Trial Title:
Iberdomide, Daratumumab, Carfilzomib, and Dexamethasone (Iber-KDd) in Patients With Relapsed/Refractory Multiple Myeloma
NCT ID:
NCT05896228
Condition:
Refractory Multiple Myeloma
Relapsed Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Acetaminophen
Diphenhydramine
Promethazine
Dexamethasone
Daratumumab
Montelukast
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Iberdomide
Description:
Participants will receive Iberdomide (Iber) therapy orally (PO) in capsules as follows:
- Combination therapy: Cycles 1 to 8: 1 mg per day*, Days 1 to 21 every 28 days.
- Monotherapy: Cycles 9 to 20: 1 mg per day*, Days 1 to 21 every 28 days.
(*) The first 6 patients will begin at 1 mg/day as lead-in with option to increase to 1.3
mg with dose-escalation cohort after two (2) cycles tolerated therapy
Arm group label:
Iber Monotherapy
Arm group label:
Iber-KDd Combination Therapy
Intervention type:
Drug
Intervention name:
Carfilzomib
Description:
Participants will receive Carfilzomib (K) therapy intravenously (IV) as follows:
- Cycle 1: 20 mg/m2 per dose on Day 1; 56 mg/m2 per dose on Days 8 and 15
- Cycles 2 to 8: 56 mg/m2 per dose on Days 1, 8, and 15.
Arm group label:
Iber-KDd Combination Therapy
Intervention type:
Drug
Intervention name:
Daratumumab
Description:
Participants will receive Daratumumab (D) therapy subcutaneously (SC) or intravenously
(IV) as follows:
- Cycles 1 and 2: 1800 mg SC or 16 mg/kg IV on Days 1, 8, 15, and 22
- Cycles 3 through 6: 1800 mg SC or 16 mg/kg IV on Days 1 and 15
- Cycles 7 and 8: 1800 mg SC or 16 mg/kg IV on Day 1.
Arm group label:
Iber-KDd Combination Therapy
Intervention type:
Drug
Intervention name:
Dexamethasone
Description:
Participants will receive Dexamethasone (d) therapy either orally (PO) or intravenously
(IV) as follows:
- Cycles 1 and 2: 40 mg/dose on Days 1, 8, and 15; 20 mg/dose on Day 22
- Cycles 3 and 4: 40 mg/dose on Days 1, 8, and 15
- Cycles 5 through 8: 20 mg/dose on Days 1, 8, and 15.
Arm group label:
Iber-KDd Combination Therapy
Intervention type:
Drug
Intervention name:
Acetaminophen
Description:
Participants will receive Acetaminophen orally (PO) prior to Iber-KDd therapy as follows:
- Cycles 1 and 2: 650 mg/dose on Days 1, 8, 15, and 22
- Cycles 3 through 6: 650 mg/dose on Days 1 and 15
- Cycles 7 and 8: 650 mg/dose on Day 1.
Arm group label:
Iber-KDd Combination Therapy
Intervention type:
Drug
Intervention name:
Diphenhydramine
Description:
Participants will receive Diphenhydramine either orally (PO) or intravenously (IV) prior
to Iber-KDd therapy as follows:
- Cycles 1 and 2: 25 mg/dose on Days 1, 8, 15, and 22
- Cycles 3 through 6: 25 mg/dose on Days 1 and 15
- Cycles 7 and 8: 25 mg/dose on Day 1.
Arm group label:
Iber-KDd Combination Therapy
Intervention type:
Drug
Intervention name:
Montelukast
Description:
Participants will receive Montelukast orally (PO) prior to Iber-KDd as follows:
- Cycle 1 only: 10 mg/dose, Days 1, 8, 15, and 22, to be administered prior to the
first 4 doses of Daratumumab (D).
Arm group label:
Iber-KDd Combination Therapy
Summary:
The investigators want to find out whether or not giving patients who have relapsed or
refractory multiple myeloma (MM) the experimental medication combination iberdomide,
carfilzomib, daratumumab, and dexamethasone (Iber-KDd) may produce better results than
the current (standard of care) treatments. This study will examine the tolerability and
efficacy of this combination therapy for all participants and the ability of this
combination therapy to shrink or prevent MM from returning.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients with histologically confirmed MM with progressive disease according to the
IMWG criteria 47 during or within 60 days of their last regimen who have received
1-3 lines of prior therapy (inclusive of a lenalidomide-containing regimen) and have
measurable disease within 4 weeks of enrollment based on one of the following:
- Serum monoclonal protein ≥ 1.0 g/dL
- Urine monoclonal protein ≥ 200 mg/24 hour
- Involved serum immunoglobulin free light chains (FLC) ≥ 10 mg/dL AND abnormal
kappa/lambda ratio.
Note: Because the primary endpoint is MRD-negativity rate, per the discretion of the
Principal Investigator (PI), patients without measurable disease (e.g., M-spike <
1.0 g/dL) may also be enrolled in line with the IMWG MM response criteria 47.
2. Prior treatment with cluster of differentiation 38 (CD38) -directed therapy is
permitted only if all the following are fulfilled:
- Best response achieved during CD38-directed therapy was ≥ PR.
- Patient did not progress while receiving CD38-directed therapy or within 60
days of last dose of therapy.
- Patient did not discontinue CD38-directed therapy due to a related AE.
3. Prior treatment with carfilzomib is permitted only if all the following are
fulfilled:
- Best response achieved during carfilzomib-based therapy was ≥ PR.
- Patient did not progress while receiving carfilzomib-based therapy or within 60
days of last dose of therapy.
- Patient did not discontinue carfilzomib due to a related AE.
4. Creatinine Clearance (CrCl) ≥60 ml/min measured within 4 weeks of enrollment. CrCl
can be measured or estimated using Cockcroft-Gault method, Modification of Diet in
Renal Disease (MDRD), or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
formulae.
5. Age ≥ 18 years at the time of signing the informed consent documentation. Age limit
of 75 years.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 within 4 weeks of
enrollment (Appendix A).
7. Absolute neutrophil count (ANC) ≥ 1.0 K cells/µL, hemoglobin ≥ 8 g/dL, and platelet
count ≥ 50 K platelets/µL measured within 4 weeks of enrollment unless cytopenias
are deemed to be due to disease at the discretion of the clinical Investigator.
Transfusions and administration of growth factors are permissible.
8. Adequate hepatic function with bilirubin < 1.5 x the upper limit of normal (ULN) and
aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3.0 x ULN
measured within 4 weeks of enrollment.
9. All study participants must be able to tolerate one of the following
thromboprophylactic strategies: oral factor Xa inhibitors or low molecular weight
heparin or alternative anti-coagulant.
10. Females of childbearing potential (FCBP)† must have a negative serum or urine
pregnancy test within 10-14 days and again within 24 hours prior to prescribing of
iberdomide for Cycle 1 (prescriptions must be filled within 7 days) 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
(barrier) method, at the same time at least 28 days before she starts taking
iberdomide without interruption. 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.
- A FCBP is a female who: 1) has achieved menarche at some point, 2) has not
undergone a hysterectomy or bilateral oophorectomy, or 3) has not been
naturally postmenopausal (amenorrhea following cancer therapy does not rule out
childbearing potential) for at least 24 consecutive months (i.e., has had
menses at any time in the preceding 24 consecutive months). Females who do not
meet the above definition of FCBP should be classified as females not of
childbearing potential (FNCBP).
Exclusion Criteria:
1. Patients receiving concurrent systemic treatment for MM with the following
exceptions:
- Treatment of hypercalcemia or spinal cord compression or aggressively
progressing myeloma with current or prior corticosteroids is permitted.
- Patients may receive kyphoplasty/vertebroplasty for symptomatic vertebral
compression fractures.
- Bone targeting agents are permitted.
- Concurrent or prior treatment with corticosteroids for indications other than
MM is permitted.
- Focal radiation therapy within 14 days prior to randomization with the
exception of palliative radiotherapy for symptomatic management but not on
measurable extramedullary plasmacytoma.
- Prior MM treatments must be concluded with a washout period of 2 weeks from
last dose.
2. Patients who are refractory to an anti-CD38-directed regimen:
- Prior anti-CD38-directed therapy and carfilzomib are permitted as long as above
inclusion criteria are met.
3. Patients with plasma cell leukemia.
4. Patients with Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin
changes syndrome (POEMS syndrome).
5. Patients with amyloidosis.
6. Patients with known chronic obstructive pulmonary disease (COPD) with a forced
expiratory volume in 1 second (FEV1) < 50% of predicted normal within 4 weeks of
enrollment.
Note: FEV1 testing is required for patients suspected of having COPD, and patients
must be excluded if FEV1 < 50% of predicted normal at any time during the study.
7. Pregnant or lactating females. Because there is a potential risk for AEs in nursing
infants secondary to treatment of the mother with carfilzomib in combination with
iberdomide, pregnant or lactating females are excluded from study participation.
These potential risks may also apply to other agents used in this study.
8. Uncontrolled hypertension (ie, systolic blood pressure [BP] > 160 mmHg, diastolic BP
> 100 mmHg) or diabetes
9. Patients with active hepatitis B or C infection.
10. Patient is:
- Seropositive for human immunodeficiency virus (HIV) (Section 10.3.5.1) within 4
weeks of enrollment.
- Seropositive for hepatitis B (defined by a positive test for hepatitis B
surface antigen [HBsAg]) within 4 weeks of enrollment. Patients with resolved
infection (i.e., patients who are HBsAg negative but positive for antibodies to
hepatitis B core antigen (anti-HBc) and/or antibodies to hepatitis B surface
antigen [anti-HBs]) must be screened using real-time polymerase chain reaction
(RT-PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR
positive will be excluded. EXCEPTION: Patients with serologic findings
suggestive of HBV vaccination (anti-HBs positivity as the only serologic
marker) AND a known history of prior HBV vaccination do not need to be tested
for HBV DNA by PCR.
- Seropositive for hepatitis C (except in the setting of a sustained virologic
response (SVR), defined as aviremia at least 12 weeks after completion of
antiviral therapy).
For more information regarding the timing and frequency of hepatitis testing, refer
to Section 10.3.5.1.
11. Significant cardiovascular disease with New York Heart Association (NYHA) class III
or IV symptoms, symptomatic ischemia, current uncontrolled arrhythmias, screening
electrocardiogram (ECG) with corrected QT interval (QTc) of > 470 msec within 4
weeks of enrollment, pericardial disease, or myocardial infarction within 4 months
prior to enrollment, and left ventricular ejection fraction (EF) < 40% as assessed
by transthoracic echocardiogram (ECHO) within 4 weeks of enrollment. Current
unstable angina as determined by history and physical exam, hypertrophic
cardiomyopathy or restrictive cardiomyopathy
12. Pulmonary hypertension
13. Has refractory gastrointestinal (GI) disease with refractory nausea/vomiting,
inflammatory bowel disease, or bowel resection that would prevent absorption of oral
agents
14. Uncontrolled intercurrent illness including but not limited to active infection or
psychiatric illness/social situations that would compromise compliance with study
requirements
15. Significant neuropathy ≥ Grade 3 with pain at baseline
16. Contraindication to any concomitant medication, including antivirals or
anticoagulation
17. Major surgery within 3 weeks prior to first dose
18. Prior treatment with iberdomide
19. For female patients: Patient plans to become pregnant or donate eggs during the
Treatment Period and/or required period for contraception use post-last dose of
study treatment.
20. For male patients: Patient plans to father a child or donate sperm during the
Treatment Period and/or required period for contraception use post-last dose of
study treatment.
21. Patients with limited decision-making capacity.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Miami
Address:
City:
Miami
Zip:
33136
Country:
United States
Status:
Recruiting
Contact:
Last name:
Michelle D Armogan
Phone:
305-243-7479
Email:
mda182@med.miami.edu
Investigator:
Last name:
Carl O Landgren, MD, PhD
Email:
Principal Investigator
Investigator:
Last name:
Benjamin Diamond, MD
Email:
Principal Investigator
Start date:
February 20, 2024
Completion date:
March 1, 2031
Lead sponsor:
Agency:
Carl Ola Landgren, MD, PhD
Agency class:
Other
Collaborator:
Agency:
Bristol-Myers Squibb
Agency class:
Industry
Source:
University of Miami
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05896228
