Daratumumab, Carfilzomib, Pomalidomide, Dexamethasone In MM

NCT04176718 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 19-379
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 3

Brief Summary

This research study is studying the combination of daratumumab with weekly carfilzomib, pomalidomide, and dexamethasone in people with relapsed and refractory multiple myeloma. Relapsed and Refractory Multiple Myeloma is the condition of returned or previous treatment resistant Multiple Myeloma. This research study involves two study drugs and two standard of care drugs.

• The names of the study drugs involved in this study are:
• Carfilzomib
• Daratumumab
• The names of the standard of care drugs involved in this study are:
• Dexamethasone
• Pomalidomide

Conditions

Multiple Myeloma; Refractory Multiple Myeloma; Multiple Myeloma in Relapse; Relapse

Keywords

Multiple Myeloma; Refractory Multiple Myeloma; Multiple Myeloma in Relapse; Relapse

Outcome Measures

Primary Outcomes (2)

• Objective response rate of the daratumumab, carfilzomib, pomalidomide, and dexamethasone combination

  Simon's two-stage design will be used. An objective response rate of 40%

  28 Days

• Number of dose limiting toxicity grade 4 or higher treatment related

  28 Days

Secondary Outcomes (2)

• Progression-free survival (PFS)

  time from randomization to the disease progression or death from any cause up 60 months

• Rate of Minimal residual disease (MRD) negative status

  112 Days

Study Arms (1)

Daratumumab,Carfilzomib, Pomalidomide and Dexamethasone

EXPERIMENTAL

Patients who meet eligibility criteria for the study will subsequently be enrolled for treatment. Participants will receive daratumumab, carfilzomib, pomalidomide, and dexamethasone on a 28 day schedule. * Daratumumab will be given according to cycle and dosage determined by protocol. * Carfilzomib will be given at 56 mg/m2 on days 1, 8, 15 (except for C1D1 where it is 20 mg/m2) * Pomalidomide will be given daily on days 1-21. * Dexamethasone will be given weekly, split over two days.

Drug: Daratumumab; Drug: Carfilzomib; Drug: Pomalidomide; Drug: Dexamethasone

Interventions

Daratumumab DRUG

predetermined dose, intravenously, at predetermined times per cycle

Also known as: Darzalex

Daratumumab,Carfilzomib, Pomalidomide and Dexamethasone

Carfilzomib DRUG

predetermined dose, intravenously, give 3 times per cycle

Also known as: Kyprolis

Daratumumab,Carfilzomib, Pomalidomide and Dexamethasone

Pomalidomide DRUG

predetermined dose, orally, daily per cycle

Also known as: Pomalyst, Imnovid

Daratumumab,Carfilzomib, Pomalidomide and Dexamethasone

Dexamethasone DRUG

predetermined dose, orally, given 8 times per cycle

Also known as: Dexasone, Diodex, hexadrol

Daratumumab,Carfilzomib, Pomalidomide and Dexamethasone

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women ≥ 18 and ≤ 80 years old
• Diagnosis of multiple myeloma:
• Serum monoclonal protein ≥ 0.5 g/dL. Patients with IgD disease and lower amounts of monoclonal protein may be permitted to enroll with PI approval
• ≥ 200 mg of monoclonal protein in the urine on 24 hour electrophoresis
• Serum free light chain ≥ 100 mg/L (10 mg/dL) and abnormal serum free kappa to serum free kappa light chain ratio
• Previously treated relapsed and refractory multiple myeloma
• Patients must have received at least one prior line of therapy;
• Prior therapy must include at least 2 cycles of lenalidomide and at least 2 cycles of a proteasome inhibitor (either in separate regimens or within the same regimen)
• Disease progression on or within 60 days of completion of last therapy.
• ANC ≥ 1000/μL.
• G-CSF is not permitted within 14 days of screening.
• Patients with ANC \<1000/µL can be considered for screening on a case by case basis with additional monitoring, after discussion with and approval from the PI.
• Platelet count ≥ 50,000/µL. Platelet transfusion is not permitted within 7 days of screening.
• Hemoglobin ≥ 8 g/dL. Red blood cell transfusions are permitted to meet eligibility criteria.
• Calculated creatinine clearance of ≥ 30 mL/min by Cockcroft-Gault equation.

You may not qualify if:

• Participants who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to study registration or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier. Patients may have received dexamethasone within 2 weeks prior to study registration.
• Participants who are receiving any other investigational agents.
• Last line of therapy with the combination of carfilzomib, pomalidomide, and dexamethasone. Note, prior treatment with daratumumab or other anti-CD38 therapy is permitted. Prior treatment with carfilzomib or pomalidomide is permitted (as different lines of treatment but not in the same combination).
• Concomitant high dose corticosteroids. Low dose corticosteroids (maximum dose 10 mg/day prednisone equivalent) is permitted if given for disorders other than myeloma, e.g. adrenal insufficiency, rheumatoid arthritis, etc.
• Pregnancy or lactation or planned lactation (breastfeeding).
• Prior history of malignancies, other than MM, unless the patient has completed definitive treatment and has been free of the disease for ≥ 3 years. Patients who are free of disease \< 3 years may enroll after discussion with and approval of the PI. Exceptions include the following (i.e. the following are eligible to participate):
• Basal or squamous cell carcinoma of the skin
• Carcinoma in situ of the cervix
• Ductal carcinoma in situ of the breast
• Incidental histologic finding of prostate cancer (T1a or T1b) managed with surveillance
• Patients with plasma cell leukemia, POEMS syndrome, or amyloidosis are excluded from this trial.
• Seropositive for HIV infection
• Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]; see exception below). Subjects with resolved infection (ie, 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 prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
• Seropositive for hepatitis C (except in the setting of a sustained virologic response \[SVR\], defined as aviremia at least 12 weeks after completion of antiviral therapy).
• Peripheral neuropathy ≥ grade 2 despite supportive therapy.

Sponsors & Collaborators

• Andrew Yee, MD: lead
• Amgen: collaborator
• Janssen Research & Development, LLC: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02155, United States

RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

daratumumab; carfilzomib; pomalidomide; 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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Andrew J Yee, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrew J Yee, MD

CONTACT

617-726-2000; ayee1@mgh.harvard.edu

Study Design

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

Study Record Dates

• First Submitted: November 22, 2019
• First Posted: November 25, 2019
• Study Start: May 18, 2020
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2028
• Last Updated: October 7, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: \- MGH - Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (3)