Clinical Study of Safety and Tolerability of Melphalan Hydrochloride for R/R MM

Clinical Study of Safety and Tolerability of Melphalan Hydrochloride for Injection in the Treatment of Relapsed or Relapsed and Refractory Multiple Myeloma

This study is an investigator-initiated clinical study to evaluate the safety and tolerability of melphalan hydrochloride for injection in patients with relapsed or relapsed refractory multiple myeloma. Using the "3 + 3" dose escalation principle, 3-6 subjects per dose were enrolled, depending on the dose limiting toxicity (DLT) observed in the first cycle of chemotherapy for each subject. After completing the 21-day assessment of the first cycle of chemotherapy, if there was no DLT, the study started for the next dose group.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: melphalan hydrochloride for injection

Detailed Description

The escalation method was as follows: 1 subject in each dose group was evaluated for safety by the investigator, and another 2 subjects were evaluated with the permission of the investigator: if none of them experienced DLT, they were escalated to the next dose group.If 1 subject experiences DLT, another 3 subjects will be enrolled in the same dose group.If DLT is not observed in 3 newly added subjects, the study of the next dose group can be started.Dose escalation was terminated if 2 or more DLTs were observed in 3 subjects enrolled in each dose group, or 1 or more DLTs were observed in 3 additional subjects per group.This dose was judged as "intolerable dose", and dose escalation was stopped at the same time. The previous dose group was used as MTD. If only 3 patients were enrolled in the previous dose group, 3 more patients were required (the continued dose escalation should be less than"intolerable dose"). DLT was continued to be observed to determine MTD. Dose escalation for the same subject was not permitted.If a subject dropped out during the DLT observation period due to non-DLT reasons or did not complete DLT observation according to the protocol, continued enrollment of subjects is required to meet the requirement of 3 or 6 subjects per dose. The administration method is as follows: Melphalan Hydrochloride for Injection 9 mg/m2, 18 mg/m2, 27 mg/m2 and 40 mg/m2 (if there is no DLT in this dose group when the dose is up to 40 mg/m2).The primary objective of this phase is to determine the optimal dose of melphalan hydrochloride for injection, up to 40 mg/m2.

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yang Liu; Phone Number: +86-13716926210; Email: pkuphliuyang@bjmu.edu.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Recruiting
      • Peking University People's Hospital
      • Contact: Yang Liu; Phone Number: +8613716926210; Email: pkuphliuyang@bjmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years old, male or female;
2. Relapsed or refractory multiple myeloma according to IMWG. There is no requirement for the number of previous treatment lines in this study
3. With any one of the following measurable indicators: serum protein electrophoresis (SPEP) ≥ 1 g/dL (10 g/L), if IgA, IgD, IgE or IgM multiple myeloma subjects, ≥ 0.5 g/dL (≥ 5 g/L); urine M protein ≥ 200 mg/24h; serum free light chain (FLC) ≥ 10 mg/dL and abnormal serum free light chain kappa/lambda ratio;
4. Life expectancy ≥ 6 months;
5. ECOG score ≤ 2;
6. ECG QT interval ≤ 470 ms;
7. Neutrophil ≥ 1.0*10^9/L, platelet ≥ 75*10^9/L (or 50 *10^9/L if plasma cell infiltration in bone marrow more than 50%);
8. Tbil ≤1.5 ULN，AST and ALT≤3.0 ULN （Gilbert syndrome except);
9. eGFR ≥ 45 ml/min or creatinine ≤ 2mg/dl
10. Understand the contents of this study and have signed the informed consent form.

Exclusion Criteria:

1. primary amyloidosis, MGUS, or smoldering multiple myeloma or plasma cell leukemia (according to the World Health Organization criteria: peripheral blood ≥ 5%) or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin) ;
2. primary refractory disease (i.e., no at least MR response to any prior therapy);
3. combined clinically significant comorbidities (investigator judged);
4. the presence of active infection;
5. history of other malignant tumors (except multiple myeloma) within 3 years before signing the informed consent;
6. Pregnant or lactating women;
7. radiotherapy or other anti-myeloma treatment within 14 days before signing the informed consent;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: melphalan hydrochloride for injection; Drug Name: melphalan hydrochloride The dosage of different dosage groups were: 9 mg/m2; 18 mg/m2; 27 mg/m2; 40 mg/m2 Administration frequency: once for each subject	Drug: melphalan hydrochloride for injection; Intravenous (iv) infusion for 20 minutes on Day 1 of a 21-day chemotherapy cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose limiting toxicity (DLT)	Hematological toxicity: Grade 4 thrombocytopenia OR Grade 4 neutropenia more than 7 days; Any non - hematological toxicity of grade 3 or above, except: 1) Grade 3 nausea / vomiting or diarrhea with duration less than 72 hours; 2) Grade 3 fatigue with duration less than one week; Grade 3 fever; Grade 4 infusion reaction;	one month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The overall response rate	Hematological response CR + VGPR + PR +MR	one month
TTP	Time to progression	12 months
Progression-Free Survival (PFS)	PFS is defined as the time from drug administration to progression or death, whichever occurs first	12 months
Overall Survival (OS)	OS is defined as the time from drug administration to death.	12 months

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Collaborators: CASI Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Jin Lu, Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2022
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: June 26, 2022
• First Submitted That Met QC Criteria: June 26, 2022
• First Posted (Actual): June 30, 2022

Study Record Updates

• Last Update Posted (Actual): April 14, 2023
• Last Update Submitted That Met QC Criteria: April 13, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Melphalan
• Other Study ID Numbers: 2021PHD013-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes