Trial record 1 of 1 for:
NCT04196491
A Study to Evaluate the Safety of bb2121 in Subjects With High Risk, Newly Diagnosed Multiple Myeloma (NDMM) (KarMMa-4)
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| ClinicalTrials.gov Identifier: NCT04196491 |
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Recruitment Status :
Active, not recruiting
First Posted : December 12, 2019
Last Update Posted : October 10, 2022
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Sponsor:
Celgene
Information provided by (Responsible Party):
Celgene
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Brief Summary:
This is a multicenter, open-label, phase 1, single arm study intended to determine the optimal target dose and safety of bb2121 in subjects with HR (R-ISS Stage III per IMWG criteria) NDMM. Subjects should have received 3 Cycles of standard induction therapy prior to undergoing leukapheresis procedure to collect autologous mononuclear cells for manufacture of the drug product (bb2121). Following manufacture of the drug product, subjects will receive fourth cycle of induction therapy followed by lymphodepleting therapy with fludarabine and cyclophosphamide prior to bb2121 infusion. Maintenance therapy is recommended for all subjects who have received bb2121 infusion and should be initiated upon adequate bone marrow recovery or from 90-day post-bb2121 infusion, whichever is later.
| 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 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Multiple myeloma
MedlinePlus related topics:
Multiple Myeloma
| Arm | Intervention/treatment |
|---|---|
Experimental: Dose Escalation
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Biological: bb2121
CAR-T Cell Therapy
Other Name: ide-cel Drug: Fludarabine Lymphodepleting Chemotherapy Drug: Cyclophosphamide Lymphodepleting Chemotherapy Drug: Lenalidomide Maintenance Therapy |
Primary Outcome Measures :
- 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.
Secondary Outcome Measures :
- 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
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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
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Subject has measurable disease at initial diagnosis by
- M-protein and/or
- Light chain MM without measurable disease in the serum or urine
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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
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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:
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Subject has non-secretory MM
During Screening:
- Subject received any treatments for MM other than up to 3 cycles of induction therapy per protocol
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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
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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
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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
Information from the National Library of Medicine
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
Locations
Show 41 study locations
Sponsors and Collaborators
Celgene
Investigators
| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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 |
Keywords provided by Celgene:
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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 |
Additional relevant MeSH terms:
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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 |