Ixazomib, Lenalidomide, and Combination for Maintenance in NDMM Patients

November 30, 2021 updated by: Junling Zhuang, Peking Union Medical College Hospital

A Multicenter, Open-label, Prospective Study of Ixazomib, Lenalidomide, and Ixazomib in Combination With Lenalidomide for Maintenance Therapy in Patients With Newly Diagnosed Multiple Myeloma

The purpose of this study is to evaluate the real-world efficacy and safety of ixazomib, lenalidomide, or ixazomib in combination with lenalidomide as maintenance therapy in patients with newly diagnosed multiple myeloma in China.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Multiple myeloma (MM), the second most common hematological malignancy, is a clonal plasma cell disorder characterized by the secretion of monoclonal immunoglobulins. The annual incidence of newly diagnosed MM (NDMM) patients is about 2-3/100,000. In the past 20 years, the median overall survival (OS) of MM patients has prolonged from 3 to 5 years to 8 to 10 years since many novel agents developed on the pipeline of treatment. Moreover, multi-drug combination chemotherapy, low-intensity maintenance therapy after achieving a certain effect also contributed to improving the progression-free survival (PFS) and OS in MM patients. Therefore, many international guidelines have explicitly recommended maintenance therapy after first-line regimens until disease progression.

Common maintenance medications include immunomodulatory drugs (IMiDs) such as lenalidomide, thalidomide, ect; proteasome inhibitors (PIs) such as bortezomib. Among them, lenalidomide has the most reliable data as maintenance therapy for prolonging PFS. Although bortezomib maintenance has shown advantages in high-risk MM patients in some clinical trials, it has poor compliance in the real world due to the injection mode of administration and peripheral neuropathy (PN) after long-term use. There is currently no data on the maintenance of large-scale cases in China. The maintenance of regimens in the real world is not standardized, including drug dosage and duration of application. In addition, due to the high cost of bortezomib or lenalidomide for long-term application, domestic thalidomide still accounts for a certain proportion, but its side effects especially PN are very prominent. In addition to the proven efficacy, MM maintenance treatments should preferably include good tolerability, manageable toxicities and administration convenience.

The second-generation PI drug, Ixazomib, was approved in China in May 2018. Based on the data of TOURMALINE MM1 trial and China extended study, ixazomib was approved for the treatment of relapsed and refractory MM. Further more, recent maintenance study after autologous transplantation (MM3) suggested that ixazomib significantly prolonged PFS for 6 months compared with placebo. Because ixazomib is an oral form with a few side effects, especially less PN than bortezomib, safety data and compliance of ixazomib in the real world were comparable as those in the clinical trials.

The survival of patients with multiple myeloma in China is worse than that of western countries. One of the important reasons is irregular follow-up and nonstandard maintenance therapies. Many Chinese MM patients still use traditional maintenance drug thalidomide, which is difficult to apply for a long time due to toxicities especially PN and gastrointestinal reactions. The second generation IMiD drug lenalidomide as maintenance treatment has been increasingly accepted by patients and hematologists. However, due to the low proportion of autologous stem cell transplantation (ASCT) after first-line regimens in China, the efficacy of single-agent maintenance is also limited, especially for high-risk patients. As novel anti-myeloma drugs were rapidly approved and reimbursed in China, a dual oral maintenance regimen of lenalidomide in combination with ixazomib is being explored.

The purpose of this multi-centered study is to evaluate the real world efficacy and safety of the maintenance therapies in Chinese patients with newly diagnosed multiple myeloma (NDMM), which include ixazomib monotherapy, ixazomib combined with lenalidomide, and lenalidomide monotherapy.

Adult NDMM patients who acquire at least partial response (PR) after 4~9 cycles of front-line regimens including ASCT will be recruited. Those who do not reach a PR after 4 cycles of front-line regimens will be switched to the second regimen for at most 5 cycles. After reaching a PR, these patients will also be recruited to the study. Maintenance therapies will be classified into three groups depending on patients' and doctors' discretion, including ixazomib 4mg day 1, 8,15; lenalidomide 25mg qod day 1~21; ixazomib and lenalidomide combination with same doses. Front-line maintenance is given till disease progression. Progression free survival and safety issues will be recorded. Drug doses will be adjusted or withdrawn based on the degree of toxicities.

Adjunctive treatments are prophylaxis of herpes zosters with acyclovir, prophylaxis of venous thrombotic events with aspirin, prophylaxis of high-risk infections with sulfanilamide. The doses of lenalidomide are adjusted depending on clearance of creatinine.

Study Type

Interventional

Enrollment (Anticipated)

180

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100005

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age older than 18 years;
  2. Newly diagnosed MM patients who fulfill the diagnostic criteria of International Myeloma Working Group (IMWG) 2014 standard;
  3. Maintenance treatment will start after first-line treatment or second-line treatment;
  4. The total courses of front-line regimens are between 4-9. Autologous transplantation is considered as consolidation treatment;
  5. The clinical efficacy before the enrollment is partial response (PR) or better;
  6. Physical performance status (ECOG) score ≤ 2;
  7. Patients participate in the study based on his/her own will and voluntarily sign the informed consent form

Exclusion Criteria:

  1. Patients who are allergic or intolerant to ixazomib or lenalidomide;
  2. patients with severe cardiopulmonary dysfunction;
  3. patients with severe hepatic insufficiency, ALT or bilirubin more than 2 times the upper limits of normal range;
  4. patients with other malignancies (except for carcinoma in situ);
  5. patients with serious bacterial or viral infections, such as HIV or HBV, HCV, etc.;
  6. pregnant or lactating women;
  7. can not be strictly contraceptive;
  8. Psychiatric patients and patients with other serious mental illness that potentially impact signing informed consent and disease consultation and follow-up.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Lenalidomide group
lenalidomide 25mg qod d1~21 days, rest 7 days
Drug: Lenalidomide
the lenalidomide group uses lenalidomide as comparitor group and the combination group receives both lenalidomide and ixazomib
Active Comparator: Ixazomib group
ixazomib 4mg orally, once a week, 3 times a month
Drug: Ixazomib
the ixazomib group uses ixazomib as the comparator group, the combination group receives both lenalidomide and ixazomib as the experimental group
Experimental: Combination group
ixazomib 4mg orally, once a week, 3 times a month lenalidomide 25mg qod d1~21 days, rest 7 days use in combination
Drug: Lenalidomide
the lenalidomide group uses lenalidomide as comparitor group and the combination group receives both lenalidomide and ixazomib
Drug: Ixazomib
the ixazomib group uses ixazomib as the comparator group, the combination group receives both lenalidomide and ixazomib as the experimental group

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
progression-free survival
Time Frame: From date of enrollment until the date of first documented progression, assessed up to 20 months
from enrollment to first disease progression
From date of enrollment until the date of first documented progression, assessed up to 20 months
overall survival
Time Frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
from enrollment to death with follow-up
From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
time to next treatment
Time Frame: From date of enrollment until the next treatment, assessed up to 24 months
from enrollment to the time next treatment is administrated
From date of enrollment until the next treatment, assessed up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking Union Medical College Hospital

Collaborators

Peking University First Hospital
The First Affiliated Hospital of Anhui Medical University
Peking University Third Hospital
Jilin Provincial Tumor Hospital
Xuanwu Hospital, Beijing
Beijing Chao Yang Hospital
Tianjin Medical University General Hospital
The First Affiliated Hospital of Shanxi Medical University
Beijing Jishuitan Hospital
Second Hospital of Shanxi Medical University

Investigators

  • Principal Investigator: Junling Zhuang, MD, Peking Union Medical College, department of hematology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 3, 2020

Primary Completion (Anticipated)

October 1, 2022

Study Completion (Anticipated)

October 1, 2022

Study Registration Dates

First Submitted

January 1, 2020

First Submitted That Met QC Criteria

January 3, 2020

First Posted (Actual)

January 6, 2020

Study Record Updates

Last Update Posted (Actual)

December 15, 2021

Last Update Submitted That Met QC Criteria

November 30, 2021

Last Verified

November 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ZS-2129

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

individual baseline characteristic, treatment and follow-up results will be shared after publication

IPD Sharing Time Frame

After publication, the data will become available

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)
  • Clinical Study Report (CSR)
  • Analytic Code

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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