Actively Recruiting
ATRA and Carfilzomib in Plasma Cell Myeloma Patients
Led by The Methodist Hospital Research Institute · Updated on 2026-04-03
42
Participants Needed
1
Research Sites
309 weeks
Total Duration
On this page
Sponsors
T
The Methodist Hospital Research Institute
Lead Sponsor
C
Cancer Prevention Research Institute of Texas
Collaborating Sponsor
AI-Summary
What this Trial Is About
This is a Phase IB/II trial that will investigate the safety, tolerability and efficacy of combination therapy using All-Trans Retinoic Acid (ATRA) with Carfilzomib based therapies in plasma cell myeloma also commonly referred as Multiple Myeloma (MM), in patients considered refractory to proteasome inhibitors (PIs). Multiple myeloma is an incurable clonal plasma cell disorder that comprises 10% of all hematologic malignancies. Over the past 30 years the global prevalence of multiple myeloma has risen to 126%, with 85% of diagnoses occurring in patients \>55 years of age. In the past 15 years, survival has improved considerably, which is attributed to the development of multiple different classes of medications, including proteasome inhibitors. Proteasome inhibitors are the foundation of many multiple myeloma treatments in both transplant eligible and ineligible patients for the past 2 decades. While proteasome inhibitors have improved both progression free survival (PFS) and overall survival (OS), many patients eventually develop disease progression arising from resistance to therapies. As a result, there is an unmet need to overcome resistance and find ways to enhance multiple myeloma sensitivity to proteasome inhibitor toxicity. Carfilzomib, a modified peptide epoxyketone that selectively targets intracellular proteasome enzymes, is approved in combination with dexamethasone in patients that have received ≥1 line of therapy or in combination. There are few studies assessing ways to enhance carfilzomib-mediated multiple myeloma toxicity. All-Trans Retinoic Acid (ATRA) is an oxidative metabolite of retinol (vitamin A) and plays an important role in the regulation of cellular proliferation and differentiation. In a recent pre-clinical study, ATRA was found to enhance sensitivity of carfilzomib-mediated apoptosis in vitro via an interferon beta (IFN-β) response pathway. In the clinical setting, ATRA is a well-tolerated drug that has shown little change in the rate of adverse events in early clinical trials with multiple myeloma. The investigators hypothesize that ATRA enhances sensitivity of multiple myeloma to carfilzomib therapy.
CONDITIONS
Official Title
ATRA and Carfilzomib in Plasma Cell Myeloma Patients
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age 18 years or older with relapsed/refractory multiple myeloma confirmed by international criteria
- Previously treated with at least three therapy lines including immunomodulatory drugs, proteasome inhibitors (including carfilzomib), and anti-CD38 antibodies
- Failed to achieve minor response after at least two cycles of carfilzomib-based therapy or relapsed during therapy
- Able and willing to sign informed consent
- Eastern Cooperative Oncology Group performance status of 2 or less
- Adequate organ function including hemoglobin ≥8 g/dL, platelets >75,000, neutrophils >1000/µL, left ventricular ejection fraction ≥50%, creatinine clearance ≥30 ml/min, liver enzymes ≤3 times upper limit of normal, and total bilirubin ≤1.5 times upper limit of normal
- Measurable disease requiring treatment by serum or urine M protein or serum free light chain levels
- Fully recovered from any prior autologous stem cell transplant and at least 60 days post-transplant with hematologic recovery
- Willing to undergo bone marrow biopsy if required
- Life expectancy of at least 6 months
- Use of effective birth control methods for women of childbearing potential and men as specified with negative pregnancy test before treatment start
You will not qualify if you...
- Non-secretory or hyposecretory multiple myeloma with low M-protein or only measurable by serum free light chain
- Plasma cell leukemia (except if previously treated and approved by investigator)
- Concurrent light chain amyloidosis
- Central nervous system involvement such as brain metastases
- Pregnant or breastfeeding women
- Severe or active infections or neutropenia with fever within one week prior to treatment
- History of allogeneic stem cell or solid organ transplant
- Unstable angina, significant cardiac arrhythmia, or heart failure greater than NYHA class II
- Significant recent medical or social conditions that would prevent study participation
- Received investigational therapies within 12 weeks before enrollment
- History of allergic reaction or intolerance to proteasome inhibitors including carfilzomib, bortezomib, or ixazomib
- Deemed unfit for study participation by the investigator
AI-Screening
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Trial Site Locations
Total: 1 location
1
Houston Methodist Neal Cancer Center
Houston, Texas, United States, 77030
Actively Recruiting
Research Team
S
Sai Ravi Pingali, MD
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
1
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