Recurrent Multiple MyelomaPhase 1NCT06465316

Testing Teclistamab (TECVAYLI) in Combination With Iberdomide for Relapsed or Refractory Multiple Myeloma

A Phase 1 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Recurrent Multiple Myeloma and Refractory Multiple Myeloma, run by National Cancer Institute (NCI) at 16 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Recurrent Multiple Myeloma, Refractory Multiple Myeloma
What is being tested?: Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy
Type of treatment: Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 26 participants
Where: 16 sitesUnited States
Study dates: 6 Dec 2024to 31 Dec 2026
Phase: Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

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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

Who cannot join

Patients who have active plasma cell leukemia, active amyloid light chain (AL) (primary) amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, myeloma protein, and skin changes), and Waldenstrom macroglobulinemia are ineligible
If a patient develops recurrent/refractory (R/R) disease while receiving the most recent line of therapy, there is no need for a washout period
Patients who have had prior anti-BCMA directed bispecific antibody (BsAb) therapy exposure (prior treatment with anti-BCMA directed antibody drug conjugate, anti-BCMA-directed chimeric antigen receptor [CAR] T cell therapy, and prior non-BCMA-targeting BsAb are permitted)
Patients who have had prior treatment with a cereblon E3 ligase modulator, including mezigdomide, iberdomide, and CFT7455 (all currently in clinical development)
Patients who received plasmapheresis ≤ 7 days prior to registration
Patients who received a prior allogeneic SCT. Autologous SCT is allowed

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Patients who received a live or live-attenuated vaccine ≤ 30 days prior to registration. Patients are allowed to receive a coronavirus disease 2019 (COVID-19) vaccine at any timepoint during protocol treatment
Systemic active infection requiring treatment
Any unresolved toxicity ≥ grade 2 from previous treatment except for alopecia or peripheral neuropathy up to grade 2
Patients who have had any major surgery ≤ 4 weeks prior to registration
Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make this protocol unreasonably hazardous
Patients with evidence of active mucosal or internal bleeding
Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Stable chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if participant otherwise meets entry criteria
Patients with known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to teclistamab or iberdomide, or any of the components of the study treatment
Patients who are taking any anticancer therapy other than hormonal therapy (for prostrate or breast cancer) and palliative radiotherapy (defined as radiation to ≤ 3 sites of active multiple myeloma)
Patients who require immunosuppressive medications including, but not limited to, systemic corticosteroids at doses exceeding 10 mg/day of prednisone or equivalent. Use of immunosuppressive medications for the management of iberdomide-related adverse events (AEs) or in subjects with contrast allergies is acceptable. In addition, use of inhaled, topical, intranasal corticosteroids or local steroid injection (e.g., intra-articular injection) is permitted. Temporary use of corticosteroids for concurrent illnesses (e.g., food allergies, computed tomography [CT] scan contrast hypersensitivity, pneumonia, etc.) are acceptable
Patients who require medications that are strong inhibitors or inducers of CYP3A4/5
Patients who are receiving any other investigational agents
Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
Pregnant women are excluded from this study because iberdomide is a thalidomide analog and thalidomide is a known human teratogen. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with iberdomide, breastfeeding should be discontinued if the mother is treated with iberdomide. These potential risks may also apply to other agents used in this study
Patients who are unable or unwilling to undergo protocol required thromboembolism prophylaxis are excluded

Trial locations and contacts

16 sites in 1 country. Contact the study team or a site near you to ask about taking part.

City, postcode or hospital

Sites recruiting now only

16 sites in 1 country

United States16 sites, 15 recruiting

Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Site Public Contact, 800-293-5066, Jamesline@osumc.edu
Srinivas S. Devarakonda
Recruiting
Smilow Cancer Hospital-Derby Care Center
Derby, Connecticut, 06418
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Elan Gorshein
Recruiting
Smilow Cancer Hospital Care Center - Guilford
Guilford, Connecticut, 06437
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Elan Gorshein
Recruiting
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980
Site Public Contact, 855-776-0015
Ricardo D. Parrondo
Recruiting
University of Kansas Cancer Center
Kansas City, Kansas, 66160
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Jeries Kort
Recruiting
Yale University
New Haven, Connecticut, 06520
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Elan Gorshein
Recruiting
Yale-New Haven Hospital North Haven Medical Center
North Haven, Connecticut, 06473
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Elan Gorshein
Recruiting
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Suspended
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Jeries Kort
Recruiting
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, 66211
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Jeries Kort
Recruiting
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, 85054
Site Public Contact, 855-776-0015
Ricardo D. Parrondo
Recruiting
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298
Site Public Contact, 804-628-6430, CTOclinops@vcu.edu
Hashim Mann
Recruiting
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Site Public Contact, 855-776-0015
Ricardo D. Parrondo
Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
Site Public Contact, 800-679-0775, ClinicalTrials@moffitt.org
Ariel Grajales-Cruz
Recruiting
Smilow Cancer Hospital-Torrington Care Center
Torrington, Connecticut, 06790
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Elan Gorshein
Recruiting
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Jeries Kort
Recruiting

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVE:

Estimate the recommended phase 2 dose (RP2D) of iberdomide in combination with teclistamab.

SECONDARY OBJECTIVES:

To evaluate the safety and toxicity profile of iberdomide in combination with teclistamab.

II. To observe and record antitumor activity.

CORRELATIVE OBJECTIVES:

To evaluate the changes in the tumor immune microenvironment (exhausted T-cell phenotypes, percent T regulatory cells [T regs], T-cell activation) in peripheral blood and bone marrow caused by the addition of iberdomide to teclistamab and how they relate to minimal residual disease (MRD) status, responses rates and survival outcomes.

II. To evaluate soluble B-cell maturation antigen (sBCMA) levels at baseline and how they correlate to response rates and survival outcomes in patients treated with teclistamab plus iberdomide.

III. To identify the immunophenotypic and transcriptomic characterization of malignant plasma cells that are resistant to teclistamab and iberdomide.

OUTLINE: This is a dose-escalation study of iberdomide in combination with teclistamab.

Patients receive teclistamab subcutaneously (SC) on days 1, 4, 7, 15 and 22 for cycle 1 and days 1, 8, 15 and 22 for subsequent cycles. Patients also receive iberdomide orally (PO) once daily (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 positron emission tomography (PET)/computed tomography (CT) or PET/magnetic resonance imaging (MR) throughout the trial.

After completion of study treatment, patients are followed up every 3-6 months for up to 2 years.

Conditions: Recurrent Multiple Myeloma, Refractory Multiple Myeloma
Being tested: Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Computed Tomography, Iberdomide
Medical subject headings: Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo blood and urine sample collection
Bone Marrow AspirationProcedure or surgery
Undergo bone marrow aspiration and biopsy
Bone Marrow BiopsyProcedure or surgery
Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow
Undergo bone marrow aspiration and biopsy
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo PET/CT
IberdomideDrug
Also called CC 220, CC-220, Zenbexus
Given PO
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo PET/MR
Positron Emission TomographyProcedure or surgery
Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)
Undergo PET/CT or PET/MR
TeclistamabDrug
Also called JNJ 64007957, JNJ-64007957, JNJ64007957, Teclistamab-cqyv
Given SC

Study groups in NCT06465316
Study group	Role	What they receive
Treatment (iberdomide, teclistamab)	Experimental	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. Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Drug: Iberdomide; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography; Drug: Teclistamab

What is being measured

The primary outcome is the main question the study is designed to answer.

Recommended phase 2 dose (RP2D) of iberdomide when combined with teclistamab
The RP2D will be defined as the pharmacologically optimal dose of iberdomide that can be combined with teclistamab and will be selected based on all available pharmacokinetic, pharmacodynamic, target engagement, efficacy, safety and tolerability data.
Measured: At 28 days
Maximum tolerated dose (MTD) of iberdomide when combined with teclistamab
The MTD will be is defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 8 new patients).
Measured: At 28 days

Secondary outcomes (7)

Incidence of adverse events (AEs)
AEs will be described and graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The maximum grade for each type of AE will be recorded for each patient, and frequency tables will be reviewed to determine patterns. The relationship of the AEs to the study treatment will be taken into consideration.
Measured: Up to 4 weeks after last dose of study treatment
Overall response rate (ORR)
The ORR will be estimated by the total number of patients who achieve a stringent complete response, complete response, very good partial response, or partial response divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true overall response rate will be calculated.
Measured: Up to 2 years after last dose of study treatment
Minimal residual disease (MRD) negativity
MRD negativity will be summarized descriptively at each specified timepoint.
Measured: Up to 2 years after last dose of study treatment
Progression-free survival (PFS)
The distribution of PFS will be estimated using the method of Kaplan-Meier.
Measured: From registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 2 years after last dose of study treatment
Time to progression
The distribution of time to progression will be estimated using the method of Kaplan-Meier.
Measured: From registration to the earliest date of documentation of disease progression, assessed up to 2 years after last dose of study treatment
Duration of response (DOR)
The distribution of DOR will be estimated using the method of Kaplan-Meier.
Measured: From earliest documentation of disease response to disease progression, assessed up to 2 years after last dose of study treatment
Overall survival (OS)
The distribution of OS will be estimated using the method of Kaplan-Meier.
Measured: From registration to death due to any cause, assessed up to 2 years after last dose of study treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

6 Dec 202431 Dec 2026

First posted18 Jun 2024
Study start6 Dec 2024
Primary completion31 Dec 2026 (estimated)
Study completion31 Dec 2026 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Recurrent Multiple MyelomaStudies of the same condition, open and under way.
More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 26 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06465316
Sponsor's protocol ID: NCI-2024-04754
Other IDs: NCI-2024-04754, 10620, 10620, UM1CA186709
Status last verified: Sep 2026
First submitted: 17 Jun 2024
Last updated: 22 Oct 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.