Primary Multiple Myeloma Who Achieved MRD Negativity After Induction Therapy, ASCT or Not

NCT ID: NCT06463717

Last Updated: 2024-06-24

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 210 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-12-01
• Study Completion Date: 2028-12-31

Brief Summary

The goal of this observational study is to compare the efficacy and safety of autologous hematopoietic stem-cell transplantation (ASCT) versus non ASCT regimens in primary multiple myeloma patients achieved MRD negativity after induction.

The main question it aims to answer is:

In primary multiple myeloma patients who achieved MRD negativity after induction, non ASCT regimens are not inferior to ASCT or not? Participants will receive ASCT or non ASCT regimen according to their own choice.

Researchers will compare ASCT and non ASCT group see if any significant difference in efficacy and safety.

Detailed Description

Background Multiple myeloma (MM) is third most common hematological malignancy. For newly diagnosed MM patients who are transplantation eligible, the current standard treatment regimen is induction therapy with bortezomib plus lenalidomide plus dexamethasone (VRD), high-dose melphalan (200 mg/m2) followed by autologous stem cell transplantation (MEL200-ASCT), and maintenance therapy with lenalidomide and/or proteasome inhibitors. However, MEL200-ASCT requires hospitalization and may induces toxic side effects. In recent years, multiple MM international research centers have explored and compared the efficacy of different treatment regimens (such as bortezomib plus melphalan plus prednisone, bortezomib plus lenalidomide plus dexamethasone, carfilzomib plus cyclophosphamide plus dexamethasone, and carfilzomib plus lenalidomide plus dexamethasone) with MEL200-ASCT, and found that MEL200-ASCT has a higher progression free survival compared to the aforementioned chemotherapy regimens, but failed to show benefit in overall survival. The advantage of MEL200-ACT in progression free survival can be attributed to its ability to achieve deeper therapeutic responses compared to chemotherapy regimens, including a higher complete response (CR), very good partial response (VGPR), and a higher negative rate for minimal residual disease (MRD) or sustained negative rate for MRD.

MRD was introduced by the International Myeloma Working Group in 2016, which implies deeper clinical response than CR and can be detected by flow cytometry or second-generation sequencing, with a sensitivity of at least 10-5. Research has shown that MRD is the most powerful prognostic factor for MM, and MM patients with negative MRD have a significant superior survival than MRD positive patients. As mentioned earlier, MEL200-ASCT induces deeper therapeutic response than chemotherapy, and results in superior progression survival. So, in patients who have already reached MRD negative after VRD induction treatment, does MEL200-ASCT still have an advantage in progression free survival compared to chemotherapy? A study comparing the efficacy of MEL200-ASCT with carfilzomib plus cyclophosphamide and dexamethasone found that among patients with detectable MRD after induction therapy, MEL200-ASCT group had a higher progression free survival rate than chemotherapy. However, there was no evidence suggesting that MEL200-ASCT is beneficial for patients who have already obtained MRD negative after induction therapy.

Therefore, this study aims to investigate the status of MEL200-ACT in newly diagnosed MM patients who have achieved MRD negative after induction therapy with the current standard protocol.

Data collection Patient who met the enrollment criteria is unselected recorded and followed regularly.

Sample size calculation This study aims to demonstrate that non ASCT regimens is not inferior to high dose melphalan followed by ASCT in terms of progression free survival in MM patients who already obtained MRD negative after induction therapy. Based on available date, 2-year progression free survival rate was 85% for patients received MRD negativity after induction therapy and followed by ASCT. Therefore, the investigators assure that 2-year progression free survival rate of non ASCT regimen group should not be less than 75%, i.e. a non-inferiority margin of 10%. Using a one-sided non-inferiority test for two exponential survival curves with 0.025 alpha, 0.8 power, a common exponential dropout rate of 10% and number of non ASCT and ASCT patients in a 3:2 ratio, 126 patients for non ASCT and 84 patients for ASCT group are required.

Conditions

Multiple Myeloma; Minimal Residual Disease

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

ASCT regimen

Primary multiple myeloma patients who receive autologous hematopoietic stem-cell transplantation (ASCT) after they achieved MRD negativity after induction

Transplant, Autologous

Intervention Type: DRUG

High-dose melphalan followed by autologous stem cell transplantation

non ASCT regimen

Primary multiple myeloma patients who receive non autologous hematopoietic stem-cell transplantation (ASCT) regimen such as 4-6 cycles of bortezomib-lenalidomide-dexamethasone after they achieved MRD negativity after induction

Chemotherapy drug

Intervention Type: DRUG

Regimen such as Bortezomib plus Lenalidomide plus Dexamethasone

Interventions

Transplant, Autologous

High-dose melphalan followed by autologous stem cell transplantation

Intervention Type: DRUG

Chemotherapy drug

Regimen such as Bortezomib plus Lenalidomide plus Dexamethasone

Intervention Type: DRUG

Other Intervention Names

ASCT; Non ASCT regimen

Eligibility Criteria

Inclusion Criteria

1. Newly diagnosed multiple myeloma according to the criteria of International Working Group of Myeloma

2. Age ranges from 18-70 years old

3. Achieved MRD negativity and at least very good partial response in clinical response after 4-6 courses of induction therapy. MRD is measured by MRD by multicolor flow with a sensitivity of 10-5.

4. At enrollment, score of Eastern Cooperative Oncology Group (ECOG) should be 0-2.

5. Organ function requirement: Blood bilirubin ≤ 2mg/dL (35 μ mol/L), Alanine aminotransferase/Aspartate aminotransferase below 2 times the upper limit of normal value, Creatinine clearance rate (Ccr) ≥ 30ml/min and Cardiac ejection fraction ≥50%.

6. Expected survival more than 3 months.

Exclusion Criteria

1. Two or more high-risk cytogenetic abnormalities, including del (17p), t (4; 14), t (14; 16), del (1p), amp (1q). Fluorescence in situ hybridization was used to analyze CD138 positive sorted cells, with cut off value of 15% for translocation, 10% for deletion, and amp (1q) of 20%.

2. Extracellular plasma cell disease, central invasion of myeloma, plasma cell leukemia

3. History of other malignant tumors within the past 5 years

4. Patients with HIV, active tuberculosis, clinically active hepatitis A, B, or C

5. Other serious condition that may restrict patients from continuing treatment (such as advanced infection, uncontrolled diabetes, severe cardiac insufficiency, or angina pectoris)

6. General condition not suitable for chemotherapy

7. Pregnant or lactating women

8. Suffering from other serious organic diseases and mental disorders.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

First Affiliated Hospital of Wenzhou Medical University

OTHER

Sponsor Role: collaborator

The Affiliated Hospital of Medical College, Ningbo University

OTHER

Sponsor Role: collaborator

Dongyang People's Hospital

OTHER

Sponsor Role: collaborator

First Affiliated Hospital of Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Haitao Meng

Role: PRINCIPAL_INVESTIGATOR

Zhejiang University

Locations

The First Affiliated Hospital of Zhejiang University

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Liangshun You

Role: CONTACT

youliangshun@zju.edu.cn

+86 15088687797

Qiumei Yao

Role: CONTACT

qiumei_yao@163.com

+86 13867490514

Facility Contacts

Liangshun You

Role: primary

youliangshun@zju.edu.cn

+86 15088687797

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Other Identifiers

IIT20230339B-R1

Identifier Type: -

Identifier Source: org_study_id