A Study of Daratumumab in Patients With Newly Diagnosed Multiple Myeloma

NCT03290950 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 17-352
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 7

Brief Summary

This is a study to test the safety and effectiveness of the study drug, daratumumab in combination with carfilzomib, lenalidomide and dexamethasone. The purpose of this study is to test whether giving daratumumab along with the other drugs (carfilzomib, lenalidomide and dexamethasone) is safe for patients.

Conditions

Multiple Myeloma

Keywords

Daratumumab; Carfilzomib; Lenalidomide; Dexamethasone; 17-352

Outcome Measures

Primary Outcomes (1)

• assess the rate of MRD negativity

  Patients with ≤ PR after completing 4 cycles will be included in the analysis of the primary objective and will be considered MRD positive. Patients who receive any study drug and have at least one post-baseline disease assessment will be considered evaluable for the primary endpoint.

  2 years

Study Arms (2)

Cohort 1

EXPERIMENTAL

Single arm, two-stage phase II trial of combination therapy (daratumumab, carfilzomib, lenalidomide, and dexamethasone for newly diagnosed multiple myeloma patients. Patients achieving ≥PR at end of 4 cycles will continue to receive the planned total of 8 cycles of combination therapy. Patients may go onto receiving additional maintenance phase therapy with lenalidomide under a separate treatment protocol. Patients ≤ PR after completing 4 cycles will go off study therapy.

Drug: daratumumab; Drug: carfilzomib; Drug: lenalidomide; Drug: dexamethasone

Cohort 2

EXPERIMENTAL

Single arm, two-stage phase II trial of combination therapy (daratumumab, carfilzomib, lenalidomide, and dexamethasone for newly diagnosed multiple myeloma patients. Patients achieving ≥PR at end of 4 cycles will continue to receive the planned total of 8 cycles of combination therapy. Patients may go onto receiving additional maintenance phase therapy with lenalidomide under a separate treatment protocol. Patients ≤ PR after completing 4 cycles will go off study therapy.

Drug: daratumumab; Drug: carfilzomib; Drug: lenalidomide; Drug: dexamethasone

Interventions

daratumumab DRUG

Cycle 1 ONLY: Daratumumab 16 mg/kg days 1, 8, 15, and 22, Cycle 2: Daratumumab 16mg/kg days 1, 8, 15, and 22; Cycles 3-6: Daratumumab 16mg/kg days 1 and 15, Cycles 7-8: Daratumumab 16mg/kg day 1; Daratumumab rate of infusion is per MSKCC guidelines.

Cohort 1; Cohort 2

carfilzomib DRUG

Cycle 1 ONLY: Carfilzomib 20 mg/m2 per dose, days 2 and 3; Carfilzomib 36 mg/m2 per dose, days 8, 9, 15, and 16; Cycles 2-8: Carfilzomib 36 mg/m2 per dose, days 1, 2, 8, 9, 15, and 16

Cohort 1; Cohort 2

lenalidomide DRUG

Cycle 1 ONLY: Lenalidomide 25 mg/day, days 2-21 every 28 days; Cycles 2-8: Lenalidomide 25 mg/day, days 1-21 every 28 days

Cohort 1; Cohort 2

dexamethasone DRUG

Cycle 1 ONLY: Dexamethasone 20 mg/dose, days 2, 3, 8, 9, 15, 16, Cycles 2: Dexamethasone 20mg/dose, days 1, 2, 8, 9, 15, 16 and 22; Cycles 3-4: Dexamethasone 20mg/dose, days 1,2,8,9,15 and 16, Cycles 5- 8: Dexamethasone 10mg/dose, days 1, 2, 8, 9, 15, and 16

Also known as: Cohort 1 administration

Cohort 1

Eligibility Criteria

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

You may qualify if:

• Newly diagnosed patients with histologically confirmed MM based on the following criteria:
• Clonal plasma cells in the bone marrow
• Measurable disease within the past 4 weeks defined by any one of the following:
• Serum monoclonal protein ≥ 1.0 g/dL
• Urine monoclonal protein \>200 mg/24 hour
• Involved serum immunoglobulin free light chain \> 10 mg/dL AND abnormal kappa/lambda ratio
• Evidence of underlying end organ damage and/or myeloma defining event attributed to underlying plasma cell proliferative disorder meeting at least one of the following:
• Hypercalcemia: serum calcium \>0.25 mmol/L (\> 1 mg/dL) above upper limit of normal or ≥ 2.75 mmol/L (11 mg/dL)
• Anemia: hemoglobin value \<10 g/dL or \> 2 g/dL below lower limit of normal
• Bone disease: ≥ 1 lytic lesions on skeletal X-ray, CT, or PET-CT. For patients with 1 lytic lesion, bone marrow should demonstrate ≥10% clonal plasma cells
• Clonal bone marrow plasma cell percentage ≥60%
• Involved/un-involved serum free light chain ratio ≥100 and involved free light chain \>100 mg/L.
• focal lesion on magnetic resonance imaging study (lesion must be \>5 mm) in size
• Creatinine Clearance ≥ 60 ml/min. CrCl can be measured or estimated using Cockcroft-Gault method, MDRD, or CKD-EPI formulae
• Age ≥ 18 years at the time of signing the informed consent documentation

You may not qualify if:

• Patients receiving \>1 cycle of prior treatment or concurrent systemic treatment for multiple myeloma
• Treatment of hypercalcemia or spinal cord compression or aggressively progressing myeloma with current or prior corticosteroids is permitted
• Bisphosphonates are permitted
• Concurrent or prior treatment with corticosteroids for indications other than multiple myeloma is permitted
• Prior treatment with radiotherapy is permitted
• Prior treatment for smoldering myeloma is permitted with a washout period of 2 weeks from last dose. Smoldering patients previously treated with carfilzomib are excluded.
• Patients with measurable disease who received up to one cycle of any therapy within 60 days with a washout period of 2 weeks from last dose (on a trial or outside a trial) are eligible
• Plasma cell leukemia
• POEMS syndrome
• Amyloidosis
• Has known chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) \<50% of predicted normal (note that FEV1 testing is required for subjects suspected of having chronic obstructive pulmonary disease and subjects must be excluded if FEV1 \<50% of predicted normal).
• Pregnant or lactating females. Because there is a potential risk for adverse events nursing infants secondary to treatment of the mother with carfilzomib in combination with lenalidomide. These potential risks may also apply to other agents used in this study.
• Uncontrolled hypertension or diabetes
• Active hepatitis B or C infection
• Subject is:

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Janssen Pharmaceuticals: collaborator

Study Sites (7)

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Related Publications (1)

• Maura F, Boyle EM, Coffey D, Maclachlan K, Gagler D, Diamond B, Ghamlouch H, Blaney P, Ziccheddu B, Cirrincione A, Chojnacka M, Wang Y, Siegel A, Hoffman JE, Kazandjian D, Hassoun H, Guzman E, Mailankody S, Shah UA, Tan C, Hultcrantz M, Scordo M, Shah GL, Landau H, Chung DJ, Giralt S, Zhang Y, Arbini A, Gao Q, Roshal M, Dogan A, Lesokhin AM, Davies FE, Usmani SZ, Korde N, Morgan GJ, Landgren O. Genomic and immune signatures predict clinical outcome in newly diagnosed multiple myeloma treated with immunotherapy regimens. Nat Cancer. 2023 Dec;4(12):1660-1674. doi: 10.1038/s43018-023-00657-1. Epub 2023 Nov 9.

  PMID: 37945755 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab; carfilzomib; Lenalidomide; Dexamethasone

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

Study Officials

• Neha Korde, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Phase II study and treated with 4-drug combination of daratumumab, carfilzomib, lenalidomide, and dexamethasone.

Study Record Dates

• First Submitted: September 20, 2017
• First Posted: September 25, 2017
• Study Start: September 25, 2017
• Primary Completion: May 21, 2025
• Study Completion (Estimated): September 1, 2026
• Last Updated: December 15, 2025

Record last verified: 2025-12

Locations

US (7)