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

NCT03159702 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: PRO29507
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Multiple Myeloma; Hematological Malignancy

Keywords

hematological malignancy; EVOMELA; Melphalan HCl; Total Body Irradiation; Reduced Intensity Conditioning; Haploidentical Transplantation; Fludarabine; Hematologic Diseases

Outcome Measures

Primary Outcomes (2)

• Progression-free Survival (PFS) of Participants With Hematological Malignancies Undergoing Treatment.

  Progression-free survival (PFS) is defined as the interval from the date of transplantation to the earlier of the following events: (1) the first documented objective disease progression; (2) death from any cause. Subjects without documented PD/death will be censored at the earliest of the of the following times: (1) the starting time of a new treatment other than the study treatment; (2) the last efficacy assessment date.

  1 year

• Serious Adverse Events (SAE).

  An SAE is defined as any untoward medical occurrence at any dose, including death, life threatening, hospitalization, disability/incapacity, medically important event. The measure of this outcome is the number of participants with SAEs.

  2 Years

Secondary Outcomes (8)

• Nonrelapse Mortality Rate.

  1 Year

• Overall Survival

  1 Year and 2 Year

• Number of Subjects With Relapse of Disease.

  Day 100 and 1 Year

• Neutrophil Recovery

  Day 30

• Platelet Recovery

  Day 30

Study Arms (1)

MEL/FLU and Total-Body Irradiation (TBI)

EXPERIMENTAL

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.

Drug: Evomela; Drug: Fludarabine; Radiation: Total Body Irradiation; Other: Haploidentical Hematopoietic Cell Transplantation

Interventions

Evomela DRUG

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

Also known as: Melphalan

MEL/FLU and Total-Body Irradiation (TBI)

Fludarabine DRUG

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

Also known as: Fludara

MEL/FLU and Total-Body Irradiation (TBI)

Total Body Irradiation RADIATION

200 cGy on Day: -1

MEL/FLU and Total-Body Irradiation (TBI)

Haploidentical Hematopoietic Cell Transplantation OTHER

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.

MEL/FLU and Total-Body Irradiation (TBI)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with a diagnosis of hematological malignancy undergoing a related donor haploidentical HCT.\*
• Patients aged ≥18 are eligible.
• Bilirubin ≤ 2 x the upper limit of normal (ULN). For patients with Gilbert's syndrome or suspected mild veno-occlusive disease, bilirubin ≤ 3 x ULN is permitted.
• Adequate renal function as defined by a serum creatinine clearance of \> 30 mL/min calculated by Cockcroft-Gault equation.
• Left ventricular ejection fraction ≥40%. No uncontrolled arrhythmias or New York Heart Association class III-IV heart failure.
• Forced expiratory volume (FEV1) or diffusion capacity for carbon monoxide (DLCO) corrected for hemoglobin ≥ 50% of predicted.
• Karnofsky performance status \> 60.
• Graft source of peripheral blood (the infused cluster of differentiation 34 (CD34)+ cell dose will be capped at 5 x 10\^6 CD34+ cells/kg recipients actual body weight) or bone marrow (the ideal infused total nucleated cell dose (TNC) will be targeted at 4 x 10\^8/kg recipient actual body weight).
• A negative pregnancy test will be required for all women of child bearing potential. Females of child bearing potential should agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug and must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, or agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\] and withdrawal are not acceptable methods of contraception.). Breast-feeding is not permitted.
• Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following: practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, or must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, or agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception.)
• No evidence of uncontrolled bacterial, viral or fungal infections at the time of enrollment.
• Transplant recipient able to give informed consent. \* Patients must be human leukocyte antigen (HLA) typed at high resolution using DNA based typing at the following HLA loci: HLA-A, -B, -C and DRB1 and have available: A related haploidentical bone marrow donor with two, three or four HLA-mismatches. A unidirectional mismatch in either the graft-versus-host or host-versus-graft direction is considered a mismatch. The donor and recipient must be HLA identical for at least one antigen (using high-resolution DNA-based typing) at the following genetic loci: HLA-A, HLA-B, HLA-C, and HLA-DRB1. Fulfillment of this criterion shall be considered sufficient evidence that the donor and recipient share one HLA haplotype, and typing of additional family members is not required.

You may not qualify if:

• Patient must not have a healthy, eligible and readily available HLA-identical sibling donor or a volunteer adult unrelated donor (matched at allele-level at HLA-A, -B, -C and -DRB1).
• No serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.\\
• Presence of active disease in acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS): patients with active disease defined as \>5% blasts in bone marrow and/or circulating leukemic blasts in peripheral blood, patients with known active central nervous disease involvement with leukemia/lymphoma or lymphoma patients with progressive disease on clinical and/or radiographic assessment are not eligible for this study.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (2)

• Van Besien K, Devine S, Wickrema A, Jessop E, Amin K, Yassine M, Maynard V, Stock W, Peace D, Ravandi F, Chen YH, Hoffman R, Sossman J. Regimen-related toxicity after fludarabine-melphalan conditioning: a prospective study of 31 patients with hematologic malignancies. Bone Marrow Transplant. 2003 Sep;32(5):471-6. doi: 10.1038/sj.bmt.1704166.

  PMID: 12942092 BACKGROUND

• Brammer JE, Khouri I, Gaballa S, Anderlini P, Tomuleasa C, Ahmed S, Ledesma C, Hosing C, Champlin RE, Ciurea SO. Outcomes of Haploidentical Stem Cell Transplantation for Lymphoma with Melphalan-Based Conditioning. Biol Blood Marrow Transplant. 2016 Mar;22(3):493-8. doi: 10.1016/j.bbmt.2015.10.015. Epub 2015 Oct 20.

  PMID: 26497906 BACKGROUND

MeSH Terms

Conditions

Hematologic Neoplasms; Multiple Myeloma; Hematologic Diseases

Interventions

Melphalan; fludarabine; fludarabine phosphate; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hemic and Lymphatic Diseases; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Radiotherapy; Therapeutics; Investigative Techniques

Results Point of Contact

• Title: Mehdi Hamadani, MD
• Organization: Medical College of Wisconsin

mhamadani@mcw.edu

414-805-4600

Study Officials

• Mehdi Hamadani

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Medicine, Division of Hematology/Oncology

Model Details: 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.

Study Record Dates

• First Submitted: May 17, 2017
• First Posted: May 19, 2017
• Study Start: December 8, 2017
• Primary Completion: November 12, 2024
• Study Completion: December 8, 2025
• Last Updated: January 27, 2026
• Results First Posted: January 27, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)