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OncoMatch/Clinical Trials/NCT06536413

ATRA and Carfilzomib in Plasma Cell Myeloma Patients

Is NCT06536413 recruiting? Yes, currently enrolling (May 2026). This Phase 1/2 trial studies multiple treatments including All-Trans Retinoic Acid (ATRA) Dose 0 and All-Trans Retinoic Acid (ATRA) Dose -1 for multiple myeloma.

Phase 1/2RecruitingThe Methodist Hospital Research InstituteNCT06536413Data as of May 2026

Treatment: All-Trans Retinoic Acid (ATRA) Dose 0 · All-Trans Retinoic Acid (ATRA) Dose -1 · All-Trans Retinoic Acid (ATRA) Dose 1This 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.

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Extracted eligibility criteria

Cancer type

Multiple Myeloma

Performance status

ECOG 0–2(Ambulatory, capable of self-care)

Prior therapy

Min 3 prior lines

Must have received: immunomodulatory drug

Previously treated with at least three lines of therapy which would include Immunomodulatory drugs (IMiDs)

Must have received: proteasome inhibitor (carfilzomib)

Proteosome inhibitors (including carfilzomib)

Must have received: anti-CD38 antibody

anti-CD 38 antibodies

Must have received: carfilzomib-based therapy (carfilzomib)

failed to achieve a minor response after completing at least 2 cycles of carfilzomib-based therapy or are relapsed while on therapy

Cannot have received: allogeneic hematopoietic cell transplantation

History of Allogeneic hematopoietic cell transplantation

Cannot have received: solid organ transplantation

History of ... solid organ transplantation

Cannot have received: proteasome inhibitor (carfilzomib, bortezomib, ixazomib)

Exception: previous allergic reaction or intolerance

Previous allergic reaction or intolerance to a proteasome inhibitor, including carfilzomib, bortezomib, or ixazomib

Cannot have received: investigational therapy

On investigational therapies within 12 weeks of enrollment

Lab requirements

Blood counts

Hemoglobin ≥8 g/dL (baseline or after Peripheral Red Blood Cell transfusion), Platelet count >75,000 and Absolute Neutrophil Count >1000/ micro liter

Kidney function

Creatinine Clearance ≥ 30 ml/min

Liver function

AST and ALT ≤ 3 × ULN; Total bilirubin ≤ 1.5 × ULN

Cardiac function

Left Ventricular Ejection fraction ≥50%

Adequate organ function defined as: Hemoglobin ≥8 g/dL (baseline or after Peripheral Red Blood Cell transfusion), Platelet count >75,000 and Absolute Neutrophil Count >1000/ micro liter. Left Ventricular Ejection fraction ≥50%. Creatinine Clearance ≥ 30 ml/min. AST and ALT ≤ 3 × ULN. Total bilirubin ≤ 1.5 × ULN.

Structured fields extracted by AI. May contain errors — verify against the official protocol.

US trial sites

  • Houston Methodist Neal Cancer Center · Houston, Texas

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