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JOURNAL ONKOLOGIE – STUDIE
KarMMa-2

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

Rekrutierend

NCT-Nummer:
NCT03601078

Studienbeginn:
Dezember 2018

Letztes Update:
09.02.2024

Wirkstoff:
bb2121, Lenalomide, Talquetamab

Indikation (Clinical Trials):
Multiple Myeloma, Neoplasms, Plasma Cell

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Celgene

Collaborator:
-

Studienleiter

Bristol-Myers Squibb
Study Director
Bristol-Myers Squibb

Kontakt

BMS Study Connect Contact Center www.BMSStudyConnect.com
Kontakt:
Phone: 855-907-3286
E-Mail: Clinical.Trials@bms.com» Kontaktdaten anzeigen
First line of the email MUST contain the NCT# and Site #.

Studienlocations
(3 von 26)

Local Institution - 506
20246 Hamburg
(Hamburg)
GermanyAbgeschlossen» Google-Maps
Local Institution - 0802
02118 Boston
United StatesZurückgezogen» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

Anti-myeloma bridging treatment is allowed for disease control while bb2121 is being

manufactured for cohorts 1, 2a and 2b only.

Ein-/Ausschlusskriterien

Inclusion Criteria:

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

1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF)

2. For Cohorts 1 and 2 only, participant has measurable disease, defined as:

- M-protein (serum protein electrophoresis [sPEP] or urine protein electrophoresis

[uPEP]): sPEP ≥ 0.5 g/dL or uPEP ≥ 200 mg/24 hours and/or

- Light chain MM without measurable disease in the serum or urine: Serum

immunoglobulin free light chain ≥ 10 mg/dL and abnormal serum immunoglobulin

kappa lambda free light chain ratio

3. Subjects with one of the following cohort specific requirements:

Cohort 1 RRMM subjects with ≥ 3 prior anti-myeloma treatment regimens:

- Subject must have received at least 3 prior anti-myeloma treatment regimens.

Note: induction with or without hematopoietic stem cell transplant and with or

without maintenance therapy is considered a single regimen

- Subject must have undergone at least 2 consecutive cycles of treatment for each

regimen, unless PD was the best response to the regimen

- Subject must have received prior treatment with a proteasome inhibitor, an

immunomodulatory agent and an anti-CD38 antibody

- Subject has evidence of PD on or within 60 days of the most recent prior

treatment regimen

- Subject achieved a response (minimal response [MR] or better) to at least 1 prior

treatment regimen

Cohort 2 subjects with 1 prior anti-myeloma treatment regimen:

- Subject must have received only 1 prior anti-myeloma treatment regimen. Note:

induction with or without hematopoietic stem cell transplant and with or without

maintenance therapy is considered a single regimen

- Subject must have the following HR factors:

- Early relapse defined as:

Cohort 2a: PD < 18 months since date of start of initial therapy. Initial therapy must

contain induction, ASCT (single or tandem) and lenalidomide containing maintenance.

Cohort 2b: PD < 18 months since date of start or initial therapy which must contain at

minimum, a proteasome inhibitor, an immunomodulatory agent and dexamethasone Cohort

2c: Subject must have received minimum 3 cycles of induction therapy which must

contain at minimum, a proteasome inhibitor, an immunomodulatory agent and

dexamethasone. Subjects must have had ASCT (single or tandem AND < VGPR (excluding PD)

at first assessment between 70 to 110 days after last ASCT, with initial therapy

without consolidation and maintenance.

Cohort 3 participants with newly diagnosed MM (NDMM) who received only induction and

ASCT, without subsequent consolidation or maintenance Cohort 3

- Must have received 4 to 6 cycles of induction therapy which must contain at

minimum, a proteasome inhibitor and an immunomodulatory agent and must have had

single ASCT within 6 months prior to consent

- Must have achieved documented PR or VGPR at first post-ASCT assessment

approximately 100 days after ASCT and this response must be maintained at

screening

- Per Investigator's assessment, subject must be a candidate for single-agent

lenalidomide maintenance

4. Subject must have Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

5. Subject must have recovery to Grade 1 or baseline of any non-hematologic toxicities

due to prior treatments, excluding alopecia and Grade 2 neuropathy

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

1. Subject used any investigational agents within 14 days prior to leukapheresis or, for

Cohort 3, within 14 days prior to consent

2. Subject received any of the following within the last 14 days prior to leukapheresis

or, for Cohort 3, within 14 days prior to consent:

1. Plasmapheresis

2. Major surgery (as defined by the investigator)

3. Radiation therapy other than local therapy for myeloma associated bone lesions

4. Use of any systemic anti-myeloma drug therapy

3. Subject with known central nervous system involvement with myeloma

4. Subject has clinical evidence of pulmonary leukostasis and disseminated intravascular

coagulation

5. History or presence of clinically relevant central nervous system (CNS) pathology

6. Subject with active or history of plasma cell leukemia, Waldenstrom's

macroglobulinemia, POEMS syndrome, or clinically significant amyloidosis

7. Inadequate organ function Subject with a history of Class III or IV congestive heart

failure (CHF) or severe nonischemic cardiomyopathy, unstable or poorly controlled

angina, myocardial infarction, or ventricular arrhythmia within the previous 6 months

prior to starting study treatment

8. Ongoing treatment with chronic immunosuppressants

9. Previous history of an allogeneic hematopoietic stem cell transplantation or treatment

with any gene therapy-based therapeutic for cancer or investigational cellular therapy

for cancer or BCMA targeted therapy

10. Subject has received ASCT within 12 weeks prior to leukapheresis

11. Subject has history of primary immunodeficiency

12. Subject is positive for human immunodeficiency virus (HIV-1), chronic or active

hepatitis B or active hepatitis A or C

13. Subject has uncontrolled systemic fungal, bacterial, viral or other infection

(including tuberculosis) despite appropriate antibiotics or other treatment

14. Subject with prior history of malignancies, other than MM, unless the subject has been

free of the disease for ≥ 5 years

15. Pregnant or lactating women

16. Subject with known hypersensitivity to any component of bb2121 product,

cyclophosphamide, fludarabine, and/or tocilizumab

17. Prior history of deep venous thrombosis (DVT) or pulmonary embolus (PE) within 6

months prior to consent (For Cohort 3)

18. For Cohort 1b, previous treatment with any G Protein-Coupled Receptor Class C Group 5

Member D (GPRC5D) targeted therapy or T-cell engagers

19. For Cohort 1b, known allergies, hypersensitivity, or intolerance to talquetamab or its

excipients

Studien-Rationale

Primary outcome:

1. Overall response rate (ORR)- Cohort 1 (Time Frame - Up to approximately 5 years):
Percentage of subjects who achieved partial response (PR) or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by the investigator

2. Complete response (CR) rate - Cohort 1b, 2a, 2b, 2c, and Cohort 3 (Time Frame - Up to approximately 5 years):
Percentage of subjects who achieved CR or stringent CR according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by the investigator

Secondary outcome:

1. Complete response (CR) rate - Cohort 1 (Time Frame - Up to approximately 5 years):
Percentage of subjects who achieved CR or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by the investigator

2. Overall response rate (ORR) - Cohort 1b, 2a, b, c and Cohort 3 (Time Frame - Up to approximately 5 years):
Percentage of subjects who achieved partial response (PR) or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by the investigator

3. Very good partial response (VGPR) rate - Cohort 2c (Time Frame - Up to approximately 5 years):
Percentage of subjects who achieved VGPR or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by the investigator

4. Time to response (TTR) (Time Frame - Up to approximately 5 years):
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]

5. Duration of response (DoR) (Time Frame - Up to approximately 5 years):
Time from first documentation of response (PR or greater) to first documentation of progressive disease (PD) or death from any cause, whichever occurs first

6. Progression-free survival (PFS) (Time Frame - Up to approximately 5 years):
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)

7. Time to progression (TTP) (Time Frame - Up to approximately 5 years):
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)

8. Overall survival (OS) (Time Frame - Up to approximately 5 years):
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)

9. Adverse Events (AEs) (Time Frame - Up to approximately 5 years):
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.

10. Percentage of participants who received lenalidomide maintenance for the first 3 cycles following bb2121 infusion with at least 75% dose compliance - Cohort 3 (Time Frame - Up to 3 months)

11. Pharmacokinetics - Cmax (Time Frame - Minimum 5 years after bb2121 infusion):
Maximum expansion of bb2121 chimeric antigen receptor (CAR) T cells

12. Pharmacokinetics - tmax (Time Frame - Minimum 5 years after bb2121 infusion):
Time to peak of bb2121 CAR T cells

13. Pharmacokinetics - AUC (Time Frame - Minimum 5 years after bb2121 infusion):
Area under the curve of CAR T cells

14. Pharmacokinetics - tlast (Time Frame - Minimum 5 years after bb2121 infusion):
Time to last measurable CAR T cells

15. Pharmacokinetics - AUC0-28days (Time Frame - Minimum 5 years after bb2121 infusion):
Area under the curve of CAR T cells from time zero to Day 28

16. Immunogenicity (Time Frame - Minimum of 2 years after bb2121 infusion):
Development of an anti-CAR antibody response

17. Subject-reported outcomes as measured by European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire (EORTC-QLQ-C30) (Time Frame - Minimum 5 years after bb2121 infusion):
Questionnaire will be used as a measure of health-related quality of life

18. Subject-reported outcomes as measured by EuroQoL Group EQ-5D-5L Health Questionnaire (Time Frame - Minimum 5 years after bb2121 infusion):
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

19. Subject-reported outcomes as measured by EORTC-QLQ-MY20 (Time Frame - Minimum 5 years after bb2121 infusion):
Is a 20-item myeloma module intended for use among patients varying in disease stage and treatment modality

Studien-Arme

  • Experimental: Cohort 1: BB2121 in relapsed and refractory multiple myeloma participants
    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
  • Experimental: Cohort 1b: BB2121 with talquetamab in relapsed and refractory multiple myeloma participants
  • Experimental: Cohort 2a: BB2121 in multiple myeloma with Autologous stem cell transplantation participants
  • Experimental: Cohort 2b: BB2121 in multiple myeloma without Autologous stem cell transplantation participants
  • Experimental: Cohort 2c: BB2121 in multiple myeloma participants with inadequate response post ASCT
  • Experimental: Cohort 3: BB2121 with lenalidomide maintenance in newly diagnosed multiple myeloma

Geprüfte Regime

  • bb2121 (BMS-986395):
    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)
  • Lenalomide (Revlimid®):
    Specified dose on specified days
  • Talquetamab (TALVEY):
    Specified dose on specified days

Quelle: ClinicalTrials.gov


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