Iberdomide-dexamethasone Alone or in Combination With Standard MM Treatment Regimens in Transplant Ineligible Newly Diagnosed Patients.

Study Purpose

This is a multicenter, phase II, national, and open-label study to evaluate the efficacy and safety of two different combinations, iberdomide-dexamethasone (IBERDEX) and iberdomide-dexamethasone in combination with daratumumab (IBERDARADEX) in transplant ineligible newly diagnosed multiple myeloma (NDMM) patients. It will be ensured that at least 30% of the patients are frail in order to evaluate the feasibility of these combinations in this special population. Patients will receive treatment with either iberdomide + dexamethasone (IBERDEX) or iberdomide + daratumumab + dexamethasone (IBERDARADEX), until unacceptable toxicity, disease progression, patient withdrawal, loss to follow-up, end of study or death, whichever comes first. This is not a randomized trial so eligible patients will be sequentially allocated to receive iberdomide-dexamethasone or iberdomide-dexamethasone plus daratumumab.

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. Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements. 2. Patient must be able to understand the study procedures. 3. Patient has given voluntary written informed consent before performance of any study-related procedure nor part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care. 4. Newly diagnosed multiple myeloma patient ≥65 years or younger but non-transplant eligible who requires start active treatment according to the IMWG published in 2014. 5. Patient must have a measurable secretory disease defined as either serum monoclonal protein of ≥ 0,5 g/dl or urine monoclonal (light chain) protein ≥ 200 mg/24 h. For patients whose disease is only measurable by serum FLC, the involved FLC should be ≥ 10mg/L (100 mg/dl), with an abnormal serum FLC ratio. 6. Patient is defined as non-frail or frail using the modified-IMWG scale (APPENDIX 5). Frailty score according to the modified-IMWG scale will be collected before starting the treatment in order to ensure 30% of the patients are frail. 7. Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2. 8. Patient must be ≥ 18 years of age. 9. Patient must have adequate organ function, 10. Female childbearing potential patient (FCBP) criteria: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. A female patient is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
  • - Is not a female of childbearing potential (FNCBP) OR.
  • - Is a FCBP and.
  • - She understands the potential teratogenic risk to the unborn child.
  • - She understands the need for effective contraception, without interruption, 28 days before starting study treatment, throughout the entire duration of study treatment, during dose interruptions and for at least 3 months after the last dose of study treatment.
  • - She understands and agrees to inform the Investigator if a change or stop of method of contraception is needed.
  • - She must be capable of complying with effective contraceptive measures.
  • - She is informed and understands the potential consequences of pregnancy and the need to notify her study doctor immediately if there is a risk of pregnancy.
  • - She understands the need to commence study treatment as soon as it is dispensed following a negative pregnancy test.
  • - She understands and accepts the need to undergo pregnancy testing based on the frequency outlined in this plan.
  • - She acknowledges she understands the hazards study drugs can cause to an unborn fetus and the necessary precautions associated with the use of study drugs.
The Investigator must ensure that a FCBP:
  • - Complies with the conditions of the pregnancy prevention plan, including confirmation that she has an adequate level of understanding.
  • - Acknowledges the aforementioned requirements.
A FCBP must have a negative highly sensitive serum pregnancy test (as required by local regulations) within 24 hours before the first dose of study drug(s). Non-childbearing potential is defined as follows (by other than medical reasons):
  • - Has not achieved menarche at some point.
  • - Has undergone a hysterectomy or bilateral oophorectomy.
  • - Has 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 in the preceding 24 consecutive months).
11. Male patient: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male patient is eligible to participate if he agrees to the following during dose interruptions and for at least 3 months following the last dose of iberdomide to allow for clearance of any altered sperm:
  • - Understand the potential teratogenic risk if engaged in sexual activity with a pregnant female or a FCBP.
  • - Understand the need for the use of a condom even if he has had a vasectomy, if engaged in sexual activity with a pregnant female or a FCBP.
  • - Understand the potential teratogenic risk if the subject donates semen or sperm.
  • - Understand that the effects on fertility are currently unknown, therefore all family planning options and/or alternatives should be thoroughly discussed with the study doctor prior to receiving study drugs.
12. All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 5.0 must be ≤ Grade 1 at the time of enrolment except for alopecia.

Exclusion Criteria:

1. Patient has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), plasma cell leukemia or active POEMS syndrome at the time of screening. 2. Patient has had clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS multiple myeloma. 3. Patient has invasive malignancies other than disease under study, unless the second malignancy has been medically stable for at least 2 years and, in the opinion of the principal investigators, will not affect the evaluation of the effects of clinical trial treatments on the currently targeted malignancy. Participants with curatively treated non-melanoma skin cancer may be enrolled without a 2-year restriction. 4. Any serious medical condition that places the subject at an unacceptable risk if he or she participates in this study; subjects with conditions requiring chronic steroid or immunosuppressive treatment, such as rheumatoid arthritis, multiple sclerosis and lupus, that likely need additional steroid or immunosuppressive treatments in addition to the study treatment. 5. Pregnant or breastfeeding females. 6. Patient is simultaneously enrolled in other interventional clinical trial. 7. Received plasmapheresis within 7 days prior to the first dose of study drug. 8. Patient has received prior radiotherapy within 2 weeks of start of study therapy. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease. 9. Patient has a known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to iberdomide or drugs chemically related to iberdomide, or any of the excipients contained in the formulation of the study treatment. 10. Patient has a known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to daratumumab or drugs chemically related to daratumumab, or any of the excipients contained in the formulation of the study treatment. 11. Participant has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to other monoclonal antibodies. 12. Patient has a known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to dexamethasone or drugs chemically related to dexamethasone, or any of the excipients contained in the formulation of the study treatment. 13. Major surgery (except kyphoplasty) ≤ 4 weeks prior to initiating protocol therapy. 14. Patient has peripheral neuropathy or neuropathic pain grade ≥2, as defined by the National Cancer Institute Terminology Criteria for Adverse Events (NCI CTC AE) Version 5.0. 15. Patient evidence of cardiovascular risk including any of the following:
  • - QTcF interval QTcF > 480 msec (the QT interval values must be corrected for heart rate by Fridericia's formula [QTcF]) - Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (Type II) or 3rd degree atrioventricular (AV) block.
  • - History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within six months of Screening.
  • - Class III or IV heart failure as defined by the New York Heart Association functional classification system [NYHA, 1994] - Uncontrolled hypertension, defined as an average systolic blood pressure ≥ 160 mmHg or diastolic ≥ 100 mmHg despite optimal treatment.
16. Patient has current unstable liver or biliary disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Note: Stable chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if otherwise meets entry criteria. 17. Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect patient's safety). Participants with isolated proteinuria resulting from MM are eligible, provided they fulfil inclusion criteria. 18. Evidence of active mucosal or internal bleeding. 19. Any serious medical condition or psychiatric illness that would interfere in understanding of the informed consent form. 20. Uncontrolled endocrine diseases (i.e. diabetes mellitus, hypothyroidism or hyperthyroidism) (i.e. requiring relevant changes in medication within the last month, or hospital admission within the last 3 months). 21. Patients with acute diffuse infiltrative pulmonary disease and/or pericardial disease. 22. Patients with severe chronic obstructive pulmonary disease (COPD) or asthma with forced expiratory volume in the first minute (FEV1) less than 50%. 23. History of interstitial lung disease or ongoing interstitial lung disease. 24. Patient has an active infection requiring antibiotic, antiviral, or antifungal treatment. 25. Participant has known HIV infection. 26. Patient has presence of hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb) at screening or within 3 months prior to first dose of study treatment. aa.Patient has positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study treatment. Note: Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained. Note: Hepatitis RNA testing is optional and participants with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing.

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.

NCT05527340
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 2
Lead Sponsor

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

PETHEMA Foundation
Principal Investigator

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

María Victoria Mateos MantecaVerónica González de la CalleJesús San Miguel IzquierdoJuan José Lahuerta PalaciosJoan Bladé Creixenti
Principal Investigator Affiliation University of SalamancaUniversity of SalamancaClínica Universidad de NavarraHospital Universitario 12 de OctubreHospital Clinic of Barcelona
Agency Class

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

Other, Industry
Overall Status Not yet recruiting
Countries Spain
Conditions

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

Multiple Myeloma
Additional Details

This is a multicenter, phase II, national, and open-label study to evaluate the efficacy and safety of two different combinations, iberdomide-dexamethasone (IBERDEX) and iberdomide-dexamethasone in combination with daratumumab (IBERDARADEX) in transplant ineligible newly diagnosed multiple myeloma (NDMM) patients. It will be ensured that at least 30% of the patients are frail in order to evaluate the feasibility of these combinations in this special population. Patients will receive treatment with either iberdomide + dexamethasone (IBERDEX) or iberdomide + daratumumab + dexamethasone (IBERDARADEX), until unacceptable toxicity, disease progression, patient withdrawal, loss to follow-up, end of study or death, whichever comes first. This is not a randomized trial so eligible patients will be sequentially allocated to receive iberdomide-dexamethasone or iberdomide-dexamethasone plus daratumumab. Participants will be evaluated for study eligibility per protocol as defined in the Inclusion/Exclusion criteria . The screening period takes place 28 days prior to the baseline visit. Frontline treatment: cohorts 1 and 2. Cohort 1: IBERDEX.

  • - Iberdomide on days 1 to 21 at 1.6 mg, every 4 weeks, orally (PO).
  • - Dexamethasone will be given on days 1, 8, 15, and 22 at 40 mg (patients aged ≥ 75 years: 20 mg), every 4 weeks, PO.
Cohort 2: IBERDARADEX.
  • - Iberdomide on days 1 to 21 at 1.6 mg, every 4 weeks, PO.
  • - Dexamethasone will be given on days 1, 8, 15, and 22 at 40 mg (patients aged ≥ 75 years: 20 mg), every 4 weeks, PO.
  • - Daratumumab will be given at 1800 mg, every 4 weeks, subcutaneously (SC).
Cycles 1 and 2 (C1 and C2): Days 1, 8, 15, and 22 C3-6: Days 1 and 15 From C7 onwards: Day 1 of each cycle. The study treatment in both cohorts will be until unacceptable toxicity, disease progression, patient withdrawal, loss to follow-up, end of study or death, whichever comes first. The trial has the following objectives: Primary Objectives. PO1: To determine the efficacy of iberdomide in combination with dexamethasone (IBERDEX cohort 1) and also in combination with daratumumab and dexamethasone (IBERDARADEX cohort 2) in transplant ineligible NDMM patients, as measured by overall response rate (ORR) as well as the other response categories and especially the complete response rate (CRR) according to the International Myeloma Working Group (IMWG) response criteria 2016. Secondary Objectives. SO1: To evaluate the efficacy in terms of minimal residual disease (MRD) with especial attention to the proportion of patients in MRD negative at 12 months of starting treatment as well as patients able to sustain it over time (according to the IMWG response criteria 2016). SO2: To evaluate time to event data in the overall population and in the frail and non-frail population: Progression Free Survival (PFS) (from the time of inclusion in the trial until progression and/or death) and Overall Survival (OS). SO3: To evaluate the changes in the immune profiling in order to better understand the outcomes in the overall population and in the non-frail and frail subgroups of patients. SO4: To assess quality of life evolution through EQ-5D/5L, QLQ-C30 and MY20 questionnaires, at baseline and at months 4, 8, 12, 18, and 24. SO5: To assess the safety of the combination of iberdomide + dexamethasone and iberdomide + dexamethasone + daratumumab.

Arms & Interventions

Arms

Experimental: iberdomide + dexamethasone (IBERDEX)

IBERDEX Iberdomide on days 1 to 21 at 1.6 mg, every 4 weeks, orally (PO). Dexamethasone will be given on days 1, 8, 15, and 22 at 40 mg (patients aged ≥ 75 years: 20 mg), every 4 weeks, PO.

Experimental: iberdomide + daratumumab + dexamethasone (IBERDARADEX)

IBERDARADEX Iberdomide on days 1 to 21 at 1.6 mg, every 4 weeks, PO. Dexamethasone will be given on days 1, 8, 15, and 22 at 40 mg (patients aged ≥ 75 years: 20 mg), every 4 weeks, PO. Daratumumab will be given at 1800 mg, every 4 weeks, subcutaneously (SC). Cycles 1 and 2 (C1 and C2): Days 1, 8, 15, and 22 C3-6: Days 1 and 15 From C7 onwards: Day 1 of each cycle Cycles will be of 4 weeks of duration (28 days).

Interventions

Drug: - Iberdomide

Iberdomide on days 1 to 21 at 1.6 mg, every 4 weeks, orally (PO)

Drug: - Dexamethasone

Dexamethasone 40 mg (PO) (or 20 mg (PO) if patient ≥ 75 years old) should be administered on the days 1, 8, 15 and 22 of every 4-week cycle.

Drug: - Daratumumab

Daratumumab will be given at 1800 mg, every 4 weeks, subcutaneously (SC). Cycles 1 and 2 (C1 and C2): Days 1, 8, 15, and 22 C3-6: Days 1 and 15 From C7 onwards: Day 1 of each cycle Cycles will be of 4 weeks of duration (28 days).

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.

International Sites

Hospital Universitario de Canarias, La Laguna, Spain

Status

Address

Hospital Universitario de Canarias

La Laguna, ,

Site Contact

Sunil Lakhwani

carmen@fundacionpethema.es

(+34) 699 835 437

Madrid, Spain

Status

Address

Hospital General Universitario Gregorio Marañón

Madrid, ,

Site Contact

Cristina Encinas Rodríguez

carmen@fundacionpethema.es

(+34) 699 835 437

Hospital Universitario 12 de Octubre, Madrid, Spain

Status

Address

Hospital Universitario 12 de Octubre

Madrid, ,

Site Contact

Joaquín Martínez López

carmen@fundacionpethema.es

(+34) 699 835 437

Hospital Son Llatzer, Palma De Mallorca, Spain

Status

Address

Hospital Son Llatzer

Palma De Mallorca, ,

Site Contact

Joan Bargay Llenonart

carmen@fundacionpethema.es

(+34) 699 835 437

Clínica Universidad de Navarra, Pamplona, Spain

Status

Address

Clínica Universidad de Navarra

Pamplona, ,

Site Contact

Paula Rodríguez Otero

carmen@fundacionpethema.es

(+34) 699 835 437

Hospital Universitario de Salamanca, Salamanca, Spain

Status

Address

Hospital Universitario de Salamanca

Salamanca, ,

Site Contact

Maria Victoria Mateos Manteca

carmen@fundacionpethema.es

(+34) 699 835 437

Santander, Spain

Status

Address

Hospital Universitario Marqués de Valdecilla

Santander, ,

Site Contact

Enrique Ocio San Miguel

carmen@fundacionpethema.es

(+34) 699 835 437

Hospital Universitario Virgen del Rocío, Sevilla, Spain

Status

Address

Hospital Universitario Virgen del Rocío

Sevilla, ,

Site Contact

Marta Reinosa Segura

carmen@fundacionpethema.es

(+34) 699 835 437

Valencia, Spain

Status

Address

Hospital Universitario y Politécnico La Fe de Valencia

Valencia, ,

Site Contact

Javier de la Rubia Comos

carmen@fundacionpethema.es

(+34) 699 835 437