Evaluate Safety and Efficacy of High-dose Melphalan HCL for Injection in MM Patients With Auto-HSC Transplantation

NCT06425276 | Completed Phase 4 FDA Drug

• 1 other identifier: EVOM-CL-001
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if high-dose Melphalan HCl for Injection works to treat multiple myeloma. It will also learn about the safety of high dose Melphalan HCl for Injection. The main questions it aims to answer are: Does high-dose Melphalan HCl for Injection deplete bone marrow activity which results in a better outcome of patients'own stem cell (blood-forming cell) transplantation? What medical problems do participants have when taking high-dose Melphalan HCl for Injection? How fast is the high-dose Melphalan HCl for Injection cleared out from blood? Participants will:

• Take high-dose Melphalan HCl for Injection for 2 days
• Have stem cell transplantation one day after treatment
• Stay in the hospital for at least 10days and visit the clinic once every week for the first month after transplantation and every month after for checkups and tests.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (6)

• Rate of patients achieveing myeloablation

  To record the percentage of patients who achieve myeloablation which is defined as absolute neutrophil count \[ANC\] \<0.5 × 109/L, absolute lymphocyte count \[ALC\] \<0.1 × 109/L, or platelet count \<20,000/mm3 in 2 consecutive daily assessments.

  95±5 days after ASCT

• Time to achieveing myeloablation

  To record the time, in days, from the date of first dose of High-dose Melphalan HCL for Injection to the date of myoloablation which is defined as absolute neutrophil count \[ANC\] \<0.5 × 109/L, absolute lymphocyte count \[ALC\] \<0.1 × 109/L, or platelet count \<20,000/mm3 in 2 consecutive daily assessments.

  95±5 days after ASCT

• Time to achieveing neutrophil engraftment

  To record the time, in days, from the date of Auto-HSCT to the date when absolute neutrophil count (ANC) \>0.5 × 109/L in 3 consecutive daily assessments.

  95±5 days after ASCT

• Time to achieving platelet engraftment

  To record the time, in days, from the date of Auto-HSCT to the date when untransfused platelet measurement \>20,000/mm3 in 3 consecutive daily assessments.

  95±5 days after ASCT

• Incidence of Treatment-related Motality (TRM)

  To characterize the safety, tolerability of High-dose Melphalan HCL for Myeloablation in MM Patients With Auto-HSC Transplantation by recording the incidence of death without relapse or progression of the disease.

  95±5 days after ASCT

• Incidence and severity of AEs and SAEs, including changes in laboratory values

  To characterize the safety, tolerability of High-dose Melphalan HCL for Injection for Myeloablation in MM Patients With Auto-HSC Transplantation.

  95±5 days after ASCT

Secondary Outcomes (5)

• Overall Response (ORR)

  95±5 days after ASCT

• Tmax of Melphalan HCL for Injection derived from plasma concentrations

  24 Hours

• T1/2 of Melphalan HCL for Injection derived from plasma concentrations

  24 Hours

• Cmax of Melphalan HCL for Injection derived from plasma concentrations

  24 Hours

• AUC of Melphalan HCL for Injection derived from plasma concentrations

  24 Hours

Study Arms (1)

High-dose Melphalan HCl for Injection treatment arm

EXPERIMENTAL

Patients will receive Melphalan HCl for Injection dosed at 100 mg/m2 on Day -3 and Day -2. Following 1 day of rest after the myeloablative conditioning (Day -1), patients will receive an autologous graft with a minimum cell dose of 2 × 106 CD34+ cells/kg of patient body weight (Day 0).

Drug: Melphalan Hydrochloride for Injection

Interventions

Melphalan Hydrochloride for Injection DRUG

During the Study Period, patients will receive Melphalan HCl for Injection dosed at 100 mg/m2 on Day -3 and Day -2.

Also known as: Evomela

High-dose Melphalan HCl for Injection treatment arm

Eligibility Criteria

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

You may qualify if:

• Diagnosed as symptomatic multiple myeloma, according to the International Myeloma Working Group's IMWG Guidelines for the Diagnosis and Treatment of Multiple Myeloma, treatment is necessary and suitable for autologous hematopoietic stem cell transplantation;
• When signing the informed consent form, males and females aged ≥ 18 years and ≤ 65 years old;
• Adequate autologous hematopoietic stem cells were collected, defined as peripheral blood stem cells containing at least 2 x 106 CD34+cells/kg that have not been manipulated or refrigerated;
• Important organ functions meet the following conditions:
• i. Echocardiography indicates left ventricular ejection fraction (LVEF) ≥ 40%;
• ii. Serum total bilirubin\<2 times the upper limit of normal value, alanine aminotransferase (ALT) and aspartate aminotransferase (AST)\<3 times the upper limit of normal value;
• Iii. creatinine clearance rate\>60 mL/min ;
• Iv. Blood oxygen saturation\>92% in non oxygenated state, without significant ventilation or ventilation dysfunction;
• The Eastern Oncology Collaborative Group (ECOG) physical fitness status of the subjects is 0, 1, or 2;
• The subject or their legal guardian voluntarily signs an informed consent form approved by the ethics committee before participating in the study, and agrees to complete the entire study treatment according to the clinical trial protocol.

You may not qualify if:

• Multiple myeloma subjects without treatment indications;
• Suffering from plasma cell leukemia;
• Suffering from systemic amyloidosis;
• Subjects with extramedullary plasma cell tumors did not reach PR after induction therapy;
• Suffering from POEMS syndrome (multiple peripheral neuropathy, organ enlargement, endocrine disorders, M-proteinemia, skin changes);
• Suffering from Fahrenheit macroglobulinemia;
• Subjects with non secretory multiple myeloma;
• Subjects with active bacterial, viral, or fungal infections who require oral or intravenous antibiotic treatment according to the researcher's judgment;
• The expected survival period of the subjects is less than 6 months;
• Previously suffering from other malignant tumors, except for cured basal cell carcinoma or cervical carcinoma in situ. Malignant tumors that have undergone curative treatment and achieved complete remission (CR) for more than 5 years can be enrolled. If malignant tumors receive curative treatment but have achieved complete remission (CR) for ≤ 5 years, they cannot be enrolled unless approved by the sponsor;
• Pregnant or lactating women;
• Subjects who have fertility and are unwilling to take appropriate contraceptive measures within 3 months after signing the informed consent form until the end of treatment in this study;
• Positive for human immunodeficiency virus (HIV) antibodies;
• Subjects with positive hepatitis B virus DNA;
• The subject receives other concurrent anti-tumor treatments (including chemotherapy, radiation therapy, hormone therapy, or immunotherapy) within 30 days prior to autologous hematopoietic stem cell transplantation, or plans to receive any such treatments before the last study visit on day 95 ± 5;

Sponsors & Collaborators

• CASI Pharmaceuticals (China) Co., Ltd.: lead

Study Sites (1)

Peking University People's Hospital

Beijing, China

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Melphalan; Injections

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; 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; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Kaiyan Liu

  Peking University People's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2024
• First Posted: May 22, 2024
• Study Start: July 24, 2020
• Primary Completion: July 8, 2021
• Study Completion: September 18, 2021
• Last Updated: May 23, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)