Randomized Phase 2 Study of Iberdomide Maintenance Therapy Following Idecabtagene Vicleucel CAR-T in Multiple Myeloma Patients

Status: Recruiting
Location: See all (73) locations...
Intervention Type: Procedure, Drug
Study Type: Interventional
Study Phase: Phase 2
SUMMARY

This phase II trial compares iberdomide maintenance therapy to disease monitoring for improving survival in patients who have received idecabtagene vicleucel (a type of chimeric antigen receptor T-cell \[CAR-T\] therapy) for multiple myeloma. The usual approach after treatment with idecabtagene vicleucel is to monitor the multiple myeloma without giving myeloma medications. There is currently no medication approved specifically for use after idecabtagene vicleucel treatment. Upon administration, iberdomide modifies the immune system and activates immune cells called T-cells, which could enhance the effectiveness of idecabtagene vicleucel. Iberdomide may keep multiple myeloma under control for longer than the usual approach (disease monitoring) after idecabtagene vicleucel, and may help multiple myeloma patients live longer.

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

• PRE-REGISTRATION ELIGIBILITY CRITERIA (STEP 0):

• All patients must be pre-registered. For patients who consent to biobanking, submit the bone marrow and blood specimens

‣ Note: Patients who do not consent to the optional biobanking must be pre-registered, but specimens should not be submitted for these patients

⁃ Please ensure patient has suspected diagnosis of multiple myeloma and meets on study guidelines prior to informed consent and biospecimen collection

⁃ In cases where the bone marrow aspiration may be inadequate at Step 0 registration, the patient may still register on study

• ELIGIBILITY CRITERIA (STEP 1):

• Patients must have diagnostically confirmed MM in response status of stable disease or better by International Myeloma Working Group (IMWG) criteria at day 80-110 post-infusion of ide-cel. Patients in deep remission (e.g., CR, MRD-negative, etc.), are eligible

• All patients are required to have received ide-cel CAR-T within 80-110 days of registration

• Adverse events related to ide-cel are required to have resolved to grade =\< 1 except fatigue, alopecia, and other events that are unlikely to interfere with study assessments or pose a safety risk to participants

• Patients must have had ≥ 4 lines of therapy for MM (this includes proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody)

• Prior therapy with iberdomide is permitted but prior iberdomide refractoriness is prohibited. Refractoriness is defined as per published IMWG criteria; progression while on iberdomide or within 60 days of stopping iberdomide

• Patients who have received MM-directed therapy since ide-cel infusion are not eligible, with the exception of short-course steroids for managing ide-cel toxicity as described below

• Age ≥ 18 years

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

• Absolute neutrophil count (ANC) ≥ 1,500/mm\^3

‣ Platelet transfusions or use of growth factors for neutropenia (e.g., filgrastim, tbo-filgrastim, sagramostim) are not permitted to meet enrollment criteria

• Platelet count ≥ 75,000/mm\^3

‣ Platelet transfusions or use of growth factors for neutropenia (e.g., filgrastim, tbo-filgrastim, sagramostim) are not permitted to meet enrollment criteria

• Calculated (calc.) creatinine clearance \>= 30 mL/min by Modification of Diet in Renal Disease (MDRD)

‣ Platelet transfusions or use of growth factors for neutropenia (e.g., filgrastim, tbo-filgrastim, sagramostim) are not permitted to meet enrollment criteria

• Total bilirubin ≤ 1.5 x upper limit of normal (ULN)

‣ Platelet transfusions or use of growth factors for neutropenia (e.g., filgrastim, tbo-filgrastim, sagramostim) are not permitted to meet enrollment criteria

• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) ≤ 3 x upper limit of normal (ULN)

‣ Platelet transfusions or use of growth factors for neutropenia (e.g., filgrastim, tbo-filgrastim, sagramostim) are not permitted to meet enrollment criteria

• Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effect on the developing fetus and newborn are unknown.

‣ FCBP (female of childbearing potential) is a female who: 1) has achieved menarche (first menstrual cycle) at some point, 2) has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time during the preceding 24 consecutive months).

⁃ Females of childbearing potential (FCBP):

• Must use a contraceptive method that is highly effective (with a failure rate of \< 1% per year), preferably with low user dependency during the intervention period and for at least 28 days after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.

∙ The effects of iberdomide on the developing human fetus are unknown. Immunodulatory derivative (IMiD) agents as well as other therapeutic agents used in this trial are known to be teratogenic. Females of child-bearing potential (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, and again within 24 hours of starting iberdomide, and 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 she starts taking iberdomide. 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 agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risk of fetal exposure.

∙ Should a woman become pregnant or suspect she is pregnant while she or her partner are participating in this study, she should inform her treating physician immediately. FCBP must use adequate contraception for at least 28 days after discontinuation from study. Because of the potential for serious adverse reactions in a breastfed child, women are advised not to breastfeed during treatment and for at least 28 days after the last dose.

∙ The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with a nearly undetected pregnancy.

⁃ Non-childbearing potential is defined as follows (by other than medical reasons):

• ≥ 45 years of age and has not had menses for \> 1 year

∙ Patients who have been amenorrhoeic for \< 2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation

∙ Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure

• Male patients must agree to use an adequate method of contraception for the duration of the study and for 28 days afterwards.

‣ Male participants: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies:

• Male participants are eligible to participate if they agree to the following during the intervention period and for 28 days after the last dose of study treatment to allow for clearance of any altered sperm:

⁃ Refrain from donating sperm

‣ PLUS, either:

• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR

• Must agree to use contraception/barrier as detailed below:

‣ Agree to use a male condom, even if they have undergone a successful vasectomy, and female partner to use an additional highly effective contraceptive method with a failure rate of \< 1% per year as when having sexual intercourse with a woman of childbearing potential (including pregnant females)

• Patients may not have polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome or amyloidosis involving any vital organ; amyloidosis found in skin or lymph nodes (non-vital organs), or incidental observation of amyloidosis on bone marrow biopsy, are both permissible. Plasma cell leukemia is permissible for study enrollment

∙ 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

∙ Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration 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. Patients with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load

∙ Patients may not have other, active infections at time of study registration. Recent infections are not exclusionary if antibiotics have been completed and infection is considered to be resolved / controlled. (Chronic maintenance antibiotics for prior infections, such as fungal, are permissible.)

∙ No known allergy to iberdomide

∙ No known medical condition causing an inability to swallow oral formulations of agents

∙ Patients receiving other active therapies for MM since ide-cel infusion are prohibited from participating in the study

∙ Corticosteroids used for the purpose of managing ide-cel toxicity (often neurotoxicity) soon after ide-cel administration are acceptable, provided that the participant will have been off corticosteroids for \> 30 days by cycle 1 day 1. Physiologically dosed chronic steroids are permitted

∙ Given the potential for interaction with iberdomide, patients who take strong CYP3A4 inducers or inhibitors may enroll after switching to a different agent and after an appropriate washout period for that particular medication, ideally three half-lives, prior to cycle 1 day 1

Locations
United States
California
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
RECRUITING
Irvine
Cedars Sinai Medical Center
RECRUITING
Los Angeles
UC Irvine Health/Chao Family Comprehensive Cancer Center
RECRUITING
Orange
University of California Davis Comprehensive Cancer Center
RECRUITING
Sacramento
Georgia
Augusta University Medical Center
RECRUITING
Augusta
Iowa
UI Health Care Mission Cancer and Blood - Ankeny Clinic
RECRUITING
Ankeny
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
RECRUITING
Clive
Iowa Methodist Medical Center
RECRUITING
Des Moines
Mercy Medical Center - Des Moines
RECRUITING
Des Moines
UI Health Care Mission Cancer and Blood - Des Moines Clinic
RECRUITING
Des Moines
UI Health Care Mission Cancer and Blood - Laurel Clinic
RECRUITING
Des Moines
UI Health Care Mission Cancer and Blood - Waukee Clinic
RECRUITING
Waukee
Illinois
University of Illinois
SUSPENDED
Chicago
Missouri
Siteman Cancer Center at Saint Peters Hospital
RECRUITING
City Of Saint Peters
Siteman Cancer Center at West County Hospital
RECRUITING
Creve Coeur
Siteman Cancer Center at Christian Hospital
RECRUITING
St Louis
Siteman Cancer Center-South County
RECRUITING
St Louis
Washington University School of Medicine
RECRUITING
St Louis
Mississippi
Baptist Memorial Hospital and Cancer Center-Desoto
RECRUITING
Southhaven
North Carolina
UNC Lineberger Comprehensive Cancer Center
SUSPENDED
Chapel Hill
Atrium Health Pineville/LCI-Pineville
RECRUITING
Charlotte
Atrium Health University City/LCI-University
RECRUITING
Charlotte
Carolinas Medical Center/Levine Cancer Institute
RECRUITING
Charlotte
Atrium Health Cabarrus/LCI-Concord
RECRUITING
Concord
Levine Cancer Institute - Huntersville
RECRUITING
Huntersville
Atrium Health Union/LCI-Union
RECRUITING
Monroe
Wake Forest University Health Sciences
RECRUITING
Winston-salem
North Dakota
Sanford Broadway Medical Center
RECRUITING
Fargo
Sanford Roger Maris Cancer Center
RECRUITING
Fargo
Nebraska
Nebraska Medicine-Bellevue
RECRUITING
Bellevue
Nebraska Medicine-Village Pointe
RECRUITING
Omaha
University of Nebraska Medical Center
RECRUITING
Omaha
New Jersey
Memorial Sloan Kettering Monmouth
RECRUITING
Middletown
Memorial Sloan Kettering Bergen
RECRUITING
Montvale
New York
Memorial Sloan Kettering Commack
RECRUITING
Commack
Memorial Sloan Kettering Westchester
RECRUITING
Harrison
Memorial Sloan Kettering Cancer Center
RECRUITING
New York
Oklahoma
University of Oklahoma Health Sciences Center
SUSPENDED
Oklahoma City
Oregon
Providence Portland Medical Center
RECRUITING
Portland
Providence Saint Vincent Medical Center
RECRUITING
Portland
Pennsylvania
Geisinger Medical Center
RECRUITING
Danville
South Carolina
Prisma Health Cancer Institute - Eastside
RECRUITING
Greenville
Tennessee
Baptist Memorial Hospital and Cancer Center-Memphis
RECRUITING
Memphis
Texas
Houston Methodist San Jacinto Hospital
RECRUITING
Baytown
Houston Methodist Cypress Hospital
RECRUITING
Cypress
Houston Methodist Hospital
RECRUITING
Houston
Houston Methodist West Hospital
RECRUITING
Houston
Methodist Willowbrook Hospital
RECRUITING
Houston
Houston Methodist Saint John Hospital
RECRUITING
Nassau Bay
Houston Methodist Sugar Land Hospital
RECRUITING
Sugar Land
Houston Methodist The Woodlands Hospital
RECRUITING
The Woodlands
Vermont
University of Vermont and State Agricultural College
RECRUITING
Burlington
University of Vermont Medical Center
RECRUITING
Burlington
Washington
Swedish Cancer Institute-Edmonds
RECRUITING
Edmonds
Swedish Cancer Institute-Issaquah
RECRUITING
Issaquah
Swedish Medical Center-First Hill
RECRUITING
Seattle
Wisconsin
Aurora Cancer Care-Southern Lakes VLCC
RECRUITING
Burlington
Aurora Saint Luke's South Shore
RECRUITING
Cudahy
Aurora Health Care Germantown Health Center
RECRUITING
Germantown
Aurora Cancer Care-Grafton
RECRUITING
Grafton
Aurora BayCare Medical Center
RECRUITING
Green Bay
Aurora Cancer Care-Kenosha South
RECRUITING
Kenosha
Aurora Bay Area Medical Group-Marinette
RECRUITING
Marinette
Aurora Cancer Care-Milwaukee
RECRUITING
Milwaukee
Aurora Saint Luke's Medical Center
RECRUITING
Milwaukee
Aurora Sinai Medical Center
RECRUITING
Milwaukee
Vince Lombardi Cancer Clinic - Oshkosh
RECRUITING
Oshkosh
Aurora Cancer Care-Racine
RECRUITING
Racine
Vince Lombardi Cancer Clinic-Sheboygan
RECRUITING
Sheboygan
Aurora Medical Center in Summit
RECRUITING
Summit
Vince Lombardi Cancer Clinic-Two Rivers
RECRUITING
Two Rivers
Aurora Cancer Care-Milwaukee West
RECRUITING
Wauwatosa
Aurora West Allis Medical Center
RECRUITING
West Allis
Time Frame
Start Date: 2024-08-27
Estimated Completion Date: 2027-10-31
Participants
Target number of participants: 78
Treatments
Active_comparator: Group 1 (monitoring)
Patients undergo disease monitoring at monthly clinic visits until disease progression. Patients also undergo bone marrow aspiration and biopsy throughout the trial, undergo collection of blood samples at screening and on study, and undergo PET/CT and/or skeletal survey x-ray, CT, or MRI at screening and then as clinically indicated.
Experimental: Group II (iberdomide)
Patients receive iberdomide PO QD on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and biopsy throughout the trial, undergo collection of blood samples at screening and on study, and undergo PET/CT and/or skeletal survey x-ray, CT, or MRI at screening and then as clinically indicated.
Sponsors
Leads: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov