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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05527340
Recruitment Status : Not yet recruiting
First Posted : September 2, 2022
Last Update Posted : September 2, 2022
Sponsor:
Collaborators:
Celgene-BMS
Janssen-Cilag, S.A.
LIDESEC
Information provided by (Responsible Party):
PETHEMA Foundation

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Iberdomide Drug: Dexamethasone Drug: Daratumumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multicenter, Phase II, National and Open-label Study to Evaluate Iberdomide-dexamethasone Alone or in Combination With Standard MM Treatment Regimens in Transplant Ineligible Newly Diagnosed Patients.
Estimated Study Start Date : September 2022
Estimated Primary Completion Date : December 2029
Estimated Study Completion Date : December 2029


Arm Intervention/treatment
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.
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.

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).
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).




Primary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: Throught the study period. Approximately 6 years. ]
    The percentage of participants with a confirmed partial response (PR) or better (PR, Very good partial response (VGPR), Complete response (CR), stringent complete response (sCR)).Response rates will be monitored monthly, but the study will report the % of patients achieving CR rate at month 12, 18, 24 and yearly thereafter.

  2. Complete Response Rate (CRR) [ Time Frame: Throught the study period. Approximately 6 years. ]
    The percentage of participants with a confirmed complete response (CR) or better (stringent complete response (CR, sCR).


Secondary Outcome Measures :
  1. Minimal Residual Disease (MRD) negativity rate [ Time Frame: Throught the study period. Approximately 6 years. ]
    The percentage of participants who are MRD negative by next-generation flow cytometry (NGF), PET/CT, and mass spectrometry.

  2. Progression-Free Survival (PFS) [ Time Frame: Throught the study period. Approximately 6 years. ]
    Time from the date of randomization until the earliest date of documented disease progression or death due to any cause.

  3. Overall Survival (OS) [ Time Frame: Throught the study period. Approximately 6 years. ]
    Time from the date of randomization until the date of death due to any cause

  4. Changes in the immune profiling. [ Time Frame: Throught the study period. Approximately 6 years. ]
    Relative distribution and immunophenotype of inmune profiling from baseline onto treatment, remission and disease progression.

  5. Health status/quality of life [ Time Frame: Baseline and throught the first 24 months. ]
    Global health status/quality of life based on patient reported outcome: EQ-5D/5L questionnaire.

  6. Health status/quality of life [ Time Frame: Baseline and throught the first 24 months. ]
    Global health status/quality of life based on patient reported outcome: QLQ-C30 questionnaire.

  7. Health status/quality of life [ Time Frame: Baseline and throught the first 24 months. ]
    Global health status/quality of life based on patient reported outcome: MY20 questionnaire.

  8. Frequency and percentage of deaths and primary cause of death. [ Time Frame: Throught the study period. Approximately 6 years. ]
    Incidence of deaths and primary cause of death for safety analysis.

  9. Incidence of adverse events (AEs). [ Time Frame: Throught the treatment period. Approximately 4 years. ]
    Incidence of adverse events (AEs).

  10. Percentage of patients discontinuing therapy due to AEs. [ Time Frame: Throught the treatment period. Approximately 4 years. ]
    Percentage of patients discontinuing therapy due to AEs.

  11. Percentage of patients requiring dose modifications. [ Time Frame: Throught the treatment period. Approximately 4 years. ]
    Percentage of patients requiring dose modifications.

  12. Percentage of patients with changes in laboratory analytes from the hematology and blood chemistry panel. [ Time Frame: Throught the treatment period. Approximately 4 years. ]
    Percentage of patients with changes in laboratory analytes from the hematology and blood chemistry panel.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05527340


Contacts
Layout table for location contacts
Contact: Carmen López-Carrero (+34) 699 835 437 carmen@fundacionpethema.es
Contact: Roberto Maldonado (+34) 683 15 66 87 roberto.maldonado@fundacionpethema.es

Locations
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Spain
Hospital Universitario de Canarias
La Laguna, Spain
Contact: Sunil Lakhwani         
Principal Investigator: Sunil Lakhwani         
Hospital General Universitario Gregorio Marañón
Madrid, Spain
Contact: Cristina Encinas Rodríguez         
Principal Investigator: Cristina Encinas Rodríguez         
Hospital Universitario 12 de Octubre
Madrid, Spain
Contact: Joaquín Martínez López         
Principal Investigator: Joaquín Martínez López         
Hospital Son Llatzer
Palma De Mallorca, Spain
Contact: Joan Bargay Llenonart         
Principal Investigator: Joan Bargay Llenonart         
Clínica Universidad de Navarra
Pamplona, Spain
Contact: Paula Rodríguez Otero         
Principal Investigator: Paula Rodríguez Otero         
Hospital Universitario de Salamanca
Salamanca, Spain
Contact: Maria Victoria Mateos Manteca         
Principal Investigator: Maria Victoria Mateos Manteca         
Hospital Universitario Marqués de Valdecilla
Santander, Spain
Contact: Enrique Ocio San Miguel         
Principal Investigator: Enrique Ocio San Miguel         
Hospital Universitario Virgen del Rocío
Sevilla, Spain
Contact: Marta Reinosa Segura         
Principal Investigator: Marta Reinosa Segura         
Hospital Universitario y Politécnico La Fe de Valencia
Valencia, Spain
Contact: Javier de la Rubia Comos         
Principal Investigator: Javier de la Rubia Comos         
Sponsors and Collaborators
PETHEMA Foundation
Celgene-BMS
Janssen-Cilag, S.A.
LIDESEC
Investigators
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Study Chair: María Victoria Mateos Manteca University of Salamanca
Study Chair: Verónica González de la Calle University of Salamanca
Study Chair: Jesús San Miguel Izquierdo Clínica Universidad de Navarra
Study Chair: Juan José Lahuerta Palacios Hospital Universitario 12 de Octubre
Study Chair: Joan Bladé Creixenti Hospital Clinic of Barcelona
Publications:
Burtis CA, Ashwood ER. Tietz Textbook of Clinical Chemistry, 3rd ed. Philadelphia; WB Saunders, 1998.

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Responsible Party: PETHEMA Foundation
ClinicalTrials.gov Identifier: NCT05527340    
Other Study ID Numbers: GEM-IBERDARAX
2021-002190-25 ( EudraCT Number )
First Posted: September 2, 2022    Key Record Dates
Last Update Posted: September 2, 2022
Last Verified: September 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by PETHEMA Foundation:
De novo Multiple Myeloma
Transplant ineligible
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Daratumumab
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents