BGB-11417-105 - A Phase 1b/2 Dose-Escalation and Cohort-Expansion Study to Determine the Safety and Efficacy of BGB-11417 as Monotherapy, in Combination With Dexamethasone,Dexamethasone/Carfilzomib, Dexamethasone/Daratumumab, and Dexamethasone/Pomalidomide in Patients With Relapsed/Refractory Multiple Myeloma and t(11;14).

Studio Clinico

Patologia: Mieloma

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: No

Fase di studio: 1, I B, II

Linee di trattamento: Seconda linea, Terza/N linea

Criteri di inclusione: 

1- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
2- A confirmed diagnosis of multiple myeloma (must have an M-component in serum and/or urine)
3- Measurable disease defined as:
  - i. M-spike ≥ 500mg/dL, or ii. Urine protein M-spike of ≥ 200 mg/day, or iii. Serum free light chains ≥ 10 mg/dL, and an abnormal κ:λ ratio
4- Participant has documented relapsed or progressive MM on or after any regimen or who are refractory to the most recent line of therapy.
  - i. Relapsed MM is defined as previously treated MM that progresses and requires initiation of salvage therapy but does not meet the criteria for refractory MM.
  - ii. Refractory MM is defined as disease that is nonresponsive (failure to achieve minimal response or development of progressive disease) while on primary or salvage therapy or progresses within 60 days of last therapy.
    1. Participants in Part 1 should have failed all other available options including having had ≥ 3 prior lines of therapy including a proteasome inhibitor, IMiD agent, and an anti-CD38 monoclonal antibody.
    2.Participants in Part 2 should have had and failed ≥ 1 but ≤ 7 prior lines of therapy and will have had prior treatment with both a proteasome inhibitor and an IMiD agent.
Note: A line of therapy consists of greater ≥ 1 complete cycle of a single agent, a regimen consisting of combination of several drugs, or a planned sequential therapy of various regimens. Induction therapy with consolidation and maintenance following stem cell transplant is considered a single line of therapy.
    3. Prior treatment with carfilzomib is allowed but the patient must not be considered carfilzomib refractory and not have had carfilzomib within the past 6 months
5- Positivity for t(11;14) by validated fluorescence in situ hybridization (FISH) testing assay in a pre-defined laboratory
  a. fresh bone marrow aspirate sample must be collected at screening and sent to central laboratory for t(11;14) FISH testing.
6- Adequate organ function defined as:
    1. Hemoglobin ≥ 8.0 g/dL, within 7 days before first dose of study treatment, independent of growth factor support and transfusions
    2. Platelet count ≥ 75,000/μL, within 7 days before first dose of study treatment, independent of growth factor support and transfusions
    3. Absolute neutrophil count (ANC) ≥ 1000/mm3 [ANC = (% of segmented neutrophils + % of segmented bands) x total WBC count within 7 days before first dose of study treatment
    4. ALT and AST ≤ 3 x upper limit of normal (ULN) and total bilirubin ≤ 2.0 x ULN Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 45 mL/min/1.73 m2 calculated by the MDRD-6 formula.

Criteri di esclusione: 

1- Participant has any of the following conditions:
    1. Non secretory MM (Serum free light chains < 10 mg/dL)
    2. Solitary plasmacytoma
    3. Active plasma cell leukemia (ie, either 20% of peripheral white blood cells or > 2.0 x 109/L circulating plasma cells by standard differential)
    4. Waldenström macroglobulinemia
    5. Amyloidosis.
    6. Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS) syndrome
    7. Uncontrolled diabetes (HbA1c > 7% or 53 mmol/mol or requiring insulin at study entry
    8. Chronic respiratory disease that requires continuous oxygen
2- Significant cardiovascular disease, including but not limited to:
    1. Myocardial infarction ≤ 6 months before screening
    2. Ejection fraction ≤ 50%
    3. Unstable angina≤ 3 months before screening
    4. New York Heart Association Class III or IV congestive heart failure
    5. History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
    6. Heart rate-corrected QT interval > 480 milliseconds based on Fridericia's formula
    7. History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place
    8. Uncontrolled hypertension at screening, defined as systolic blood pressure > 170 mmHg and diastolic blood pressure > 105 mmHg by ≥ 2 consecutive measurements
3- Known infection with human immunodeficiency virus (HIV)
4- Serologic status reflecting active viral hepatitis B (HBV) or viral hepatitis C (HCV) infection as follows:
    1. Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Participants with presence of HBcAb, but absence of HBsAg, are eligible if HBV DNA is undetectable (limitation of sensitivity < 20 IU/mL) ,), and if they are willing to undergo monthly monitoring for HBV reactivation.
    2. Presence of HCV antibody. Participants with presence of HCV antibody are eligible if HCV RNA is undetectable (limitation of sensitivity < 15 IU/mL).

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trattamento sperimentale: 

BGB-11417 (Sonrotoclax) in monotherapy or combiation with

Dexamethasone alone, or Dexamethasone/ Carfilzomib

Dexamethasone/ Daratumumab

Dexamethasone/ Pomalidomide

Trattamento di controllo: 

NA

Note generali: 

N.B. Linee di trattamento:
Part. 1: da 4° linea
Part.2 da 2° a 7° linea.

Centri partecipanti

Nord Italia

Centro Italia

Sud Italia e isole

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2023-507751-30-00

Data di inserimento: 22.01.2025

Promotore

BeiGene

Principal Investigator ITALIA

Riferimento: Dr. Info non applicabile

Telefono: 00000

Email: na@na.it

Localita: na