Clinical Research of Pomalidomide Maintenance Therapy for Primary Multiple Myeloma

Sponsor

LanZhou University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05378971

Collaborator

Beijing Health Alliance Charitable Foundation (Other)

Enrollment

Location

Arm

36.5

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The trial is a single-center, single-arm, prospective clinical study with a planned enrollment of 15 patients with primary Multiple myeloma(MM), aiming to investigate the efficacy and safety of maintenance therapy with Pomalidomide in patients with primary MM. Patients enrolled were divided into two categories: 1) patients suitable for Autologous Hematopoietic Stem Cell Transplantation(ASCT) started pomalidomide maintenance therapy 3 months after ASCT; 2) patients not suitable for ASCT started pomalidomide maintenance therapy after induction and consolidation therapy to achieve maximum efficacy. Dosing on days 1-21, 2 mg daily for 28 days as a cycle, for a total duration of 36 months or the onset of disease progression, intolerable adverse events. 2-year progression-free survival (2y-PFS) was used as the primary study endpoint, 2-year overall survival (2y-OS), complete remission rate (CR), very good partial remission rate (VGPR), and negative rate of minimal residual disease(MRD) were secondary study endpoints, and the incidence of adverse events (AEs) was assessed.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Pomalidomide	N/A

Detailed Description

Maintenance regimens based on thalidomide and lenalidomide have been shown in numerous clinical trials to significantly improve PFS in patients, but the use of thalidomide is limited by adverse effects such as peripheral neurotoxicity and post-relapse drug resistance. Pomalidomide is a third-generation immunomodulator with a similar structure to thalidomide and lenalidomide, but with stronger anti-MM activity and a similar safety profile. The known mechanisms of action include (1) immunomodulatory effects (2) direct antitumor effects (3) anti-angiogenic activity. (4) Effects on the bone marrow microenvironment. The most common toxicities of pomalidomide include bone marrow suppression, skin reactions, gastrointestinal reactions, and infections, etc. Peripheral neuropathy is less common than thalidomide, and the incidence of thromboembolism is <5%. Pomalidomide is currently used mainly in the treatment of relapsed refractory adult MM, and exploration in post-ASCT maintenance therapy is currently ongoing (NCT01745588). Several retrospective analyses suggest that low-dose pomalidomide may have potential in the maintenance treatment of patients with MM. Therefore, investigators developed a maintenance regimen of low-dose pomalidomide to assess the value of maintenance therapy in MM patients who underwent ASCT or who were not suitable for ASCT. Such regimens may reduce drug toxicity and provide greater clinical benefit for patients with MM.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Patients enrolled were divided into two categories: 1) patients suitable for Autologous Hematopoietic Stem Cell Transplantation(ASCT) started pomalidomide maintenance therapy 3 months after ASCT; 2) patients not suitable for ASCT started pomalidomide maintenance therapy after induction and consolidation therapy to achieve maximum efficacy. Dosing on days 1-21, 2 mg daily for 28 days as a cycle, for a total duration of 36 months or the onset of disease progression, intolerable adverse events.Patients enrolled were divided into two categories: 1) patients suitable for Autologous Hematopoietic Stem Cell Transplantation(ASCT) started pomalidomide maintenance therapy 3 months after ASCT; 2) patients not suitable for ASCT started pomalidomide maintenance therapy after induction and consolidation therapy to achieve maximum efficacy. Dosing on days 1-21, 2 mg daily for 28 days as a cycle, for a total duration of 36 months or the onset of disease progression, intolerable adverse events.

Masking:

None (Open Label)

Masking Description:

Subjects and researchers can know which treatment is being used.

Primary Purpose:

Treatment

Official Title:

Clinical Research of Pomalidomide Maintenance Therapy for Primary Multiple Myeloma

Actual Study Start Date :

May 15, 2022

Anticipated Primary Completion Date :

May 30, 2025

Anticipated Study Completion Date :

May 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: experimental group Primary MM patients started maintenance therapy after 3 months of ASCT or after maximum efficacy was achieved with induction and consolidation therapy. All patients will receive pomalidomide 1 mg daily on days 1 through 21 of each 28-day cycle.	Drug: Pomalidomide Pomalidomide, 2mg/d, d1-21; treatment cycles every 28days Other Names: Pomalyst

Arm

Intervention/Treatment

Experimental: experimental group

Primary MM patients started maintenance therapy after 3 months of ASCT or after maximum efficacy was achieved with induction and consolidation therapy. All patients will receive pomalidomide 1 mg daily on days 1 through 21 of each 28-day cycle.

Drug: Pomalidomide

Pomalidomide, 2mg/d, d1-21; treatment cycles every 28days

Other Names:

Pomalyst

Outcome Measures

Primary Outcome Measures

2-year progression-free survival(2y-PFS) [up to 24 months.]
2y-PFS was defined as the proportion of patients who reached at least 2 years from the first day of treatment to the time of disease progression or death.

Secondary Outcome Measures

2-year overall survival(2y-OS) [up to 24 months.]
2y-OS was defined as the proportion of patients with a time from the first day of treatment to death of at least 2 years.
Complete remission(CR) [up to 24 months.]
It includes strict complete remission (sCR), CR: negative serum and urine immunofixation electrophoresis and bone marrow plasma cells <5%; sCR: normal serum free light chain ratio and absence of clonal plasma cells in bone marrow confirmed by immunohistochemistry on the basis of meeting CR criteria;
very good partial remission(VGPR) [up to 24 months.]
VGPR: undetectable M protein by serum protein electrophoresis but still positive by serum and and urine immunofixation electrophoresis, or ≥90% reduction in M protein and urine M protein <100 mg/24h.
negative rate of minimal residual disease [up to 24 months.]
Flow cytometry was used to detect cells with abnormal immunophenotype, and residual tumor cells <10-4 were considered negative.
adverse events [Adverse event reports are collected once a month during treatment, up to 24 months.]
number of participants with treatment-related adverse events as assessed by CTCAE 5.0

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subject diagnosed as initially diagnosed with symptomatic MM by the diagnostic criteria of International Myeloma Working Group(IMWG), aged ≥ 18 years.
Subject undergoing ASCT who have had prior induction therapy for no more than 12 months and whose disease has not progressed within 3 months of ASCT.
Subject who are not candidates for ASCT have reached maximum efficacy after induction and consolidation therapy.
Eastern Cooperative Oncology Group (ECOG) physical status score of 0-3.
Serum transaminase levels less than three times the upper limit of normal, serum total bilirubin levels not exceeding 35 umol/L, serum creatinine levels less than 177 umol/L, absolute neutrophil values greater than 1.0 x 10^{9/L, and platelet counts
greater than 75 x 10}9/L.
Subject of childbearing potential must use two reliable methods of contraception simultaneously or have absolutely no sexual relations with the opposite sex for 4 weeks prior to initiation of treatment, during treatment, during suspension of dosing and for 4 weeks after termination of treatment, and women of childbearing potential agree to perform monthly pregnancy tests until 4 weeks after discontinuation of study drug.
Subject voluntarily enrolled in this study and signed an informed consent form.

Exclusion Criteria:

Subject has 17p-, 1q21 amplification, t(4;14), t(14;16), t(14;20), t(11;14), and p53 mutation.
Subject who, in the judgment of the investigator, cannot tolerate pomalidomide treatment or are allergic to lenalidomide or thalidomide drugs.
Subject with a diagnosis of nonsecretory MM (meaning subjects with completely nonsecretory MM or subjects with a small amount of free light chain but with less than 100 mg/L of affected light chain).
with central nervous system involvement.
subject with peripheral neuropathy ≥ grade 3.
subject with known active hepatitis B virus (HBV-DNA ≥ l × 103 copies/mL or HBV-DNA > 200 IU/mL) or hepatitis C virus (HCV), or serologically positive for human immunodeficiency virus (HIV).
Subject with concurrent other neoplasms or a prior history of neoplasms or antineoplastic therapy (including major surgery) within the last 4 weeks, except for the following neoplastic diseases or those who have lived tumor-free for ≥ 3 years to date: basal cell carcinoma of the skin, squamous epithelial cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, incidental histologic findings of prostate cancer (TNM clinical stage of T1a or T1b) or treated prostate cancer.
Subject with coexisting serious infectious disease.
Subject who refuse to use a reliable form of contraception during pregnancy and lactation or at an appropriate age.
Subject with active new thrombosis or unwilling to undergo antithrombotic therapy.
Subject who, in the opinion of the investigator, are not suitable for enrollment.