A Study of Carfilzomib, Lenalidomide, Dexamethasone and Daratumumab for Patients With Relapsed/Refractory Myeloma With Salvage Autologous Hematopoietic Cell Transplantation

NCT03556332 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 17-493
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 12

Brief Summary

The purpose of this study is to test any good and bad effects of giving a combination of study drugs before and after autologous stem cell transplant.

Conditions

Multiple Myeloma

Keywords

Carfilzomib; Lenalidomide; Dexamethasone; Daratumumab; salvage autologous hematopoietic cell transplantation; 17-493

Outcome Measures

Primary Outcomes (1)

• number of patients with complete remission (CR) rate

  Traditional Response Criteria from International Myeloma Working Group Criteria for Multiple Myeloma

  3 years

Study Arms (1)

Carfilzomib, Lenalidomide, Dexamethasone and Daratumumab & HCT

EXPERIMENTAL

After receiving four 28-day cycles of Dara-CRd, eligible patients will then undergo HCT with high dose melphalan conditioning. Sixty to ninety days after HCT, patients will receive another 4 cycles of Dara-CRd.

Drug: Carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone; Drug: Daratumumab; Procedure: autologous hematopoietic cell transplantation

Interventions

Carfilzomib DRUG

Dara-CRd Induction Cycle 1 ONLY: Carfilzomib 20 mg/m2 per dose, days 1 and 2; Carfilzomib 27 mg/m2 per dose, days 8, 9, 15, and 16 Cycles 2-4: Carfilzomib 27 mg/m2 per dose, days 1, 2, 8, 9, 15, and 16 Dara-CRd Consolidation (60-90 days post HCT) Cycles 5-8: Carfilzomib 27 mg/m2 per dose, days 1, 2, 8, 9, 15, and 16

Carfilzomib, Lenalidomide, Dexamethasone and Daratumumab & HCT

Lenalidomide DRUG

Dara-CRd Induction Cycles 1-4: Lenalidomide 25 mg/day, days 1-21 every 28 days Dara-CRd Consolidation (60-90 days post HCT) Cycles 5-8: Lenalidomide 25 mg/day, days 1-21 every 28 days

Carfilzomib, Lenalidomide, Dexamethasone and Daratumumab & HCT

Dexamethasone DRUG

Dara-CRd Induction Cycles 1-4: Dexamethasone 20 mg/dose, days 1, 2, 8, 9, 15, 16, 22, 23 Dara-CRd Consolidation (60-90 days post HCT) Cycles 5-8: Dexamethasone 20 mg/dose, days 1, 2, 8, 9, 15, 16, 22, 23

Carfilzomib, Lenalidomide, Dexamethasone and Daratumumab & HCT

Daratumumab DRUG

Dara-CRd Induction Cycles 1 and 2: Daratumumab 16 mg/kg weekly (days 1,8, 15, 22) Dara-CRd Consolidation (60-90 days post HCT) Cycles 3 and 4: Daratumumab 16 mg/kg every other week, days 1 and 15. Cycles 5-6:Daratumumab 16 mg/kg every other week, days 1 and 15. Schedule together with Carfilzomib and use scheduled dexamethasone as premed. Cycles 7-8: Daratumumab 16 mg/kg days 1 of each cycle.

Carfilzomib, Lenalidomide, Dexamethasone and Daratumumab & HCT

autologous hematopoietic cell transplantation PROCEDURE

High Dose Melphalan and Autologous Hematopoietic Cell Transplantation Patients will receive Melphalan 200 mg/m2 per institutional guidelines, or if over 70 years of age or creatinine \>2mg/dL, they will receive 140 mg/m2.

Carfilzomib, Lenalidomide, Dexamethasone and Daratumumab & HCT

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must be capable, willing, and able to provide written, informed consent.
• Age ≥ 18-years-old and \<= 75-years-old.
• Histologic confirmation of multiple myeloma by the enrolling institution
• Symptomatic myeloma that has progressed/relapsed after 1 to 3 prior lines of therapy
• Patients who have received \<=1 cycle of therapy after most recent progression/relapse are eligible to enroll on study
• 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
• Patients with measurable disease who received up to one cycle of any therapy within 60 days with a washout period of 4 weeks from last dose (on a trial or outside a trial) are eligible
• Maintenance single agent imid (ie. lenalidomide or pomalidomide) or monoclonal antibody (ie. daratumumab) do not require the 4-week washout period
• More than 2 x 10\^6 autologous CD34+ cells/kg cryopreserved. The graft may not be CD34+ selected or otherwise manipulated to remove tumor or other cells. The graft can be collected at the transplanting institution or by a referring center.
• Planning to receive autologous HCT per institutional standards as part of standard of care. Eligibility for autologous HCT should be based on institutional guidelines.
• However, at minimum all patients must meet the following criteria:
• KPS greater than 70

You may not qualify if:

• Plasma cell leukemia (\>20% circulating plasma cells) during screening studies
• POEMS syndrome
• 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
• Patients with HBV core antibody positive, but HBV PCR negative are eligible if they are on medication for suppression of HBV reactivation
• Patients with HCV antibody positive, but PCR negative are eligible.
• Serologically positive HIV (testing required during screening)
• Significant cardiovascular disease with NYHA Class III or IV symptoms, EF\<40% or hypertrophic cardiomyopathy, or restrictive cardiomyopathy, or myocardial infarction within 6 months prior to enrollment, or unstable angina, or unstable arrhythmia as determined by history and physical examination. Echocardiogram will be performed during screening evaluation.
• Moderate or severe pulmonary hypertension defined as PASP \>50 mm Hg
• Chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) \< 50% of predicted normal. Note that FEV1 testing is required for participants suspected of having COPD and participants must be excluded if FEV1 is \< 50% of predicted normal.
• Moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification. Note that participants who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate.
• Refractory GI disease that would prevent absorption of oral agents
• Uncontrolled intercurrent illness including but not limited to active infection or psychiatric illness/social situations that would compromise compliance with study requirements
• Significant neuropathy ≥Grade 3 or Grade 2 neuropathy with pain at baseline

Sponsors & Collaborators

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

Study Sites (12)

University of Alabama Comprehensive Cancer Center

Birmingham, Alabama, 35294, United States

Location

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

Location

Northwell Health

Manhasset, New York, 11030, United States

Location

New York University

New York, New York, 10010, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

Location

Wake Forest University (Data Collection Only)

Winston-Salem, North Carolina, 27109, United States

Location

Medical College of Wisconsin (Data Collection Only)

Milwaukee, Wisconsin, 53226, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

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

Study Officials

• Gunjan Shah, MD

  Memorial Sloan Kettering Cancer Center

  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

Model Details: Single arm, Simon two-stage phase II trial of combination therapy

Study Record Dates

• First Submitted: June 1, 2018
• First Posted: June 14, 2018
• Study Start: July 2, 2018
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: May 5, 2026

Record last verified: 2026-04

Locations

US (12)