Daratumumab, Carfilzomib, Lenalidomide and Low Dose Dexamethasone (DKRd) in Newly Diagnosed, Multiple Myeloma

NCT03500445 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: IRB17-1097
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine response rate after 8 cycles of D-KRd (daratumumab, carfilzomib, lenalidomide (Revlimid) and dexamethasone in patients with multiple myeloma.

Conditions

Myeloma; Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Rate of stringent complete response (sCR)

  8 months

• Rate of minimal residual disease (MRD)-negative disease as assessed by Next Generation Sequencing

  8 months

Secondary Outcomes (7)

• Long term rate of MRD-negative disease

  2 years

• Duration of response

  1 year

• Rate of progression free survival

  2 years

• Time to progression

  2 years

• Overall survival rate

  2 years

Study Arms (1)

Treatment Arm (D-KRd)

EXPERIMENTAL

Drug: Daratumumab; Drug: Carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Daratumumab DRUG

Daratumumab (16 mg/kg) will be administered as an IV infusion: * Cycle 1-2: 16 mg/kg weekly * Cycles 3-8: 16 mg/kg IV infusion every 2 weeks * Cycles 9-24: 16 mg/kg IV infusion Day 1

Also known as: DARZALEX®

Treatment Arm (D-KRd)

Carfilzomib DRUG

Carfilzomib will be given as an IV infusion over 30 minutes: * Cycle 1: 20 mg/m2 Days 1, 2; 36 mg/m2 Days 8, 9, 15, 16. Alternatively, intermediate dose escalation (to 27mg/m2 on days 8, 9 of cycle 1) will be allowed at the treating physician's discretion. * Cycle 2-9: 36 mg/m2 (or best tolerated dose) Days 1, 2, 8, 9, 15 and 16 * Cycles 9-24: 36 mg/m2 (or best tolerated dose) Days 1, 2, 15 and 16

Also known as: KYPROLIS®

Treatment Arm (D-KRd)

Lenalidomide DRUG

Lenalidomide will be taken orally as follows: • Cycles 1-24: 25 mg (or best tolerated dose) PO Days 1-21

Also known as: REVLIMID®

Treatment Arm (D-KRd)

Dexamethasone DRUG

Dexamethasone will be administered prior to carfilzomib (on days that they coincide), as follows: * Cycles 1-9: 40 mg PO (subjects ≤ 75 years) or 20 mg PO (subjects ≥ 75 years) per week * Cycles 9-24: 20 mg PO per week 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

Treatment Arm (D-KRd)

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Chicago: lead
• Janssen Scientific Affairs, LLC: collaborator
• Amgen: collaborator

Study Sites (1)

The University of Chicago

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Neoplasms, Plasma Cell; Multiple Myeloma

Interventions

daratumumab; carfilzomib; Lenalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

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

Study Officials

• Benjamin Derman, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

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: April 9, 2018
• First Posted: April 18, 2018
• Study Start: February 13, 2019
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

US (1)