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A Study to Evaluate the Safety of bb2121 in Subjects With High Risk, Newly Diagnosed Multiple Myeloma (NDMM) (KarMMa-4) (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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04196491
Recruitment Status : Recruiting
First Posted : December 12, 2019
Last Update Posted : February 18, 2020
Sponsor:
Information provided by (Responsible Party):
Celgene

Tracking Information
First Submitted Date  ICMJE December 10, 2019
First Posted Date  ICMJE December 12, 2019
Last Update Posted Date February 18, 2020
Estimated Study Start Date  ICMJE February 20, 2020
Estimated Primary Completion Date December 3, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 10, 2019)
  • Dose-limiting toxicity (DLT) rates [ Time Frame: Up to approximately 2 years after first 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: Up to approximately 5 years after first 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 10, 2019)
  • Proportion of subjects who achieved Complete Response (CR) Rate [ Time Frame: Approximately 2.5 years after first 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 2.5 years after first 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 2.5 years after first 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 2.5 years after first 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 2.5 years after first subject bb2121 infused ]
    Is defined as time to start lenalidomide maintenance therapy post-bb2121 infusion
  • Feasibility of initiating maintenance [ Time Frame: Approximately 2.5 years after first subject bb2121 infused ]
    Number of subjects starting the maintenance or on maintenance between D90 and D110
  • Progression-free Survival (PFS) [ Time Frame: Approximately 2.5 years after first 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 2.5 years after first subject bb2121 infused ]
    Is defined as time from bb2121 infusion date to time of death due to any cause
  • Pharmacokinetics - Cmax [ Time Frame: Approximately 2.5 years after first subject bb2121 infused ]
    Maximum transgene level
  • Pharmacokinetics - Tmax [ Time Frame: Approximately 2.5 years after first subject bb2121 infused ]
    Time to peak transgene level
  • Pharmacokinetics - AUC [ Time Frame: Approximately 2.5 years after first subject bb2121 infused ]
    Area under the curve of the transgene level
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Safety of bb2121 in Subjects With High Risk, Newly Diagnosed Multiple Myeloma (NDMM) (KarMMa-4)
Official Title  ICMJE A Phase 1, Open-label, Multicenter Study to Evaluate the Safety of bb2121 in Subjects With High Risk, Newly Diagnosed Multiple Myeloma (KarMMa-4)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Biological: bb2121 carfilzomib
    CAR-T Cell Therapy
    Other Name: ide-cel
  • Drug: Fludarabine
    Lymphodepleting Chemotherapy
  • Drug: Cyclophosphamide
    Lymphodepleting Chemotherapy
  • Drug: Lenalidomide
    Maintenance Therapy
Study Arms  ICMJE Experimental: Dose Escalation
  • bb2121 autologous CAR T cells will be infused at a dose ranging from 150 - 800 x 10^6 CAR+ T cells after receiving lymphodepleting chemotherapy with a planned starting dose of 450 x 10^6 CAR+ T cells.
  • Lenalidomide maintenance therapy is recommended for all patients and should be initiated upon adequate bone marrow recovery or from 90-day post-bb2121 infusion, whichever is later
Interventions:
  • Biological: bb2121 carfilzomib
  • Drug: Fludarabine
  • Drug: Cyclophosphamide
  • Drug: Lenalidomide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 10, 2019)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 9, 2024
Estimated Primary Completion Date December 3, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Subjects must satisfy all of the following criteria to be enrolled in the study:

  1. Subject is newly diagnosed and has symptomatic Multiple Myeloma (MM) prior to initiating induction anti-myeloma therapy
  2. Subject is ≥ 18 years of age at the time of initial diagnosis of MM
  3. Subject has measurable disease at initial diagnosis by

    • M-protein and/or
    • Light chain MM without measurable disease in the serum or urine
  4. 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
  5. Subject has Eastern Cooperative Oncology Group performance ≤ 1
  6. 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:

  1. Subject has non-secretory MM

    During Screening:

  2. Subject received any treatments for MM other than up to 3 cycles of induction therapy per protocol
  3. Subject has any of the following laboratory abnormalities:

    1. Absolute neutrophil count < 1,000/μL
    2. Platelet count < 50,000 mm3
    3. Hemoglobin < 8 g/dL (< 4.9 mmol/L)
    4. Serum creatinine clearance < 45 mL/min
    5. Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L)
    6. Serum aspartate aminotransferase or alanine aminotransferase > 2.5 × upper limit of normal
    7. Serum total bilirubin > 1.5 × ULN or > 3.0 mg/dL for subjects with documented Gilbert's syndrome
    8. INR or aPTT > 1.5 × ULN
  4. Subject has history or presence of clinically significant CNS pathology
  5. Subjects has high risk for developing deep vein thrombosis or pulmonary embolus and are unable or unwilling to undergo anti-thrombotic therapy
  6. Subject has peripheral neuropathy of > Grade 2 severity according to the NCI CTCAE Version 4.03 with bortezomib based induction regimen
  7. Subjects has moderate or severe pulmonary hypertension
  8. Subject has intolerance to components of induction regimen (KRd or RVd) or has any contraindication to one or the other drug
  9. Subject has not recovered from induction therapy-related toxicities (non-hematologic) to < grade 1 CTCAE at the time of screening
  10. Subject has prior history of deep vein thrombosis or pulmonary embolus (PE) within 6 months of starting study treatment
  11. Subject has cardiac conditions such as:

    1. Echocardiogram or multi gated acquisition assessment of left ventricular ejection fraction < 45%
    2. Subject has a history of clinically significant cardiovascular disease or clinically significant ECG abnormalities
  12. Subject has Pulmonary conditions such as:

    1. Subject has known chronic obstructive pulmonary with a forced expiratory vol in 1 sec 50% of predicted normal.
    2. Inadequate pulmonary function defined as oxygen saturation < 92 % on room air
  13. Subject needs ongoing treatment with chronic immunosuppressants
  14. Subject has history of primary immunodeficiency
  15. Subject is seropositive for human immunodeficiency virus, chronic or active hepatitis B or active hepatitis A or C
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04196491
Other Study ID Numbers  ICMJE BB2121-MM-004
U1111-1243-5088 ( Other Identifier: WHO )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: 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/
Responsible Party Celgene
Study Sponsor  ICMJE Celgene
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Uma Arunagiri, MD Celgene/BMS
PRS Account Celgene
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP