Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Hematologic Neoplasms

Hematologic Diseases

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Antineoplastic Agents

All Drugs and Chemicals

Fludarabine

Fludarabine phosphate

Melphalan

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

For patients who are \< 60 years.

* Melphalan: 140 mg/m2/day IV on Day: -6
* Fludarabine: 40 mg/ m2/day IV Days: -5 -4, -3, -2 (Adults: creatinine clearance (CrCl) may be estimated by the Cockcroft Formula: CrCl = \[(140-age) x weight (kg) x 0.85 (for women only)\]/ \[72 x creat (mg/dl)\].)
* TBI: 200 cGy Day: -1.

For patients who are ≥60 years and/or Hematopoietic Cell Transplant-Co-morbidity Index (HCT-CI) score of \>3 (at the discretion of treating physician will have an option to receive):

* Melphalan: 70 mg/m2/day IV on Day -6.
* Fludarabine: 40 mg/m2/day IV Days -5, -4, -3, -2.
* TBI: 200 cGy; Days -1.

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

Evomela

40 mg/ m\^2/day intravenous on Days: -5 -4, -3, -2

Total Body Irradiation

Medical College of Wisconsin Cancer Center Clinical Trials Office

Mehdi Hamadani, MD

Mehdi H Hamadani, MD

Mehdi Hamadani

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.

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.

Study subjects will receive different doses of Melphalan during the trial. This is done for safety per FDA recommendations. Subjects younger than 60 years or have will receive doses at 140 mg/m\^2/day while subject 60 years or old or have a Hematopoietic Cell Transplant-Co-morbidity Index (HCT-CI) score of \>3 will receive 70 mg/m\^2/day. The populations will be combined for analysis and reporting.

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

Progression-free survival (PFS) is defined as the length of time during and after the treatment that a participant lives with the disease but it does not get worse.

This is the number of participants expiring unrelated to relapse of disease.

The number of participants still alive at one year and 2 years.

The number of participants who relapse following reduced-intensity conditioning haploidentical transplantation at Day 100 and 1 Year.

The average of the number of days that it takes for neutrophil recovery from reduced-intensity conditioning haploidentical transplantation. Neutrophil recovery means absolute neutrophil count of 0.5x10\^3 cells/uL.

The average of the number of days that it takes for platelet recovery from reduced-intensity conditioning haploidentical transplantation. Platelet recovery means absolute neutrophil count of 50x10\^3 cells/uL.

The number of participants with graft-versus-host disease using the Center for International Bone Marrow Transplant Research criteria.

The number of participants with chronic GVHD at one-year post transplantation using the Center for International Bone Marrow Transplant Research criteria.

Number of subjects whose grafts failed to implant.

Spots Global Cancer Trial Database for evomela

Every month we try and update this database with for evomela cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for evomela

Every month we try and update this database with for evomela cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for evomela cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.