Multiple MyelomaPhase 2NCT04176718
Daratumumab, Carfilzomib, Pomalidomide, Dexamethasone In MM
A Phase 2 study testing Daratumumab, Carfilzomib and Pomalidomide in people with Multiple Myeloma and Refractory Multiple Myeloma, run by Andrew Yee, MD at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Multiple Myeloma, Refractory Multiple Myeloma, Multiple Myeloma in Relapse
- What is being tested?
- Daratumumab, Carfilzomib and Pomalidomide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 3 sitesUnited States
- Study dates
- 18 May 2020to May 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
- Patient has adequate hepatic function, as evidenced by each of the following:
- Serum bilirubin values < 2 mg/dL; and
- Serum aspartate transaminase (ALT) and/or aspartate transaminase (AST) values < 2.5 × the upper limit of normal (ULN) of the institutional laboratory reference range. Patients with elevated bilirubin due to Gilbert's syndrome may be permitted with PI approval (e.g. total bilirubin <3 mg/dL and normal direct bilirubin).
- Must be able to take acetylsalicylic acid (ASA) daily as prophylactic anticoagulation. Patients intolerant to ASA may use low molecular weight heparin, apixaban, rivaroxaban, or equivalent.
- All study participants must be registered into the mandatory Pomalyst REMS program and be willing and able to comply with the requirements of the Pomalyst REMS program.
- Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Pomalyst REMS program.
- A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control e.g. either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the study and for 3 months after receiving the last dose of study drug.
- Able to swallow capsules whole (pomalidomide capsules cannot be crushed, dissolved or broken).
Who cannot join
- 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):
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- 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.
- Hypersensitivity to daratumumab, thalidomide, lenalidomide, pomalidomide, carfilzomib, or dexamethasone (such as Stevens-Johnson syndrome). Rash to immunomodulatory drug that can be medically managed is allowable.
- Allogeneic stem cell transplant <12 months prior to initiation of study treatment and who have not discontinued immunosuppressive treatment for at least four weeks prior to initiation of study treatment and who are currently dependent on such treatment. Patients may also not have active graft v. host disease (GVHD).
- Patient has a history of significant cardiovascular, neurological, endocrine, gastrointestinal, respiratory, or inflammatory illness that could preclude study participation, pose an undue medical hazard, or interfere with the interpretation of the study results, including, but not limited to, patients with congestive heart failure (New York Heart Association [NYHA] Class 3 or 4); unstable angina; cardiac arrhythmia; recent (within the preceding 6 months) myocardial infarction or stroke; hypertension requiring > 2 medications for adequate control; diabetes mellitus with > 2 episodes of ketoacidosis in the preceding 12 months; or chronic obstructive pulmonary disease (COPD) requiring > 2 hospitalizations in the preceding 12 months.
- Known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume [FEV] in 1 second <60% of predicted normal), known moderate or severe persistent asthma within 2 years prior to study registration (intermittent asthma is allowed). Patient with known or suspected COPD or asthma must have an FEV1 test within 28 days prior to study registration.
- Major surgery within 2 weeks prior to C1D1.
- Patient has any other medical, psychiatric, or social condition that would preclude participation in the study, pose an undue medical hazard, interfere with the conduct of the study, or interfere with interpretation of the study results.
- Toxicity from previous anticancer therapy must resolve to baseline levels or to grade ≤1, except for alopecia and peripheral neuropathy.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Massachusetts General Hospital
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, 02155
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
About this study
Official title: A Phase II Study of Daratumumab With Weekly Carfilzomib, Pomalidomide, and Dexamethasone in Relapsed and Refractory Multiple Myeloma
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
Read the detailed description
This phase II, multicenter, open-label study is studying daratumumab in combination with weekly carfilzomib, pomalidomide, and dexamethasone in people with relapsed and refractory multiple myeloma who have received at least one prior therapy and who have had previous treatment with both lenalidomide and a proteasome inhibitor.
- The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. 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
- A total of 43 participants will be enrolled to this trial
- The U.S. Food and Drug Administration (FDA) has not approved Daratumumab, and Carfilzomib for use in treatment of Multiple Myeloma.
- Being tested
- Daratumumab, Carfilzomib, Pomalidomide, Dexamethasone
- Keywords
- Multiple Myeloma, Refractory Multiple Myeloma, Multiple Myeloma in Relapse, Relapse
- Medical subject headings
- Multiple Myeloma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DaratumumabDrug
Also called Darzalex
predetermined dose, intravenously, at predetermined times per cycle
CarfilzomibDrug
Also called Kyprolis
predetermined dose, intravenously, give 3 times per cycle
PomalidomideDrug
Also called Pomalyst, Imnovid
predetermined dose, orally, daily per cycle
DexamethasoneDrug
Also called Dexasone, Diodex, hexadrol
predetermined dose, orally, given 8 times per cycle
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Daratumumab; Drug: Carfilzomib; Drug: Pomalidomide; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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%
Measured: 28 Days
Number of dose limiting toxicity grade 4 or higher treatment related
Measured: 28 Days
Secondary outcomes (2)
Progression-free survival (PFS)
PFS will be estimated using the Kaplan-Meier method
Measured: time from randomization to the disease progression or death from any cause up 60 months
Rate of Minimal residual disease (MRD) negative status
Clonal evolution and clonal heterogeneity will be summarized using descriptive statistics
Measured: 112 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2019
- Study start18 May 2020
- Primary completionMay 2027 (estimated)
- Study completionMay 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Andrew Yee, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen, Janssen Research & Development, LLC
- Responsible party
- Sponsor-investigator, Andrew Yee, MD, Massachusetts General Hospital
- Investigators
- Andrew J Yee, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04176718
- Sponsor's protocol ID
- 19-379
- Status last verified
- Oct 2026
- First submitted
- 22 Nov 2019
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Daratumumab With Weekly Carfilzomib, Pomalidomide, and Dexamethasone in Relapsed and Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT04176718
- Acronym / sponsor ID
- 19-379
- Keywords
- Multiple Myeloma, Refractory Multiple Myeloma, Multiple Myeloma in Relapse, Relapse
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Andrew Yee, MDUniversity, hospital or other
- Collaborators
- Amgen, Janssen Research & Development, LLC
- Study start
- 18 May 2020 (actual)
- Primary completion
- May 2027 (estimated)
- Study completion
- May 2028 (estimated)
- First posted
- 25 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
This phase II, multicenter, open-label study is studying daratumumab in combination with weekly carfilzomib, pomalidomide, and dexamethasone in people with relapsed and refractory multiple myeloma who have received at least one prior therapy and who have had previous treatment with both lenalidomide and a proteasome inhibitor.
- The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. 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
- A total of 43 participants will be enrolled to this trial
- The U.S. Food and Drug Administration (FDA) has not approved Daratumumab, and Carfilzomib for use in treatment of Multiple Myeloma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Daratumumab,Carfilzomib, Pomalidomide and Dexamethasone | Experimental | Drug: Daratumumab, Drug: Carfilzomib, Drug: Pomalidomide, Drug: DexamethasonePatients 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Men or women ≥ 18 and ≤ 80 years old
- Diagnosis of multiple myeloma:
- Previously treated relapsed and refractory multiple myeloma
- ANC ≥ 1000/μL.
- Platelet count ≥ 50,000/µL. Platelet transfusion is not permitted within 7 days of screening.
Key exclusion criteria (22 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DaratumumabAlso: Darzalexpredetermined dose, intravenously, at predetermined times per cycle | Drug | Daratumumab,Carfilzomib, Pomalidomide and Dexamethasone |
| CarfilzomibAlso: Kyprolispredetermined dose, intravenously, give 3 times per cycle | Drug | Daratumumab,Carfilzomib, Pomalidomide and Dexamethasone |
| PomalidomideAlso: Pomalyst, Imnovidpredetermined dose, orally, daily per cycle | Drug | Daratumumab,Carfilzomib, Pomalidomide and Dexamethasone |
| DexamethasoneAlso: Dexasone, Diodex, hexadrolpredetermined dose, orally, given 8 times per cycle | Drug | Daratumumab,Carfilzomib, Pomalidomide and Dexamethasone |
Primary outcome
Objective response rate of the daratumumab, carfilzomib, pomalidomide, and dexamethasone combination
Time frame: 28 Days
Simon's two-stage design will be used. An objective response rate of 40%
Number of dose limiting toxicity grade 4 or higher treatment related
Time frame: 28 Days
2 secondary outcomes
Progression-free survival (PFS)
Time frame: time from randomization to the disease progression or death from any cause up 60 months
Rate of Minimal residual disease (MRD) negative status
Time frame: 112 Days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2026.
- Individual participant dataSharing planned: Yes. The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew J Yee, MD principal investigator
Massachusetts General Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Daratumumab, Carfilzomib and Pomalidomide in people with Multiple Myeloma and Refractory Multiple Myeloma, run by Andrew Yee, MD at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate of the daratumumab, carfilzomib, pomalidomide, and dexamethasone combination (time frame: 28 Days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2026.