Fenofibrate to prevent nerve damage from VRd (bortezomib/lenalidomide/dexamethasone) in multiple myeloma

Clinical Study to Evaluate the Possible Role of Fenofibrate in the Prophylaxis From Peripheral Neuropathy Induced by Bortezomib, Lenalidomide and Dexamethasone Protocol in the Treatment of Patients With Multiple Myeloma

This tests whether adding fenofibrate to standard VRd chemotherapy can reduce bortezomib-related peripheral neuropathy in adults newly diagnosed with multiple myeloma.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 44 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Tanta University (other)
• Drugs / interventions: chemotherapy
• Locations: 2 sites (Damanhur, El- Behira and 1 other locations)
• Trial ID: NCT07025005 on ClinicalTrials.gov

What this trial studies

This interventional phase 4 study compares standard VRd induction chemotherapy alone to VRd plus fenofibrate 160 mg in adults with newly diagnosed multiple myeloma. Participants receive six 28-day cycles of bortezomib, lenalidomide, and dexamethasone, with the fenofibrate group taking daily 160 mg tablets. Neuropathy is monitored every two cycles using NCI-CTCAE v5 and the FACT/GOG-Ntx-12 questionnaire, and blood biomarkers BDNF and neurofilament light chain (NfL) are measured. Outcomes will compare neuropathy scores and biomarker changes between groups to see if fenofibrate reduces the frequency or severity of bortezomib-induced peripheral neuropathy.

Who should consider this trial

Good fit: Adults (≥18) with newly diagnosed multiple myeloma starting VRd induction, ECOG performance status <2, adequate blood, liver, and renal function, and no recent exposure to other neurotoxic agents are ideal candidates.

Not a fit: Patients with preexisting moderate-to-severe neuropathy, recent exposure to other neurotoxic agents, concurrent use of excluded neuropathic medications, or contraindications to fenofibrate may not receive benefit.

Why it matters

Potential benefit: If successful, fenofibrate could lower the incidence or severity of bortezomib-induced peripheral neuropathy, preserving patients' quality of life and allowing uninterrupted myeloma therapy.

How similar studies have performed: Preclinical studies showed fenofibrate reduced chemotherapy-induced neuropathy in animal models (e.g., paclitaxel), but clinical evidence specifically for bortezomib-induced neuropathy is novel and limited.

Eligibility criteria

Inclusion Criteria:

* Age ≥ 18 years old.
* Newly diagnosed MM patients according to the revised International Myeloma Working Group Diagnostic Criteria for the diagnosis of Multiple Myeloma (IMWG).
* Patients being treated by bortezomib-based VRd chemotherapy regimen.
* Patients with performance status \<2 according to Eastern Cooperative Oncology Group (ECOG) score.
* Adequate baseline hematologic values (absolute neutrophilic count ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L and hemoglobin level ≥ 10 g/dl).
* Patients with adequate liver function (serum bilirubin \< 1.2 mg/dl) and adequate renal function (serum creatinine \< 1.5 mg/d).

Exclusion Criteria:

* Patients with prior exposure to neurotoxic agents (Cis-platin, vincristine, taxanes, foscarnet, INH, etc..) in the last 6 months.
* Concomitant use of antioxidant vitamins (vitamin A, C, E), anticonvulsants, tricyclic antidepressants, other medications used for neuropathic pain (gabapentin, lamotrigine, carbamazepine).
* Preexisting peripheral neuropathy resulting from other causes such as diabetes and brain disorders, hypothyroidism, autoimmune diseases, hepatitis C.
* Patients with inflammatory diseases (ulcerative colitis, rheumatoid arthritis).
* Patients with conditions associated with oxidative stress (smoking, tuberculosis, comorbid obesity).
* Patients with active liver disease (cirrhosis, fatty liver, hepatitis C, etc..).
* Patients with myopathy.
* Patients with other malignancies.
* Patients with renal impairment, including those with end-stage renal disease and those receiving dialysis.
* Patients with Gallbladder disease and gallstones.
* Pregnant and breast-feeding women.
* Patients with Known allergy to the fenofibrates.
* Concurrent use of statin, colchicine, Ciprofibrate, idelalisib, enzyme inducers (phenytoin, phenobarbitone, carbamazepine,…), enzyme inhibitors (ketoconazole, clarithromycin,…), drugs with high plasma protein binding capacity (Sulfonamides, valproate, oral hypoglycemic, warfarin,…) to avoid potential pharmacodynamics and pharmacokinetic drug interactions.

Where this trial is running

Damanhur, El- Behira and 1 other locations

• Damanhur Oncology Center — Damanhur, El- Behira, Egypt (RECRUITING)
• Tanta University — Tanta, El-Gharbya, Egypt (RECRUITING)

Study contacts

• Principal investigator: Ashraf M Alaa, BSc of clinical pharmacy — clinical pharmacy departement - Faculty of Pharmacy - Tanta University
• Study coordinator: Ashraf M Alaa, BSc of clinical pharmacy

Conditions: Peripheral Neuropathy, Multiple Myeloma, Neoplasms, peripheral neuropathy, multiple myeloma, bortezomib induced peripheral neuropathy, Fenofibrate, VRd protocol, lenalidomide