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

Primary Purpose

Multiple Myeloma

Status

Recruiting

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

melphalan hydrochloride for injection

About this trial

This is an interventional treatment trial for Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age ≥ 18 years old, male or female;
Relapsed or refractory multiple myeloma according to IMWG. There is no requirement for the number of previous treatment lines in this study
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;
Life expectancy ≥ 6 months;
ECOG score ≤ 2;
ECG QT interval ≤ 470 ms;
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%);
Tbil ≤1.5 ULN，AST and ALT≤3.0 ULN （Gilbert syndrome except);
eGFR ≥ 45 ml/min or creatinine ≤ 2mg/dl
Understand the contents of this study and have signed the informed consent form.

Exclusion Criteria:

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) ;
primary refractory disease (i.e., no at least MR response to any prior therapy);
combined clinically significant comorbidities (investigator judged);
the presence of active infection;
history of other malignant tumors (except multiple myeloma) within 3 years before signing the informed consent;
Pregnant or lactating women;
radiotherapy or other anti-myeloma treatment within 14 days before signing the informed consent;

Sites / Locations

Peking University People's HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

melphalan hydrochloride for injection

Arm Description

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

Outcomes

Primary Outcome Measures

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;

Secondary Outcome Measures

The overall response rate

Hematological response CR + VGPR + PR +MR

TTP

Time to progression

Progression-Free Survival (PFS)

PFS is defined as the time from drug administration to progression or death, whichever occurs first

Overall Survival (OS)

OS is defined as the time from drug administration to death.

Full Information

NCT ID

NCT05438394

First Posted

June 26, 2022

Last Updated

April 13, 2023

Sponsor

Peking University People's Hospital

Collaborators

CASI Pharmaceuticals, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT05438394

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Recruiting

Study Start Date

October 13, 2022 (Actual)

Primary Completion Date

December 31, 2023 (Anticipated)

Study Completion Date

December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Peking University People's Hospital

Collaborators

CASI Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Myeloma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Model Description

Four dose groups. Using the "3 + 3" dose escalation principle, 3-6 subjects per dose group, according to 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.

Masking

None (Open Label)

Allocation

N/A

Enrollment

24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

melphalan hydrochloride for injection

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

melphalan hydrochloride for injection

Intervention Description

Intravenous (iv) infusion for 20 minutes on Day 1 of a 21-day chemotherapy cycle

Primary Outcome Measure Information:

Title

Dose limiting toxicity (DLT)

Description

Time Frame

one month

Secondary Outcome Measure Information:

Title

The overall response rate

Description

Hematological response CR + VGPR + PR +MR

Time Frame

one month

Title

TTP

Description

Time to progression

Time Frame

12 months

Title

Progression-Free Survival (PFS)

Description

PFS is defined as the time from drug administration to progression or death, whichever occurs first

Time Frame

12 months

Title

Overall Survival (OS)

Description

OS is defined as the time from drug administration to death.

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age ≥ 18 years old, male or female; Relapsed or refractory multiple myeloma according to IMWG. There is no requirement for the number of previous treatment lines in this study 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; Life expectancy ≥ 6 months; ECOG score ≤ 2; ECG QT interval ≤ 470 ms; 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%); Tbil ≤1.5 ULN，AST and ALT≤3.0 ULN （Gilbert syndrome except); eGFR ≥ 45 ml/min or creatinine ≤ 2mg/dl Understand the contents of this study and have signed the informed consent form. Exclusion Criteria: 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) ; primary refractory disease (i.e., no at least MR response to any prior therapy); combined clinically significant comorbidities (investigator judged); the presence of active infection; history of other malignant tumors (except multiple myeloma) within 3 years before signing the informed consent; Pregnant or lactating women; radiotherapy or other anti-myeloma treatment within 14 days before signing the informed consent;

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Yang Liu

Phone

+86-13716926210

pkuphliuyang@bjmu.edu.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jin Lu

Organizational Affiliation

Peking University People's Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Peking University People's Hospital

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100044

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yang Liu

Phone

+8613716926210

pkuphliuyang@bjmu.edu.cn

First Name & Middle Initial & Last Name & Degree

Jin Lu

12. IPD Sharing Statement

Plan to Share IPD

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

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