A Phase 1b/2 Study of BGB-11417in Monotherapy and in Various Combinations With Dexamethasone and Carfilzomib in Multiple Myeloma

Study Purpose

Study consists of two parts, a part 1 dose escalation and a part 2 cohort expansion in combination with dexamethasone and carfilzomib intravenously across two cohorts with a monotherapy component as well.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04973605
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1/Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

BeiGene
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries Australia, New Zealand, United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Relapsed/Refractory Multiple Myeloma
Arms & Interventions

Arms

Experimental: Part 1 Dose Escalation

Dose-escalation and de-escalation to determine maximum tolerated dose (MTD)

Experimental: Part 2 Cohort Expansion

There will be 5 expansion cohorts to further evaluate the safety and efficacy of BGB-11417

Interventions

Drug: - BGB-11417

Administered orally daily

Drug: - Dexamethasone

Once weekly either orally or intravenously

Drug: - Carfilzomib

Administered intravenously weekly

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

University of Miami Health System, Miami, Florida

Status

Recruiting

Address

University of Miami Health System

Miami, Florida, 33136

Froedtert Hospital, Milwaukee, Wisconsin

Status

Recruiting

Address

Froedtert Hospital

Milwaukee, Wisconsin, 53226

International Sites

The Alfred Hospital, Melbourne, Victoria, Australia

Status

Recruiting

Address

The Alfred Hospital

Melbourne, Victoria, 3181

Monash Health, Melbourne, Victoria, Australia

Status

Recruiting

Address

Monash Health

Melbourne, Victoria,

St. Vincent's Hospital Melbourne, Fitzroy, Australia

Status

Recruiting

Address

St. Vincent's Hospital Melbourne

Fitzroy, , 3065

Middlemore Hospital, Auckland, New Zealand

Status

Recruiting

Address

Middlemore Hospital

Auckland, ,