NCT03871829 · REGISTRY CONDITION SEARCH

Daratumumab Retreatment in Participants With Multiple Myeloma Who Have Been Previously Treated With Daratumumab

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE2
Status at capture: TERMINATED
Registry last update: 2025-03-30

The purpose of this study is to compare the efficacy (rate of very good partial response \[VGPR\] or better as best response as defined by the International Myeloma Working Group \[IMWG\] criteria) of daratumumab subcutaneous (Dara-SC) in combination with carfilzomib and dexamethasone (Kd) with the efficacy of Kd in participants with relapsed refractory multiple myeloma who were previously exposed to daratumumab to evaluate daratumumab retreatment.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Percentage of Participants Achieving Very Good Partial Response (VGPR) or Better Response

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outcome · POSTED

Overall Response Rate (ORR)

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outcome · POSTED

Percentage of Participants Achieving Complete Response (CR) or Better

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outcome · POSTED

Progression Free Survival (PFS)

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Percentage of Participants With Negative Minimal Residual Disease (MRD)

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outcome · POSTED

Time to Next Treatment

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outcome · POSTED

Serum Concentrations of Daratumumab

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outcome · POSTED

Number of Participants With Anti-recombinant Human Hyaluronidase (rHuPH20) Antibodies

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outcome · POSTED

Number of Participants With Anti-Daratumumab Antibodies

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Evidence of a response (partial response or better based on investigator's determination of response by International Myeloma Working Group \[IMWG\] criteria) to daratumumab-containing therapy with response duration of at least 4 months * Participants must have progressed from or be refractory to their last line of treatment. Relapsed or refractory disease as defined as: a) Relapsed disease is defined as an initial response to previous treatment, followed by confirmed progressive disease (PD) by IMWG criteria greater than (\>) 60 days after cessation of treatment. b) Refractory disease is defined as less than (\<) 25 percent (%) reduction in M-protein or confirmed PD by IMWG criteria during previous treatment or \>60 days after cessation of treatment * Received 1 to 3 prior line(s) of treatment of which one contained daratumumab, and completed daratumumab at least 3 months prior to randomization. A single line of therapy may consist of 1 or more agents, and may include induction, hematopoietic stem cell transplantation, and maintenance therapy. Radiotherapy, bisphosphonate, or a single short course of corticosteroids (no more than the equivalent of dexamethasone 40 milligram per day \[mg/day\] for 4 days) would not be considered prior lines of therapy * Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2 * Women of childbearing potential must have a negative urine or serum pregnancy test at screening within 14 days prior to randomization Exclusion Criteria: * Previous treatment with daratumumab within the last 3 months prior to randomization * Discontinuation of daratumumab due to a daratumumab-related adverse event (AE) * History of malignancy (other than multiple myeloma) unless all treatment of that malignancy was completed at least 2 years before consent and the patient has no evidence of disease. Further exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or breast, or other non-invasive lesion, that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years * Allergies, hypersensitivity, or intolerance to daratumumab, hyaluronidase, monoclonal antibodies (mAbs), human proteins, or their excipients, or known sensitivity to mammalian-derived products. Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib) * Participant is: a) Known to be seropositive for human immunodeficiency virus (HIV) with one or more of the following: not receiving highly active antiretroviral therapy (ART), had a change in ART within 6 months of the start of screening, receiving ART that may interfere with study treatment, cluster of differentiation (CD)4 count \<350 (unit: cells per cubic millimeter of blood) at screening, acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 6 months of start of screening, and not agreeing to start ART and be on ART \>4 weeks plus having HIV viral load \<400 copies/milliliters (mL) at end of 4-week period (to ensure ART is tolerated and HIV controlled. b) Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Participants with resolved infection (example: participants 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 (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded. c) Known to be 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)
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Participants will receive carfilzomib 20 milligram per square meter (mg/m\^2) intravenously (IV) on Day 1 of Cycle 1 and then 70 mg/m\^2 on Days 8 and 15 of Cycle 1 and thereafter on Days 1, 8, 15 of Cycle 2 onwards. Participants will receive dexamethasone 20 mg on Cycle 1 Day 1, a second dose of 20 milligram (mg) will be given on Cycle 1 Day 2 and 40 mg IV or orally on Days 8, 15, 22 for Cycle 1. Patients will then receive dexamethasone 40mg on days 1, 8, 15 and 22 for cycles 2-9, then on Days 1, 8, 15 for Cycle 10 onwards, until death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study. The total duration of each cycle is 28 Days.
intervention Names
Drug: Carfilzomib 20 mg/m^2
Drug: Carfilzomib 70 mg/m^2
Drug: Dexamethasone 40 mg
Drug: Dexamethasone 20 mg
label
Arm A: Carfilzomib+Dexamethasone (Kd)
type
ACTIVE_COMPARATOR
description
Participants will receive daratumumab subcutaneous (Dara-SC) 1800 mg by SC injection on Days 1, 8, 15, 22 for Cycle 1 and 2, Days 1 and 15 for Cycle 3-6, Day 1 for Cycle 7 onwards. Participants will receive carfilzomib 20 mg/m\^2 IV on Cycle 1 Day 1 and then 70 mg/m\^2 on Day 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2. Participants will receive dexamethasone 20 mg on Cycle 1 Day 1, a second dose of 20 milligram (mg) will be given on Cycle 1 Day 2 and 40 mg IV or orally on Days 8, 15, 22 for Cycle 1. Patients will then receive dexamethasone 40mg on days 1, 8, 15 and 22 for cycles 2-9, then on Days 1, 8, 15 for Cycle 10 onwards, until death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study. The total duration of each cycle is 28 Days.
intervention Names
Drug: Carfilzomib 20 mg/m^2
Drug: Carfilzomib 70 mg/m^2
Drug: Dexamethasone 40 mg
Drug: Dara-SC 1800 mg
Drug: Dexamethasone 20 mg
label
Arm B: Dara-SC in combination with Kd (DKd)
type
EXPERIMENTAL

interventions

arm Group Labels
Arm A: Carfilzomib+Dexamethasone (Kd)
Arm B: Dara-SC in combination with Kd (DKd)
description
Carfilzomib 20 mg/m\^2 will be administered intravenously (IV).
name
Carfilzomib 20 mg/m^2
type
DRUG
arm Group Labels
Arm A: Carfilzomib+Dexamethasone (Kd)
Arm B: Dara-SC in combination with Kd (DKd)
description
Carfilzomib 70 mg/m\^2 will be administered IV.
name
Carfilzomib 70 mg/m^2
type
DRUG
arm Group Labels
Arm A: Carfilzomib+Dexamethasone (Kd)
Arm B: Dara-SC in combination with Kd (DKd)
description
Dexamethasone 40 mg will be administered as IV infusion or orally.
name
Dexamethasone 40 mg
type
DRUG
arm Group Labels
Arm B: Dara-SC in combination with Kd (DKd)
description
Dara-SC 1800 mg will be administered by SC injection.
name
Dara-SC 1800 mg
type
DRUG
arm Group Labels
Arm A: Carfilzomib+Dexamethasone (Kd)
Arm B: Dara-SC in combination with Kd (DKd)
description
Dexamethasone 20 mg will be administered as IV infusion or orally.
name
Dexamethasone 20 mg
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 88
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Percentage of participants achieving VGPR or better response were reported. VGPR or better rate was defined as the percentage of participants achieving VGPR, complete response (CR), or stringent complete response (sCR) in accordance with the International Myeloma Working Group (IMWG) criteria, during or after the study treatment but before the start of subsequent anti-myeloma therapy. IMWG criteria for VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis, or greater than or equal to (\>=) 90 percent (%) reduction in serum M-protein plus urine M-protein less than (\<) 100 milligram (mg)/24 hours; for CR: Negative immunofixation on the serum and urine, and Disappearance of any soft tissue plasmacytomas (PCs), and \<5% PCs in bone marrow; for sCR: CR plus normal free light chain (FLC) ratio, and Absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4- color flow cytometry.
measure
Percentage of Participants Achieving Very Good Partial Response (VGPR) or Better Response
time Frame
Up to 3 years and 4 months

secondary Outcomes

description
ORR was defined as the percentage of participants who achieved partial response (PR) or better responses based on the computerized algorithm, in accordance with the IMWG criteria, during or after the study treatment but before the start of subsequent anti-myeloma therapy. IMWG criteria for PR: greater than or equal to (\>=)50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>=90% or less than (\<)200 mg/24 hours; If the serum and urine M-protein were not measurable, a decrease of \>=50% in the difference between involved and uninvolved free light chain (FLC) levels was required in place of the M-protein criteria; If serum and urine M-protein were not measurable, and serum free light assay is also not measurable, \>=50% reduction in bone marrow plasma cells (PCs) was required in place of M-protein, provided baseline bone marrow plasma cell percentage was \>=30%; additionally, if present at baseline, \>=50% reduction in the size of soft tissue PCs was also required.
measure
Overall Response Rate (ORR)
time Frame
Up to 3 years and 7 months
description
Percentage of participants achieving CR or better were reported. CR or better rate was defined as the percentage of participants achieving CR or sCR based on the computerized algorithm, according to IMWG response criteria. IMWG criteria for CR: Negative immunofixation on the serum and urine, and Disappearance of any soft tissue plasmacytomas (PCs), and \<5% PCs in bone marrow.
measure
Percentage of Participants Achieving Complete Response (CR) or Better
time Frame
Up to 3 years and 7 months
description
PFS was defined as the duration from the date of randomization to either progressive disease (PD) or death, whichever comes first. IMWG criteria for PD: \>=25% from lowest response level in serum M-component (the absolute increase must be \>=0.5 gram per deciliter \[g/dL\]) and/or in urine M-component (the absolute increase must be \>=200 mg/24 hour); only in participants without measurable serum and urine M-protein levels: increase of \>=25% in the difference between involved and uninvolved free light chain levels and the absolute increase must be \>10 mg/dL. BMPC%: the absolute % must be \>=10%; definite increase in size of existing bone lesions or soft tissue plasmacytomas; definite development of new bone lesions or soft tissue plasmacytomas; development of hypercalcemia (corrected serum calcium \>11.5 milligrams per deciliter (mg/dL) or 2.65 millimoles per liter \[mmol/L\]) that can be attributed solely to PC proliferative disorder.
measure
Progression Free Survival (PFS)
time Frame
Up to 3 years and 7 months
description
OS was defined as the time from the date of randomization to the date of the participant's death due to any cause.
measure
Overall Survival (OS)
time Frame
Up to 3 years and 7 months
description
Percentage of participants with negative MRD were reported. MRD negativity rate, defined as the percentage of participants who had MRD negative status at 10\^-5 by bone marrow aspirate after the date of randomization and prior to PD or subsequent anti-myeloma therapy.
measure
Percentage of Participants With Negative Minimal Residual Disease (MRD)
time Frame
Up to 3 years and 7 months
description
Time to next treatment was defined as the time from randomization to the start of the next-line treatment.
measure
Time to Next Treatment
time Frame
Up to 3 years and 7 months
description
Serum concentrations of daratumumab were assessed. This outcome measure was planned to be analyzed for specified arm only.
measure
Serum Concentrations of Daratumumab
time Frame
Day 1 of Cycles 1, 3, and 7 (each cycle of 28 days) and Follow Up (post treatment Week 8; up to 30.3 months)
description
The incidence of anti-rHuPH20 antibodies were summarized for all participants who received at least one dose of Dara-SC and had appropriate plasma samples for detection of antibodies to rHuPH20 (at least 1 sample after the start of the first dose of Dara-SC). This outcome measure was planned to be analyzed for specified arm only.
measure
Number of Participants With Anti-recombinant Human Hyaluronidase (rHuPH20) Antibodies
time Frame
Up to end of study; up to 30.3 months
description
Number of participants who test positive for anti-daratumumab antibodies were reported. This outcome measure was planned to be analyzed for specified arm only.
measure
Number of Participants With Anti-Daratumumab Antibodies
time Frame
Up to end of study; up to 30.3 months

Full study description

brief Summary: The purpose of this study is to compare the efficacy (rate of very good partial response \[VGPR\] or better as best response as defined by the International Myeloma Working Group \[IMWG\] criteria) of daratumumab subcutaneous (Dara-SC) in combination with carfilzomib and dexamethasone (Kd) with the efficacy of Kd in participants with relapsed refractory multiple myeloma who were previously exposed to daratumumab to evaluate daratumumab retreatment.
detailed Description: For relapsed or refractory multiple myeloma, the treatment is determined on an individual basis. Common standard of care regimens use either a proteasome inhibitor (PI) or an immunomodulatory agent (IMiD) in combination with dexamethasone with or without a monoclonal antibody (mAb) such as daratumumab. After relapse from PIs or IMiDs, patients are often retreated with drugs that have same mechanism of action to which they have been sensitive. The disease becomes refractory and all effective treatment options are exhausted. Daratumumab is a human IgG1 mAb that binds with high affinity to unique epitope on cluster of differentiation 38 (CD38) and attacks tumor cells that overexpress CD38. Study is to determine the efficacy of Dara-SC in combination with carfilzomib and dexamethasone (DKd) in adult participants with relapsed refractory MM who had 1 to 3 prior line(s) of treatment including a line containing daratumumab to evaluate daratumumab retreatment. The MM treatment is determined on an individual basis where patient's age, prior therapy, bone marrow function, co-morbidities, patient preference and time to relapse are considered. Common standard of care regimens use either PI or an IMiD in combination with dexamethasone with or without a mAb. It is a targeted immunotherapy that attacks tumor cells that overexpress CD38, a transmembrane glycoprotein, in a variety of hematological malignancies including multiple myeloma. The study will be conducted in 3 phases: Screening (28 days), Treatment, and Follow-Up. Assessments like chest X-ray, spirometry test, electrocardiogram (ECG), will be performed during Screening phase. During the Treatment Phase, participants will be randomized to receive Kd or DKd. Efficacy assessments like bone marrow examination will be performed. Follow-up will continue until the end of study.

Source references

references

citation
Bahlis NJ, Zonder J, Karlin L, Plesner T, Paris L, Wrobel T, Hungria V, Besemer B, Crusoe E, Silkjaer T, Perrot A, Moreau P, Wu KL, Delimpasi S, Dimopoulos MA, Levin MD, Mangiacavalli S, Nnane I, Kim YJ, Krevvata M, Sha L, Wroblewski S, Tuozzo A, Carson R, Facon T. Subcutaneous daratumumab plus carfilzomib and dexamethasone (D-Kd) versus carfilzomib and dexamethasone (Kd) in patients with relapsed/refractory multiple myeloma who received previous daratumumab treatment: LYNX study. Leuk Lymphoma. 2025 Dec;66(14):2685-2696. doi: 10.1080/10428194.2025.2561117. Epub 2025 Oct 3.
pmid
41041907
type
DERIVED

Source notices and limitations

Discovery and provenance

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Preserved source evidence · Not medical advice