NCT03159702

Propylene Glycol-Free Melphalan HCl (EVOMELA®) in Combination With Fludarabine and Total Body Irradiation Based Reduced Intensity Conditioning for Haploidentical Transplantation

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 43 (actual)
• Sponsor: Medical College of Wisconsin · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is an open-label, single-arm, phase II study to determine the safety of propylene glycol-free melphalan HCl (EVOMELA®), in combination with fludarabine and total-body irradiation-based reduced-intensity conditioning for haploidentical transplantation. In addition, the study evaluates the one-year progression-free survival of patients undergoing this treatment.

Detailed description

OVERVIEW: Elderly and infirm patients with hematological malignancies often cannot undergo allogeneic hematopoietic cell transplantation (HCT) because of high-toxicity rates and nonrelapse mortality (NRM) associated with higher-intensity conditioning allografts. Reduced-intensity conditioning (RIC) transplantation has emerged as an attractive alternative for these populations. FLUDARABINE/MELPHALAN. In RIC, fludarabine is often used as the lymphocyte-depleting component to facilitate donor-cell engraftment. This drug can be given once daily because of its plasma half-life. M.D. Anderson pioneered the use of fludarabine melphalan (FLU/MEL) conditioning, which has since gained wide usage. (1) Melphalan is convenient, has broad antitumor activity in hematologic malignancies and has immunosuppressive effects. The Flu/Mel conditioning regimen can provide long-term disease control, especially in the subset of patients with chemo sensitive disease. (1) TOTAL-BODY IRRADIATION. In a recent study, total-body irradiation (200 cGy) was used with flu/mel for advanced lymphoma treated with HCT. With a median follow-up time close to two years, the survival of these mostly advanced, relapsed/refractory patients was very encouraging with overall survival of 54% and progression-free survival of 54% for the entire group. (2) Treatment-related mortality was low at day 100 (9.1%) and two years (19%) after transplantation, with stable engraftment achieved in the great majority of patients. PROPYLENE GLYCOL-FREE MELPHALAN HCL (EVOMELA®). In theory, intensifying the dose of melphalan in flu/mel conditioning could provide better disease control post HCT, allowing more time for curative graft-versus-leukemia effects to emerge. The use of the commercial formulation of melphalan (Alkeran®) proved somewhat problematic, however, because it must be reconstituted with propylene glycol, a substance that has been associated with toxic side effects. The substitution of Captisol® in propylene glycol-free melphalan HCl (EVOMELA®) for Injection (Spectrum Pharmaceuticals, Inc.) for the excipients found in Alkeran®, directly overcomes the formulation limitations noted with Alkeran®. STUDY RATIONALE. The preliminary data suggest that the substitution of Captisol® in EVOMELA® for the excipients found in Alkeran® directly overcomes the formulation limitations and provides a potentially safer melphalan formulation for administration at higher doses used in HCT conditioning regimens. Based on these observations, we now propose a phase II study of a RIC regimen consisting of EVOMELA® in combination with fludarabine and total-body irradiation for patients undergoing haplo-HCT. The study will investigate the safety and tolerability of this conditioning approach. While the FDA indication for EVOMELA® is for myeloablative conditioning prior to autologous HCT in patients with multiple myeloma, we anticipate our study will provide critical preliminary data to explore this formulation in allogeneic HCT conditioning.

Conditions

• Hematological Malignancy
• Multiple Myeloma

Interventions

Type	Name	Description
DRUG	Evomela	140 mg/m\^2/day IV on Day -6 for patients who are \< 60 years of age. 70 mg/m\^2/day IV on Day -6 For patients who are ≥60 years or have a HCT-CI score of \>3
DRUG	Fludarabine	40 mg/ m\^2/day intravenous on Days: -5 -4, -3, -2
RADIATION	Total Body Irradiation	200 cGy on Day: -1
OTHER	Haploidentical Hematopoietic Cell Transplantation	This is a procedure that uses healthy blood-forming cells from a half-matched donor, typically a family member, to replace a patient's unhealthy ones.

Timeline

• Start date: 2017-12-08
• Primary completion: 2024-11-12
• Completion: 2025-12-08
• First posted: 2017-05-19
• Last updated: 2026-01-27
• Results posted: 2026-01-27

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study