Quad Therapy for Multiple Myeloma
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Andrew Yee, MD
Must be taking: Acetylsalicylic acid
Must not be taking: Investigational agents
Disqualifiers: Pregnancy, HIV, Hepatitis B, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?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
Do I need to stop my current medications to join the trial?
The trial protocol does not specify if you need to stop your current medications. However, you cannot be on high-dose corticosteroids or any other investigational agents. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the drug combination used in the Quad Therapy for Multiple Myeloma?
Research shows that pomalidomide combined with low-dose dexamethasone is effective for patients with relapsed and refractory multiple myeloma, improving survival rates and response to treatment. Carfilzomib, another component of the therapy, has also shown significant activity in similar patient groups, indicating that these drugs can be effective in treating multiple myeloma.
12345Is Quad Therapy for Multiple Myeloma safe for humans?
Research shows that Quad Therapy, which includes drugs like carfilzomib, pomalidomide, dexamethasone, and sometimes daratumumab, is generally well-tolerated in patients with relapsed or refractory multiple myeloma. Common side effects include low blood cell counts, fatigue, and infections, but serious side effects are rare. Overall, the treatment is considered safe for use in humans with this condition.
15678What makes the Quad Therapy for Multiple Myeloma unique?
The Quad Therapy for Multiple Myeloma is unique because it combines four different types of drugs: carfilzomib (a proteasome inhibitor), daratumumab (a monoclonal antibody), dexamethasone (a steroid), and pomalidomide (an immunomodulatory drug). This combination aims to enhance treatment effectiveness by targeting the cancer cells in multiple ways, potentially offering a more comprehensive approach compared to traditional treatments that use fewer drugs.
69101112Eligibility Criteria
This trial is for adults aged 18-80 with relapsed or treatment-resistant multiple myeloma, who have undergone specific prior therapies and show disease progression. Participants must be able to take oral medication, have adequate organ function, agree to use birth control if applicable, and not have a history of significant illness or recent major treatments that could interfere with the study.Inclusion Criteria
Agreement to use birth control if sexually active and not sterile
My multiple myeloma has returned or didn't respond to treatment and has gotten worse.
I can swallow pills without any issues.
+4 more
Exclusion Criteria
I do not have severe nerve damage, severe allergies, or a recent stem cell transplant.
I have used specific treatments and steroids for my condition.
I do not have any health or social issues that would affect my participation in the study.
+9 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive daratumumab, carfilzomib, pomalidomide, and dexamethasone on a 28-day schedule
28 days per cycle
Weekly visits for drug administration
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Long-term follow-up
Progression-free survival and minimal residual disease status are monitored
Up to 60 months
Participant Groups
The study is testing a combination of two investigational drugs (Carfilzomib and Daratumumab) with two standard care medications (Dexamethasone and Pomalidomide) in patients with multiple myeloma that has returned after treatment or hasn't responded to previous therapy.
1Treatment groups
Experimental Treatment
Group I: Daratumumab,Carfilzomib, Pomalidomide and DexamethasoneExperimental Treatment4 Interventions
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.
Carfilzomib is already approved in United States, European Union, Canada, Japan for the following indications:
🇺🇸 Approved in United States as Kyprolis for:
- Multiple myeloma
🇪🇺 Approved in European Union as Kyprolis for:
- Multiple myeloma
🇨🇦 Approved in Canada as Kyprolis for:
- Multiple myeloma
🇯🇵 Approved in Japan as Kyprolis for:
- Multiple myeloma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Massachusetts General HospitalBoston, MA
Dana-Farber Cancer InstituteBoston, MA
Beth Israel Deaconess Medical CenterBoston, MA
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Who Is Running the Clinical Trial?
Andrew Yee, MDLead Sponsor
AmgenIndustry Sponsor
Janssen Research & Development, LLCIndustry Sponsor
References
Safety and efficacy of pomalidomide plus low-dose dexamethasone in STRATUS (MM-010): a phase 3b study in refractory multiple myeloma. [2021]Patients with relapsed and/or refractory multiple myeloma (RRMM) have poor prognosis. The STRATUS study assessed safety and efficacy of pomalidomide plus low-dose dexamethasone in the largest cohort to date of patients with RRMM. Patients who failed treatment with bortezomib and lenalidomide and had adequate prior alkylator therapy were eligible. Pomalidomide 4 mg was given on days 1-21 of 28-day cycles with low-dose dexamethasone 40 mg (20 mg for patients aged >75 years) on days 1, 8, 15, and 22 until progressive disease or unacceptable toxicity. Safety was the primary end point; secondary end points included overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Among 682 patients enrolled, median age was 66 years, and median time since diagnosis was 5.3 years. Median number of prior regimens was 5. Most patients were refractory to both lenalidomide and bortezomib (80.2%). Median follow-up was 16.8 months; median duration of treatment was 4.9 months. Most frequent grade 3/4 treatment-emergent adverse events were hematologic (neutropenia [49.7%], anemia [33.0%], and thrombocytopenia [24.1%]). Most common grade 3/4 nonhematologic toxicities were pneumonia (10.9%) and fatigue (5.9%). Grade 3/4 venous thromboembolism and peripheral neuropathy were rare (1.6% each). The ORR was 32.6%, and the median DOR was 7.4 months. Median PFS and OS were 4.6 months and 11.9 months, respectively. We present the largest trial to date evaluating pomalidomide plus low-dose dexamethasone in patients with RRMM, further confirming that this regimen offers clinically meaningful benefit and is generally well tolerated. www.Clinicaltrials.gov identifier NCT01712789.
Pomalidomide: A Review in Relapsed and Refractory Multiple Myeloma. [2018]Pomalidomide (Imnovid®; Pomalyst®), an analogue of thalidomide, is an immunomodulatory agent, with several mechanisms of action (both direct and indirect) thought to be involved in its anti-myeloma activity. Oral pomalidomide is available in several countries for use in combination with low-dose dexamethasone in adults with relapsed and refractory multiple myeloma. In multinational, phase II or III studies in patients with refractory, or relapsed and refractory multiple myeloma who had received ≥ 2 prior treatment regimens (including ≥ 2 cycles of both lenalidomide and bortezomib), pomalidomide plus low-dose dexamethasone was associated with prolonged progression-free survival (PFS) and overall survival and an improved overall response rate. Pomalidomide plus low-dose dexamethasone had a manageable tolerability profile, with neutropenia, infections, anaemia and thrombocytopenia being the most frequently reported grade 3 or 4 treatment-emergent adverse events. In conclusion, pomalidomide plus low-dose dexamethasone extends the treatment options available for the management of relapsed and refractory multiple myeloma in a patient population that has very limited treatment options.
Pomalidomide: a review of its use in patients with recurrent multiple myeloma. [2022]Oral pomalidomide (Imnovid® [EU]; Pomalyst® [USA]) in combination with dexamethasone (in the EU), is approved in several countries for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least two prior therapies, including lenalidomide and bortezomib, and have demonstrated disease progression on the last therapy (or progression within the last 60 days in the USA). The key therapeutic mechanisms of action of pomalidomide, a thalidomide analogue, reside in its immunomodulatory, antiproliferative and anti-angiogenic effects. In the pivotal, multinational phase II MM-002 and phase III MM-003 trials, pomalidomide plus low-dose dexamethasone was effective and had a manageable safety and tolerability profile in adult patients with relapsed and refractory multiple myeloma who had received at least two prior antimyeloma therapies, including at least 2 cycles of both lenalidomide and bortezomib. Moreover, compared with high-dose dexamethasone, treatment with pomalidomide plus low-dose dexamethasone significantly prolonged progression-free survival, overall survival and time to disease progression, and improved overall response rates in the intent-to-treat population. In general, improvements in these clinical outcomes with pomalidomide plus low-dose dexamethasone treatment were also observed in subgroups of patients, including those refractory to lenalidomide, bortezomib or both drugs, those who had received several prior antimyeloma therapies, patients with renal impairment, elderly patients and those with a high-risk cytogenetic profile. Thus, combination therapy with pomalidomide plus low-dose dexamethasone is an important emerging treatment option for use as salvage therapy in patients with relapsed and refractory multiple myeloma.
New drugs in multiple myeloma - role of carfilzomib and pomalidomide. [2021]Carfilzomib (CFZ), an epoxyketone with specific chymotrypsin-like activity, is a second-generation proteasome inhibitor with significant activity in patients with relapsed and refractory multiple myeloma. On July 20, 2012, the US Food and Drug Administration approved CFZ to treat patients with multiple myeloma who have received at least two prior therapies including bortezomib (BORT) and an immunomodulatory agent and have demonstrated disease progression on or within 60 days of completion of the last therapy. Cytogenetic abnormalities did not appear to have a significant impact on the CFZ activity. Carfilzomib was well tolerated and demonstrated promising efficacy in patients with renal insufficiency. Pomalidomide (POM) (CC-4047) is a novel immunomodulatory derivative (IMID) with a stronger in vitro anti-myeloma effect compared with "older" IMIDs - thalidomide and lenalidomide (LEN). On February 8, 2013, the US Food and Drug Administration approved POM (Pomalyst, Celgene) for the treatment of MM patients who have received at least two prior therapies including LEN and BORT and have demonstrated progression on or within 60 days of completion of the last therapy. Pomalidomide is a novel IMID with significant anti-myeloma activity and manageable toxicity. This compound has shown high efficacy in MM patients who were resistant to prior use of LEN/BORT as well as in patients with a high-risk cytogenetic profile. Carfilzomib and POM have very high efficacy and will be used also in first line therapy in future.
Treatment-related adverse events in patients with relapsed/refractory multiple myeloma. [2017]In the past decade we have seen four new agents approved by the US Food and Drug Administration for treatment of multiple myeloma: the proteasome inhibitor (PI) bortezomib (Velcade), the immunomodulatory agents lenalidomide (Revlimid) and thalidomide (Thalomid), and liposomal doxorubicin. These are commonly used in the treatment of relapsed/refractory (R/R) multiple myeloma (MM), but there is no universally accepted standard treatment. Salvage therapy must be tailored according to an individual patient's clinical profile, with the risks and potential effects of treatment-related adverse events being major determinants of the choice of therapy. Two novel agents in phase II studies to investigate their potential for the treatment of R/R MM are carfilzomib, a selective, irreversible next-generation PI, and pomalidomide, a next-generation thalidomide analog. This review will discuss the side-effect profiles of the currently approved immunomodulatory agents and bortezomib, as well as those of the newer agents, carfilzomib and pomalidomide.
Phase I study of carfilzomib, lenalidomide, vorinostat, and dexamethasone in patients with relapsed and/or refractory multiple myeloma. [2022]Research has shown that proteasome inhibitors (e.g., carfilzomib), immunomodulatory agents (e.g., lenalidomide), histone deacetylase inhibitors (e.g., vorinostat) and corticosteroids (e.g., dexamethasone) have synergistic anti-multiple myeloma (MM) activity. This phase I dose-escalation study evaluated a regimen combining carfilzomib, lenalidomide, vorinostat and dexamethasone (QUAD) in patients with relapsed and/or refractory MM. Seventeen patients received carfilzomib (15, 20, or 20/27 mg/m(2) ; 30-min infusion; days 1, 2, 8, 9, 15, 16), lenalidomide (15 or 25 mg; days 1-21), vorinostat (300 or 400 mg; days 1-7, 15-21), and dexamethasone (40 mg; days 1, 8, 15, 22) in 28-d cycles. No dose-limiting toxicities were observed; the maximum tolerated dose was not reached. The maximum administered dose was carfilzomib 20/27 mg/m(2) , lenalidomide 25 mg, vorinostat 400 mg, and dexamethasone 40 mg. Common grade ≥3 adverse events included neutropenia (53%), thrombocytopenia (53%) and anaemia (41%). The overall response rate was 53%: 12% of patients achieved a very good partial response (PR) and 41% of patients achieved a PR. At a median follow-up of 10 months, median progression-free survival was 12 months and median overall survival was not reached. Treatment with QUAD was feasible and had encouraging activity in patients with relapsed and/or refractory MM.
Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma. [2022]Treatment options for patients with heavily pretreated relapsed and/or refractory multiple myeloma remain limited. We evaluated a novel therapeutic regimen consisting of carfilzomib, pomalidomide, and dexamethasone (CPD) in an open-label, multicenter, phase 1, dose-escalation study. Patients who relapsed after prior therapy or were refractory to the most recently received therapy were eligible. All patients were refractory to prior lenalidomide. Patients received carfilzomib IV on days 1, 2, 8, 9, 15, and 16 (starting dose of 20/27 mg/m(2)), pomalidomide once daily on days 1 to 21 (4 mg as the initial dose level), and dexamethasone (40 mg oral or IV) on days 1, 8, 15, and 22 of 28-day cycles. The primary objective was to evaluate the safety and determine the maximum tolerated dose (MTD) of the regimen. A total of 32 patients were enrolled. The MTD of the regimen was dose level 1 (carfilzomib 20/27 mg/m(2), pomalidomide 4 mg, dexamethasone 40 mg). Hematologic adverse events (AEs) occurred in ≥60% of all patients, including 11 patients with grade ≥3 anemia. Dyspnea was limited to grade 1/2 in 10 patients. Peripheral neuropathy was uncommon and limited to grade 1/2. Eight patients had dose reductions during therapy, and 7 patients discontinued treatment due to AEs. Two deaths were noted on study due to pneumonia and pulmonary embolism (n = 1 each). The combination of CPD is well-tolerated and highly active in patients with relapsed/refractory multiple myeloma. This trial was registered at www.clinicaltrials.gov as #NCT01464034.
Phase 1/2 study of carfilzomib, pomalidomide, and dexamethasone with and without daratumumab in relapsed multiple myeloma. [2023]We conducted a phase 1/2 study of carfilzomib, pomalidomide, and dexamethasone (KPd) and KPd with daratumumab (Dara-KPd) in relapsed/refractory multiple myeloma. The primary end points were identification of a maximum tolerated dose (MTD) of KPd for phase 1, and rates of overall response (ORR) and near complete response (nCR) after 4 cycles of KPd and Dara-KPd, respectively, for phase 2. The MTD for KPd was carfilzomib 20/27 mg/m2 on days 1, 2, 8, 9, 15, and 16 (cycles 1-8) and days 1, 2, 15, and 16 for cycles 9 and beyond; oral pomalidomide 4 mg on days 1 to 21; and oral dexamethasone 40 mg weekly in 28-day cycles. Sixty-six patients received KPd, including 34 at the MTD. The ORR after 4 cycles of KPd at the MTD was 27/34 (79%; 95% confidence interval [CI], 62%-91%), meeting the statistical threshold for efficacy. At a median follow-up of 44 months, the median progression-free survival (PFS) was 13 months and overall survival (OS) 44 months. Twenty-eight patients received Dara-KPd. The rate of nCR or better after 4 cycles was 11/28 (39%; 95% CI, 22%-59%), meeting the statistical threshold for efficacy. As the best response to Dara-KPd, the ORR was 25/28 (89%) and the rate of measurable residual disease negativity by flow cytometry (10-5) was 17/26 (65%). At a median follow-up of 26 months, the median PFS and OS for Dara-KPd were not reached. Dara-KPd induced deeper and more durable responses than KPd without compromising safety in a predominantly high-risk, lenalidomide-refractory population, warranting further evaluation of this quadruplet. This trial is registered at www.clinicaltrials.gov as #NCT01665794.
Elotuzumab and Weekly Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Without Transplant Intent: A Phase 2 Measurable Residual Disease-Adapted Study. [2023]Treatment of newly diagnosed multiple myeloma (NDMM) with a quadruplet regimen consisting of a monoclonal antibody, proteasome inhibitor, immunomodulatory imide, and corticosteroid has been associated with improved progression-free survival (PFS) compared with triplet regimens. The optimal quadruplet combination, and whether this obviates the need for frontline autologous stem cell transplant (ASCT), remains unknown. We evaluated elotuzumab and weekly carfilzomib, lenalidomide, and dexamethasone (Elo-KRd) without ASCT in NDMM.
Daratumumab Plus Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma. [2022]Combination therapy regimens containing a proteasome inhibitor, an immunomodulatory drug, and a steroid are an established standard of care for patients with newly diagnosed multiple myeloma (NDMM) regardless of transplant eligibility. Triplet regimens that include lenalidomide/dexamethasone combined with daratumumab or carfilzomib are highly active in multiple myeloma, including NDMM. The aim of this open-label, phase 1b study was to evaluate daratumumab in combination with carfilzomib, lenalidomide, and dexamethasone (D-KRd) in patients with NDMM.
How I treat myeloma with new agents. [2021]At present, multiple classes of agents with distinct mechanisms of action are available for the treatment of patients with multiple myeloma (MM), including alkylators, steroids, immunomodulatory agents (IMiDs), proteasome inhibitors (PIs), histone deacetylase inhibitors (DACIs), and monoclonal antibodies (mAbs). Over the last 5 years, several new agents, such as the third-generation IMiD pomalidomide, the second-generation PIs carfilzomib and ixazomib, the DACI panobinostat, and 2 mAbs, elotuzumab and daratumumab, have been approved, incorporated into clinical guidelines, and have transformed our approach to the treatment of patients. These agents may be part of doublet or triplet combinations, or incorporated into intensive strategies with autologous stem cell transplantation. In this review, I discuss the different treatment options available today for the treatment of MM in frontline and relapse settings.
Daratumumab: A Review in Combination Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma. [2021]Intravenous daratumumab (DARZALEX®), a human monoclonal antibody targeting CD38, is approved in the EU and USA for use in combination with bortezomib, thalidomide and dexamethasone for the treatment of adults with newly diagnosed multiple myeloma (MM) who are eligible for autologous stem cell transplantation. A subcutaneous formulation of daratumumab has also been approved in the EU and USA (DARZALEX FASPRO™) for use in MM. In the pivotal phase III CASSIOPEIA trial in adults with newly diagnosed, transplant-eligible MM, the addition of intravenous daratumumab to bortezomib, thalidomide and dexamethasone significantly increased the proportion of patients with a stringent complete response and significantly prolonged progression-free survival; overall survival data are not yet mature. Some facets of health-related quality of life were improved by the addition of daratumumab. The addition of daratumumab had a minimal effect on overall toxicity and the most common grade ≥ 3 adverse events with daratumumab combination therapy were haematological (e.g. neutropenia, lymphopenia). The approval of daratumumab as combination therapy in patients with newly diagnosed, transplant-eligible MM expands the range of MM treatment settings in which daratumumab is an option and the availability of the subcutaneous formulation will likely be of benefit to patients.