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

NCT04113018 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 3 other identifiers: IRB0008154100037709LCI-HEM-MYE-KRDD-001
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (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.

  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)

• Number of Participants With an Objective Response (OR)

  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

• Overall Survival (OS)

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

• Progression Free Survival (PFS)

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

• Time to Disease Progression (TTP)

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

• Duration of Response (DoR)

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

Other Outcomes (8)

• Number of Participants With Grade 3 or Higher Treatment-related Cardiovascular or Pulmonary-related Adverse Events During Induction

  From enrollment to completion of induction; evaluated for approximately 32 weeks (8 28-day cycles).

• Number of Participants With Grade 5 Adverse Events During Induction

  From enrollment to completion of induction; evaluated for approximately 32 weeks (8 28-day cycles).

• Number of Participants With at Least One Serious Adverse Event

  From enrollment to 30 days following cessation of study treatment. Reasons for study treatment discontinuation include progression, toxicity, consent withdrawal, or investigator decision; assessed for approximately 5 years.

Study Arms (1)

KRd-Daratumumab

EXPERIMENTAL

Induction: Carfilzomib, lenalidomide, dexamethasone (KRd) + Daratumumab

Drug: Carfilzomib, lenalidomide, dexamethasone (KRd) + Daratumumab

Interventions

Carfilzomib, lenalidomide, dexamethasone (KRd) + Daratumumab DRUG

Experimental

KRd-Daratumumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• Amgen: collaborator
• Celgene: collaborator
• Janssen, LP: collaborator

Study Sites (1)

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Related Publications (1)

• 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.

  PMID: 39576965 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; Lenalidomide; Dexamethasone; daratumumab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Chair of Biostatistics Department
• Organization: Atrium Health Levine Cancer

james.symanowski@atriumhealth.org

9804422371

Study Officials

• Manisha Bhutani, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2019
• First Posted: October 2, 2019
• Study Start: January 10, 2020
• Primary Completion: June 28, 2023
• Study Completion (Estimated): October 1, 2027
• Last Updated: February 3, 2026
• Results First Posted: July 16, 2024

Record last verified: 2026-01

Locations

US (1)