Trial Title:
Iberdomide-dexamethasone Alone or in Combination With Standard MM Treatment Regimens in Transplant Ineligible Newly Diagnosed Patients.
NCT ID:
NCT05527340
Condition:
Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Dexamethasone
Daratumumab
Conditions: Keywords:
De novo Multiple Myeloma
Transplant ineligible
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Iberdomide
Description:
Iberdomide on days 1 to 21 at 1.6 mg, every 4 weeks, orally (PO)
Arm group label:
iberdomide + daratumumab + dexamethasone (IBERDARADEX)
Arm group label:
iberdomide + dexamethasone (IBERDEX)
Intervention type:
Drug
Intervention name:
Dexamethasone
Description:
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.
Arm group label:
iberdomide + daratumumab + dexamethasone (IBERDARADEX)
Arm group label:
iberdomide + dexamethasone (IBERDEX)
Intervention type:
Drug
Intervention name:
Daratumumab
Description:
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).
Arm group label:
iberdomide + daratumumab + dexamethasone (IBERDARADEX)
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.
Detailed description:
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.
Criteria for eligibility:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Hospital Universitario de Canarias
Address:
City:
La Laguna
Country:
Spain
Contact:
Last name:
Sunil Lakhwani
Investigator:
Last name:
Sunil Lakhwani
Email:
Principal Investigator
Facility:
Name:
Hospital General Universitario Gregorio Marañón
Address:
City:
Madrid
Country:
Spain
Contact:
Last name:
Cristina Encinas Rodríguez
Investigator:
Last name:
Cristina Encinas Rodríguez
Email:
Principal Investigator
Facility:
Name:
Hospital Universitario 12 de Octubre
Address:
City:
Madrid
Country:
Spain
Contact:
Last name:
Joaquín Martínez López
Investigator:
Last name:
Joaquín Martínez López
Email:
Principal Investigator
Facility:
Name:
Hospital Son Llatzer
Address:
City:
Palma De Mallorca
Country:
Spain
Contact:
Last name:
Joan Bargay Llenonart
Investigator:
Last name:
Joan Bargay Llenonart
Email:
Principal Investigator
Facility:
Name:
Clínica Universidad de Navarra
Address:
City:
Pamplona
Country:
Spain
Contact:
Last name:
Paula Rodríguez Otero
Investigator:
Last name:
Paula Rodríguez Otero
Email:
Principal Investigator
Facility:
Name:
Hospital Universitario de Salamanca
Address:
City:
Salamanca
Country:
Spain
Contact:
Last name:
Maria Victoria Mateos Manteca
Investigator:
Last name:
Maria Victoria Mateos Manteca
Email:
Principal Investigator
Facility:
Name:
Hospital Universitario Marqués de Valdecilla
Address:
City:
Santander
Country:
Spain
Contact:
Last name:
Enrique Ocio San Miguel
Investigator:
Last name:
Enrique Ocio San Miguel
Email:
Principal Investigator
Facility:
Name:
Hospital Universitario Virgen del Rocío
Address:
City:
Sevilla
Country:
Spain
Contact:
Last name:
Marta Reinosa Segura
Investigator:
Last name:
Marta Reinosa Segura
Email:
Principal Investigator
Facility:
Name:
Hospital Universitario y Politécnico La Fe de Valencia
Address:
City:
Valencia
Country:
Spain
Contact:
Last name:
Javier de la Rubia Comos
Investigator:
Last name:
Javier de la Rubia Comos
Email:
Principal Investigator
Start date:
September 2022
Completion date:
December 2029
Lead sponsor:
Agency:
PETHEMA Foundation
Agency class:
Other
Collaborator:
Agency:
Celgene-BMS
Agency class:
Other
Collaborator:
Agency:
Janssen-Cilag, S.A.
Agency class:
Industry
Collaborator:
Agency:
LIDESEC
Agency class:
Other
Source:
PETHEMA Foundation
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05527340
