A Phase 1b Trial of Teclistamab in Combination With Iberdomide for Relapsed/Refractory Multiple Myeloma

Status: Recruiting
Location: See all (9) locations...
Intervention Type: Procedure, Drug
Study Type: Interventional
Study Phase: Phase 1
SUMMARY

This phase Ib trial tests the safety, side effects, and best dose of iberdomide in combination with teclistamab in treating multiple myeloma that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). Iberdomide is a medication that belongs to a group of drugs known as cereblon E3 ligase modulators. Iberdomide works by targeting and destroying proteins that help myeloma cancer cells to survive. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as teclistamab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Giving iberdomide in combination with teclistamab may be safe and tolerable in treating patients with relapsed or refractory multiple myeloma.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Patients must have histologically or cytologically confirmed multiple myeloma (MM), as defined in the International Myeloma Working Group (IMWG) criteria

• If patients have undergone autologous stem cell transplant (SCT), day 0 of SCT must be \> 100 days to be eligible for the study

• Patients must have had disease progression after ≥ 4 prior lines of anti-myeloma treatments including one proteasome inhibitor (e.g., bortezomib, carfilzomib, ixazomib), one immunomodulatory imide drug (ImiD) (e.g., thalidomide, lenalidomide, pomalidomide \[POM\]), and one anti-CD38 monoclonal antibody (e.g., daratumumab, isatuximab)

• Patients must have measurable disease, defined as:

‣ Serum M-protein ≥ 0.5 g/dL (≥ 5 g/L)

⁃ Urine M-protein ≥ 200 mg/24 h

⁃ Serum free light chain (FLC) assay: involved FLC level ≥ 10 mg/dL (≥ 100 mg/L) and an abnormal serum free light chain ratio (\< 0.26 or \> 1.65)

⁃ Note: Patients with non-secretory disease will be allowed to participate

• Age ≥ 18 years

‣ Because no dosing or adverse event data are currently available on the use of iberdomide in combination with teclistamab in patients \< 18 years of age, children are excluded from this study

• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60)

• Hemoglobin ≥ 7.0 g/dL (≤ 28 days prior to registration) (Without growth factor support, blood transfusion, or platelet stimulating agents for the past 7 days, excluding erythropoietin)

• Absolute neutrophil count ≥ 1,000/mcL (≤ 28 days prior to registration) (Without growth factor support, blood transfusion, or platelet stimulating agents for the past 7 days, excluding erythropoietin)

• Platelets ≥ 50,000/mcL (≤ 28 days prior to registration) (Without growth factor support, blood transfusion, or platelet stimulating agents for the past 7 days, excluding erythropoietin)

• Total bilirubin ≤ 2 x institutional upper limit of normal (ULN) (≤ 28 days prior to registration)

• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x institutional ULN (≤ 28 days prior to registration)

• Estimated glomerular filtration rate (eGFR) \> 30 mL/min (≤ 28 days prior to registration)

• Spot urine (albumin/creatine ratio) ≤ 500mg/g (56 mg/mmol) OR urine dipstick negative/trace (if \> 1+ only eligible if confirmed ≤ 500 mg/g (56 mg/mmol) by albumin/creatinine ratio (spot urine from first void) (≤ 28 days prior to registration)

• Note: Laboratory results obtained during screening should be used to determine eligibility criteria. In situations where laboratory results are outside the permitted range, the investigator may re-test the subject and the subsequent within range screening result may be used to confirm eligibility

• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated

• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

• Patients with treated brain metastases are eligible if follow-up brain imaging done a minimum of 28 days after completion of central nervous system (CNS)-directed therapy shows no evidence of progression

• Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy

• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better

• Based on the mechanism of action, teclistamab may cause fetal harm when administered to a pregnant woman. Females of child-bearing potential (FCBP): should use effective contraception during treatment with teclistamab and for 5 months after the last dose. FCBP should not breast feed during treatment with teclistamab and for 5 months after the last dose. Should a FCBP become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. The effects of iberdomide on the developing human fetus are unknown. However, IMiDs are known to be teratogenic. FCBP must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days prior to starting iberdomide, and again within 24 hours. FCBP must either commit to continued abstinence from heterosexual intercourse or begin two acceptable methods of birth control-one highly effective method and one additional effective method-at the same time, at least 28 days before starting iberdomide, while taking iberdomide, and for 28 days following discontinuation from the study. Examples of highly effective methods are intrauterine device, hormonal contraceptives, tubal ligation, or partner's vasectomy. Examples of barrier method are male condom, diaphragm, or cervical cap. FCBP must also agree to ongoing pregnancy testing. Men must practice complete abstinence or agree to use a condom during sexual contact with FCBP while participating in the study, during dose interruptions, and for at least 28 days following discontinuation from the study, even if he has undergone a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risk of fetal exposure

• Men must agree to abstain from donating and semen or sperm while taking iberdomide, during dose interruptions, and for at least 28 days after the last dose of iberdomide. FCBP must agree not to donate eggs (ova, oocytes) for the purpose of reproduction during this period

• All patients must agree to abstain from donating blood products while taking iberdomide and for at least 28 days after the last dose of iberdomide

• Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study subjects

• Willingness to adhere to the study visit schedule and other protocol requirements and provide mandatory blood and bone marrow specimens for correlative research

• Willingness to return to the enrolling institution for follow-up

Locations
United States
Arizona
Mayo Clinic Hospital in Arizona
RECRUITING
Phoenix
Connecticut
Yale University
RECRUITING
New Haven
Yale-New Haven Hospital North Haven Medical Center
RECRUITING
North Haven
Florida
Mayo Clinic in Florida
RECRUITING
Jacksonville
Moffitt Cancer Center
RECRUITING
Tampa
Minnesota
Mayo Clinic in Rochester
RECRUITING
Rochester
Ohio
Ohio State University Comprehensive Cancer Center
RECRUITING
Columbus
Oklahoma
University of Oklahoma Health Sciences Center
RECRUITING
Oklahoma City
Virginia
VCU Massey Comprehensive Cancer Center
RECRUITING
Richmond
Time Frame
Start Date: 2024-12-06
Estimated Completion Date: 2026-09-16
Participants
Target number of participants: 26
Treatments
Experimental: Treatment (iberdomide, teclistamab)
Patients receive teclistamab SC on days 1, 4, 7, 15 and 22 for cycle 1 and days 1, 8, 15 and 22 for remaining cycles. Patients also receive iberdomide PO QD on days 1-21 for cycle 2 and beyond. Cycles repeat every 28 days for up to 4 years in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood and urine sample collection, bone marrow aspiration and biopsy and PET/CT or PET/MR throughout the trial.
Sponsors
Leads: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov