Daratumumab, Carfilzomib, Lenalidomide and Low Dose Dexamethasone (DKRd) in Newly Diagnosed, Multiple Myeloma
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT03500445 |
Recruitment Status :
Recruiting
First Posted : April 18, 2018
Last Update Posted : January 7, 2021
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Myeloma Multiple Myeloma | Drug: Daratumumab Drug: Carfilzomib Drug: Lenalidomide Drug: Dexamethasone | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 75 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Open-label, Single-arm, Phase 2 Study of Initial Treatment With Daratumumab (Darzalex), Carfilzomib (Kyprolis), Lenalidomide (Revlimid) and Low Dose Dexamethasone (DKRd) in Newly Diagnosed, Multiple Myeloma Requiring Systemic Chemotherapy |
Actual Study Start Date : | February 13, 2019 |
Estimated Primary Completion Date : | June 2021 |
Estimated Study Completion Date : | January 2023 |

Arm | Intervention/treatment |
---|---|
Experimental: Treatment Arm (D-KRd) |
Drug: Daratumumab
Daratumumab (16 mg/kg) will be administered as an IV infusion:
Other Name: DARZALEX® Drug: Carfilzomib Carfilzomib will be given as an IV infusion over 30 minutes:
Other Name: KYPROLIS® Drug: Lenalidomide Lenalidomide will be taken orally as follows: • Cycles 1-24: 25 mg (or best tolerated dose) PO Days 1-21 Other Name: REVLIMID® Drug: Dexamethasone Dexamethasone will be administered prior to carfilzomib (on days that they coincide), as follows:
During weeks when daratumumab is given: 40 mg dexamethasone weekly, 20 mg prior to daratumumab infusion and 20 mg PO the day after During weeks with no daratumumab, single dose of 20 mg on day 1 |
- Rate of stringent complete response (sCR) [ Time Frame: 8 months ]
- Rate of minimal residual disease (MRD)-negative disease as assessed by Next Generation Sequencing [ Time Frame: 8 months ]
- Long term rate of MRD-negative disease [ Time Frame: 2 years ]
- Duration of response [ Time Frame: 1 year ]
- Rate of progression free survival [ Time Frame: 2 years ]
- Time to progression [ Time Frame: 2 years ]
- Overall survival rate [ Time Frame: 2 years ]
- Overall response rate [ Time Frame: 2 years ]
- Number of grade 2 or higher side effects as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.0 criteria [ Time Frame: 8 months ]

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
-
Newly diagnosed, previously untreated myeloma requiring systemic chemotherapy
• Prior treatment of hypercalcemia or spinal cord compression or active and/or aggressively progressing myeloma with corticosteroids or lenalidomide or bortezomib-based regimens does not disqualify the patient (the treatment dose should not exceed the equivalent of 160 mg of dexamethasone in a 4 week period or not more than 1 cycle of Proteasome Inhibitor / Immunomodulatory-based therapy)
- Both transplant and non-transplant candidates are eligible.
- Diagnosis of symptomatic multiple myeloma as per current International Myeloma Working Group (IMWG) uniform criteria prior to initial treatment
- Monoclonal plasma cells in the Bone Marrow (BM) ≥ 10% or presence of a biopsy-proven plasmacytoma
-
Measurable disease, prior to initial treatment as indicated by one or more of the following:
- Serum M-protein ≥ 1 g/dL
- Urine M-protein ≥ 200 mg/24 hours
- If serum protein electrophoresis is felt to be unreliable for routine M-protein measurement, then quantitative immunoglobulin levels are acceptable
- Serum freelite measurable disease as per current IMWG criteria
- Bone marrow specimen will be required at study entry; available DNA sample from pre-induction BM will be used for calibration step for MRD evaluation by gene sequencing.
- Males and females ≥ 18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Adequate hepatic function, with bilirubin ≤ 1.5 x upper limit of normal (ULN) and aspirate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN
- Absolute Neutrophil Count (ANC) ≥ 1.0 x 109/L, hemoglobin ≥ 8 g/dL, platelet count ≥ 75 x 109/L.
- Calculated creatinine clearance (by Cockroft-Gault) ≥ 50 mL/min or serum creatinine below 2 g/dL
- Woman of childbearing potential must have 2 negative pregnancy tests prior to initiating lenalidomide.
- Woman of childbearing potential must agree to use 2 reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting lenalidomide; 2) while participating in the study; and 3) for at least 30 days after discontinuation from the study.
- Male subjects must agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 90 days following discontinuation from the study even if he has undergone a successful vasectomy.
- All study participants in the US must be consented to and registered into the mandatory Revlimid Risk Evaluation and Mitigation Strategy (REMS®) program and be willing and able to comply with the requirements of Revlimid REMS®.
- Voluntary written informed consent.
Exclusion Criteria:
- Frail non-transplant candidates, defined as in Palumbo et al, Blood 2015.
- Non-secretory or hyposecretory multiple myeloma, prior to initial treatment defined as <1.0 g/dL M-protein in serum, <200 mg/24 hr urine M-protein, and no measurable disease as per IMWG by Freelite.
- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Amyloidosis
- Plasma cell leukemia
- Waldenström's macroglobulinemia or Immunoglobulin M-producing (IgM) myeloma
- Radiotherapy to multiple sites or immunotherapy within 4 weeks before start of protocol treatment (localized radiotherapy to a single site at least 1 week before start is permissible)
- Participation in an investigational therapeutic study within 3 weeks or within 5 drug half-lives (t1/2) prior to first dose, whichever time is greater
- Potential subjects with evidence of progressive disease as per IMWG criteria
- Patients not able to tolerate daratumumab, carfilzomib, lenalidomide or dexamethasone
- Peripheral neuropathy ≥ Grade 2 at screening
- Diarrhea > Grade 1 in the absence of antidiarrheals
- Central Nervous System (CNS) involvement
- Pregnant or lactating females
- Major surgery within 3 weeks prior to first dose.
- Myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
- Prior or concurrent pulmonary embolism
-
Known moderate or severe persistent asthma or known chronic obstructive pulmonary disease (COPD)
- Known or suspected chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal
- Moderate or severe persistent asthma within the past 2 years, or currently has uncontrolled asthma of any classification. Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study.
- Rate-corrected QT interval of electrocardiograph (QTc) > 470 msec on a 12-lead ECG during screening
- Uncontrolled hypertension or diabetes
- Acute infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose
- Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible.
- Non-hematologic malignancy or non-myeloma hematologic malignancy within the past 3 years except a) adequately treated basal cell, squamous cell skin cancer, thyroid cancer, carcinoma in situ of the cervix, or prostate cancer < Gleason Grade 6 with stable prostate specific antigen levels or cancer considered cured by surgical resection alone
- Any clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03500445
United States, Illinois | |
The University of Chicago | Recruiting |
Chicago, Illinois, United States, 60637 | |
Contact: Amanda McIver 773-834-5884 amciver@medicine.bsd.uchicago.edu | |
Principal Investigator: Andrzej Jakubowiak, MD, PhD |
Principal Investigator: | Andrzej Jakubowiak, MD, PhD | University of Chicago |
Responsible Party: | University of Chicago |
ClinicalTrials.gov Identifier: | NCT03500445 |
Other Study ID Numbers: |
IRB17-1097 |
First Posted: | April 18, 2018 Key Record Dates |
Last Update Posted: | January 7, 2021 |
Last Verified: | January 2021 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Undecided |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases Dexamethasone |
Lenalidomide Daratumumab Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Antineoplastic Agents Immunologic Factors Angiogenesis Inhibitors |