AzTrials
AzTrials

Multiple MyelomaPhase 2NCT04113018

Study of Daratumumab Combined With Carfilzomib, Lenalidomide and Dexamethasone for Newly Diagnosed Multiple Myeloma

A Phase 2 study testing Carfilzomib, lenalidomide, dexamethasone (KRd) + Daratumumab in people with Multiple Myeloma, run by Wake Forest University Health Sciences at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This study is being done because, despite major advances in therapy, MM is still considered an incurable disease. The purpose of this study is to determine the efficacy (how well it works) of the study treatment that combines the following drugs: daratumumab, carfilzomib, lenalidomide, dexamethasone in subjects who… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
Carfilzomib, lenalidomide, dexamethasone (KRd) + Daratumumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39 participants
Where
1 siteUnited States
Study dates
10 Jan 2020to Oct 2027
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subject must meet all of the following applicable inclusion criteria to participate in this study:
  • Written informed consent and HIPAA authorization for release of personal health information signed by the subject or his/her legally authorized representative. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
  • Age ≥ 18 years at the time of consent.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 (see Appendix A, Section 18.1) within 28 days prior to day 1 of treatment.
  • Confirmation of newly diagnosed multiple myeloma (NDMM) as per the IMWG 2014 criteria (see Appendix D, Section 18.4). Newly diagnosed MM patients who may have deferred transplant are also allowed.
  • Measurable disease present at baseline assessments. Baseline disease assessments are defined as disease assessments collected within 28 days of initiation of the first pre-study induction cycle (subjects who received prior therapy) or within 28 days prior to day 1 of study treatment (subjects with no prior therapy). Measurable disease is defined as:
Show all 44Show fewer
  • Serum M-protein ≥ 1 g/dL (> 0.5 g/dL for IgA or IgM) OR
  • Urine M-protein ≥ 200 mg/24 h OR
  • Involved free light chain (FLC) level ≥ 10 mg/dL provided serum FLC ratio is abnormal
  • No more than one prior cycle of systemic therapy (completed within 6 weeks of consent) for MM (to accommodate subjects who needed emergent therapy at diagnosis); any prior radiotherapy must be completed at least 14 days prior to day 1 of treatment. Subject must have recovered from treatment-induced toxicities to ≤ grade 1 or baseline.
  • Demonstrate adequate organ function within 1 week of day 1 of treatment as defined in the table below:
  • Hematological:
  • White Blood Cell (WBC) : ≥ 2,000/mm3
  • Absolute Neutrophil Count (ANC) : ≥ 1,000/mm3 without growth factors within 1 week of day 1 of treatment
  • Hemoglobin (Hgb) : ≥ 8 g/dL
  • Platelet count : ≥ 70,000/mm3 if bone marrow plasmacytosis of <50%; otherwise ≥ 50,000/mm3
  • Renal:
  • Serum creatinine with Creatinine clearance : ≤ 1.5 × upper limit of normal (ULN) with creatinine clearance
  • ≥ 30 mL/min as measured by a 24-hour urine collection or estimated by the Cockcroft - Gault formula ( See formula in Appendix B, Section 18.2 )
  • Hepatic:
  • Bilirubin : ≤ 2 × ULN; < 3.0 for subjects with Gilbert's Syndrome
  • Aspartate aminotransferase (AST) : ≤ 2.5× ULN
  • Alanine aminotransferase (ALT) : ≤ 2.5 × ULN
  • Adequate cardiac function as defined by ≥ 45% Left Ventricular Ejection Fraction (LVEF) by ECHO or MUGA within 28 days prior to day 1 of treatment.
  • Females of childbearing potential (FCBP) must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to day 1 of treatment, and be willing to undergo serial serum or urine pregnancy testing. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are postmenopausal (at least 12 consecutive months with no menses without an alternative medical cause).
  • FCBP must be willing to use a highly effective contraceptive method (i.e., achieves a failure rate of <1% per year when used consistently and correctly) plus a second contraceptive method (considered acceptable [failure rate of >1% per year] or highly effective) from the time of informed consent until 3 months after the last protocol prescribed therapy (which also includes FCBP on carfilzomib) has been discontinued. NOTE: estrogens may further increase the risk of thrombosis (beyond that associated with lenalidomide) and their use should be based on a benefit-risk decision. For the highly effective contraceptive method, a method with low user dependency is preferable but not required (see tables, adapted from: http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf)
  • Highly Effective Birth Control Methods:
  • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation
  • oral
  • intravaginal
  • transdermal
  • progestogen-only hormonal contraception associated with inhibition of ovulation
  • oral
  • injectable
  • implantable (Contraception method considered to have low user dependency)
  • intrauterine devide (IUD) (Contraception method considered to have low user dependency)
  • intrauterine hormone-releasing system (IUS) (Contraception method considered to have low user dependency)
  • vasectomised partner (Contraception method considered to have low user dependency) Vasectomised partner is a highly effective birth control method provided that partner is the sole sexual partner of the FCBP trial participant
  • sexual abstinence (Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments)
  • Acceptable Birth Control Methods:
  • Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action
  • Male or female condom with or without spermicide (A combination of male condom with either cap, diaphragm or sponge with spermicide (double barrier methods) are also considered acceptable, but not highly effective, birth control methods.
  • Male subjects (even those who have had a vasectomy) who are sexually active with a FCBP must be willing to use latex or synthetic condoms from initiation of study treatment until 3 months after the last protocol prescribed therapy has been discontinued. They must also refrain from donating sperm for at least 90 days after the last dose of carfilzomib and at least 90 days from the last dose of daratumumab. The FCBP partner should also consider contraception recommendations (see inclusion #10).
  • As determined by the enrolling physician, ability of the subject to understand and comply with study procedures for the entire length of the study.

Who cannot join

  • Subjects meeting any of the criteria below may not participate in the study:
  • Any infection requiring systemic therapy (i.e. involving IV antibiotics) (NOTE: at discretion of investigator, subjects with uncomplicated urinary tract infections may be eligible).
  • Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study, and any female subject must agree not to donate eggs during the study and for 3 months after the last protocol prescribed therapy has been discontinued).
  • Has a known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, carcinoma of the prostate with a current PSA value of <0.5 ng/mL or other cancer for which the subject has completed treatment, been disease-free for at least five years, and is considered by Sponsor-Investigator to be at <30% risk of relapse, or on hormonal therapy for a history of either prostate cancer or breast cancer, provided that there has been no evidence of disease progression during the previous three years.
  • Non-secretory MM.
  • Active involvement of the central nervous system by MM.
Show all 20Show fewer
  • Prior cardiovascular cerebrovascular accident with persistent neurological deficit.
  • Has chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) < 50% of predicted normal. FEV1 is required for subjects suspected of having chronic obstructive pulmonary disease and are not eligible if FEV1 is < 50% of predicted normal.
  • Has had moderate or severe persistent asthma within the past 2 years from enrollment and/or has currently uncontrolled asthma of any classification. Note that participants who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate.
  • POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
  • Had major surgery within 2 weeks prior to day 1 of treatment.
  • Exposure to any investigational drug (including investigational vaccine) or invasive investigational medical device within 4 weeks or 5 pharmacokinetic half-lives prior to day 1 of treatment, whichever is longer.
  • Uncontrolled clinically significant illness including, but not limited to, uncontrolled hypertension (as per the most updated Joint National Committee for the Management of Hypertension definitions), symptomatic congestive heart failure (as per New York Heart Association [NYHA] class III or IV [see Appendix C, Section 18.3], uncontrolled angina pectoris, myocardial infarction within the past 6 months from consent, known or suspected amyloidosis, uncontrolled cardiac arrhythmia, psychiatric illness/social situations that would limit compliance with study requirements as determined by the investigator, or any other condition (including laboratory abnormalities) that would, in the opinion of the investigator, place the subject at unacceptable risk if he/she were to participate in the study.
  • Known allergies, hypersensitivity or intolerance to monoclonal antibodies or human proteins, daratumumab +hyaluronidase or its excipients or known sensitivity to mammalian-derived products, carfilzomib or its excipients, lenalidomide or its excipients, or dexamethasone or its excipients.
  • Is seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (i.e. subjects 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) DNA levels. Those who are PCR positive will be excluded. Exception: subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of HBV vaccination do not need to be tested for HBV DNA by PCR.
  • Is 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). Subject is not required to have hepatitis C testing at screening.
  • Is known to be seropositive for human immunodeficiency virus.
  • Transplant ineligible subjects > 70 years old only: Defined frail, per IMWG criteria of 'frailty'. Frailty assessment does not need to be performed unless the subject is transplant ineligible and > 70 years old. "Frail" is defined as a frailty score of ≥ 2.
  • Prior or current exposure to daratumumab or other anti-CD-38 therapies.
  • Focal radiation therapy within 14 days prior to C1D1 with the exception of palliative radiotherapy for symptomatic management but not on measurable extramedullary plasmacytoma.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Levine Cancer Institute

    Charlotte, North Carolina, 28204

Other trials in United States

About this study

Official title: LCI-HEM-MYE-KRdD-001: Phase II Study of Daratumumab Combined With Carfilzomib, Lenalidomide and Dexamethasone in Newly Diagnosed Multiple Myeloma

This study is being done because, despite major advances in therapy, MM is still considered an incurable disease. The purpose of this study is to determine the efficacy (how well it works) of the study treatment that combines the following drugs: daratumumab, carfilzomib, lenalidomide, dexamethasone in subjects who have a recent diagnosis of multiple myeloma (MM). Normal plasma (blood) cells are found in the bone marrow and are an important part of the immune system. MM is a cancer formed by malignant (cancerous) plasma cells. Daratumumab, one of the study drugs, is a man-made protein that works with your immune system by attaching itself to the cancerous cells. Once daratumumab attaches itself to these cells, it gets your body's immune system to attack and destroy the MM cells. Daratumumab has shown to be effective in subjects with MM when combined with medicines like bortezomib, or lenalidomide + dexamethasone.

Read the detailed description

This single arm, two-stage, open-label Phase II study is designed with the primary objective of evaluating the efficacy of induction therapy comprised of 8 cycles of carfilzomib, lenalidomide, dexamethasone and daratumumab (KRd+daratumumab) in terms of complete response or better (CR) in subjects with NDMM, and comparing to relevant historical controls. Post induction, all subjects will undergo disease evaluation, including assessment of minimal residual disease (MRD). Post-induction disease evaluation will be followed by an MRD-based treatment algorithm. This trial will allow us to gather preliminary data on use of MRD status to direct post-induction therapy.

Being tested
Carfilzomib, lenalidomide, dexamethasone (KRd) + Daratumumab
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Carfilzomib, lenalidomide, dexamethasone (KRd) + DaratumumabDrug

    Experimental

Study groups in NCT04113018
Study groupRoleWhat they receive
KRd-DaratumumabExperimentalInduction: Carfilzomib, lenalidomide, dexamethasone (KRd) + Daratumumab
Receives: Drug: Carfilzomib, lenalidomide, dexamethasone (KRd) + Daratumumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Complete Response or Stringent Complete Response to Induction

    The primary endpoint is a binary variable determined for each subject indicating whether the subject achieved a complete response (CR) or stringent complete response (sCR) to induction treatment with KRd-Dara, as defined by the IMWG 2016 response criteria. Per IMWG 2016 criteria, CR is defined as negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow aspirates. sCR is defined as CR plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry.

    Measured: From enrollment to best response determined at the end of induction (8 28-day cycles); the median length of induction was 32 weeks

Secondary outcomes (6)

  1. Number of Participants With an Objective Response (OR)

    Objective response is determined for each subject as a binary variable indicating whether or not the subject achieved a best overall response of stringent complete response (sCR), complete response (CR) or partial response (PR) as determined by IMWG 2016 response criteria.

    Measured: From enrollment to best response while on study treatment; subjects remained on treatment until disease progression or death or unacceptable toxicity; assessed for approximately 5 years

  2. Overall Survival (OS)

    OS is defined as the duration from enrollment to the study (treatment start date) to the date of death from any cause. Participants who are alive or lost to follow-up at the time of the analysis will be censored at the last known date they were alive.

    Measured: From date of treatment start to date of death, or censored as described; assessed for approximately 5 years

  3. Progression Free Survival (PFS)

    PFS is defined as the duration of time from treatment start date to first occurrence of either progressive disease (PD) or death. PD must be objectively determined per IMWG 2016 criteria, where progression date is date of last assessment that identified PD. If subject died without documented PD, progression date will be death date. For surviving subjects who do not have PD, PFS will be censored at the date of last disease assessment. For subjects who received subsequent anti-cancer therapy prior to documented PD, PFS will be censored at the date of last disease assessment prior to commencement of subsequent therapy. Subjects who have an initial PFS event immediately following 2 or more consecutive missed assessments will be censored at date of last assessment prior to missed assessments.

    Measured: From date of treatment start to date of progression or death, or censored as described; assessed for approximately 5 years

  4. Time to Disease Progression (TTP)

    TTP is defined as the duration of time from treatment start date to first occurrence of either progressive disease (PD) or death related to disease progression. PD must be objectively determined per IMWG 2016 criteria, where progression date is date of last assessment that identified PD. If a subject died for causes related to disease progression then progression date will be date of death. If a subject died for causes other than disease progression, TTP will be censored at the date of other cause mortality. For surviving subjects who do not have PD, TTP will be censored at the date of last disease assessment. For subjects who received subsequent anti-cancer therapy prior to documented PD, TTP will be censored at the date of last disease assessment prior to commencement of subsequent therapy. Subjects who have an initial TTP event immediately following 2 or more consecutive missed assessments will be censored at date of last assessment prior to missed assessments.

    Measured: From date of start of treatment to date of disease progression or death, or censored as described; assessed for approximately 5 years

  5. Duration of Response (DoR)

    Duration of response (DoR) will be calculated for each subject achieving a PR or better and will be calculated from the time of the first assessment that identified response until disease progression or death. The censoring mechanism will be the same as described for PFS.

    Measured: From date of first response to date of progression or death, or censored as described; assessed for approximately 5 years

  6. Time to Next Treatment (TTNT)

    Time to next treatment (TTNT) will be calculated from the time of treatment start until the start of the first subsequent anti-cancer therapy after all protocol directed therapy is completed. For surviving subjects who do not receive subsequent therapy, TTNT will be censored at the last contact date. For subjects who die before beginning subsequent anti-cancer therapy, TTNT will be censored at the date of death.

    Measured: From treatment start date to date of next treatment, or censored as described; assessed for approximately 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Oct 2019
  2. Study start10 Jan 2020
  3. Primary completion28 Jun 2023
  4. Study completionOct 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
39 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04113018
Sponsor's protocol ID
IRB00081541
Other IDs
00037709, LCI-HEM-MYE-KRDD-001
Status last verified
Jul 2026
First submitted
27 Sep 2019
Last updated
13 Aug 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Bhutani M, Robinson M, Foureau D, Atrash S, Paul B, Guo F, Grayson JM, Ivanina-Foureau A, Pineda-Roman M, Varga C, Friend R, Ferreri CJ, Begic X, Norek S, Drennan T, Anderson MB, Symanowski JT, Voorhees PM, Usmani SZ. MRD-driven phase 2 study of daratumumab, carfilzomib, lenalidomide, and dexamethasone in newly diagnosed multiple myeloma. Blood Adv. 2025 Feb 11;9(3):507-519. doi: 10.1182/bloodadvances.2024014417.

    PubMed 39576965

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Carfilzomib, lenalidomide, dexamethasone (KRd) + Daratumumab in people with Multiple Myeloma, run by Wake Forest University Health Sciences at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 44 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 13 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Complete Response or Stringent Complete Response to Induction (time frame: From enrollment to best response determined at the end of induction (8 28-day cycles); the median length of induction was 32 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04113018, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in