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

Sponsor
Peking University People's Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT05438394
Collaborator
CASI Pharmaceuticals, Inc. (Industry)
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Study Details

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: melphalan hydrochloride for injection
Phase 1

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 Design

Study Type:
Interventional
Anticipated Enrollment :
24 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention 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.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)
Primary Purpose:
Treatment
Official Title:
Clinical Study of Safety and Tolerability of Melphalan Hydrochloride for Injection in the Treatment of Relapsed or Relapsed and Refractory Multiple Myeloma
Actual Study Start Date :
Jun 26, 2022
Anticipated Primary Completion Date :
Jan 31, 2023
Anticipated Study Completion Date :
Dec 31, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

  1. Dose limiting toxicity (DLT) [one month]

    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

  1. The overall response rate [one month]

    Hematological response CR + VGPR + PR +MR

  2. TTP [12 months]

    Time to progression

  3. Progression-Free Survival (PFS) [12 months]

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

  4. Overall Survival (OS) [12 months]

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

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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 ≥ 1.010^9/L, platelet ≥ 75109/L (or 50 *109/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;

Contacts and Locations

Locations

Site City State Country Postal Code
1 Peking University People's Hospital Beijing Beijing China 100044

Sponsors and Collaborators

  • Peking University People's Hospital
  • CASI Pharmaceuticals, Inc.

Investigators

  • Principal Investigator: Jin Lu, Peking University People's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
JinLu, Professor, Peking University People's Hospital
ClinicalTrials.gov Identifier:
NCT05438394
Other Study ID Numbers:
  • 2021PHD013-001
First Posted:
Jun 30, 2022
Last Update Posted:
Jun 30, 2022
Last Verified:
Jun 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
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
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jun 30, 2022