pharmacokinetics - Cmax [ Time Frame: Approximately 2 years after last subject bb2121 infused ]Maximum transgene level
- Pharmacokinetics - Tmax [ Time Frame: Approximately 2 years after last subject bb2121 infused ]Time to peak transgene level
- Pharmacokinetics - AUC [ Time Frame: Approximately 2 years after last subject bb2121 infused ]Area under the curve of the transgene level

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Subjects must satisfy all of the following criteria to be enrolled in the study:
- Subject is newly diagnosed and has symptomatic Multiple Myeloma (MM) prior to initiating induction anti-myeloma therapy
- Subject is ≥ 18 years of age at the time of initial diagnosis of MM
-
Subject has measurable disease at initial diagnosis by
- M-protein and/or
- Light chain MM without measurable disease in the serum or urine
-
Subject has high-risk MM at the time of initial diagnosis of MM per R-ISS Stage III as defined by IMWG:
- ISS Stage III and cytogenetic abnormalities with t(4; 14) and/or del(17p); and/or t(14:16) by iFISH; or;
- ISS Stage III and serum LDH > ULN
- Subject has Eastern Cooperative Oncology Group performance ≤ 1
-
Subjects has received ≤ to 3 cycles of the following induction anti-myeloma therapy prior to enrollment:
- Cycle 1: one of the following regimens (RVd, KRd, CyBorD, D-RVd and D-KRd)
- Cycle 2 to Cycle 3: either KRd or RVd (Cycle 3 must be without dexamethasone)
Exclusion Criteria:
The presence of any of the following will exclude a subject from enrollment: The presence of any of the following will exclude a subject from enrollment:
At initial diagnosis, screening and prior to initiation of induction therapy for MM:
-
Subject has non-secretory MM
During Screening:
- Subject received any treatments for MM other than up to 3 cycles of induction therapy per protocol
-
Subject has any of the following laboratory abnormalities:
- Absolute neutrophil count < 1,000/μL
- Platelet count < 50,000 mm3
- Hemoglobin < 8 g/dL (< 4.9 mmol/L)
- Serum creatinine clearance < 45 mL/min
- Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L)
- Serum aspartate aminotransferase or alanine aminotransferase > 2.5 × upper limit of normal
- Serum total bilirubin > 1.5 × ULN or > 3.0 mg/dL for subjects with documented Gilbert's syndrome
- INR or aPTT > 1.5 × ULN
- Subject has history or presence of clinically significant CNS pathology
- Subjects has high risk for developing deep vein thrombosis or pulmonary embolus and are unable or unwilling to undergo anti-thrombotic therapy
- Subject has peripheral neuropathy of > Grade 2 severity according to the NCI CTCAE Version 4.03 with bortezomib based induction regimen
- Subjects has moderate or severe pulmonary hypertension
- Subject has intolerance to components of induction regimen (KRd or RVd) or has any contraindication to one or the other drug
- Subject has not recovered from induction therapy-related toxicities (non-hematologic) to < grade 1 CTCAE at the time of screening
- Subject has prior history of deep vein thrombosis or pulmonary embolus (PE) within 6 months of starting study treatment
-
Subject has cardiac conditions such as:
- Echocardiogram or multi gated acquisition assessment of left ventricular ejection fraction < 45%
- Subject has a history of clinically significant cardiovascular disease or clinically significant ECG abnormalities
-
Subject has Pulmonary conditions such as:
- Subject has known chronic obstructive pulmonary with a forced expiratory vol in 1 sec 50% of predicted normal.
- Inadequate pulmonary function defined as oxygen saturation < 92 % on room air
- Subject needs ongoing treatment with chronic immunosuppressants
- Subject has history of primary immunodeficiency
- Subject is seropositive for human immunodeficiency virus, chronic or active hepatitis B or active hepatitis A or C

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04196491

Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Celgene |
ClinicalTrials.gov Identifier: | NCT04196491 |
Other Study ID Numbers: |
BB2121-MM-004 U1111-1243-5088 ( Other Identifier: WHO ) |
First Posted: | December 12, 2019 Key Record Dates |
Last Update Posted: | October 10, 2022 |
Last Verified: | October 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
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/ |
Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) Clinical Study Report (CSR) Analytic Code |
Time Frame: | See Plan Description |
Access Criteria: | See Plan Description |
URL: | https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/ |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Multiple Myeloma Newly diagnosed multiple myeloma BB2121 KarMMa-4 Phase I NDMM High Risk |
R-ISS III KRd RVd Dara-KRd Dara-RVd CyBorD BCMA |
Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases Cyclophosphamide |
Fludarabine Lenalidomide Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Growth Inhibitors |