Maintenance treatment with ixazomib for newly diagnosed mantle cell lymphoma

Multicenter Phase II Study of Ixazomib Maintenance in Patients With Newly Diagnosed Mantle Cell Lymphoma

This study is testing if taking ixazomib as a maintenance treatment can help people with newly diagnosed mantle cell lymphoma stay in remission after their initial chemotherapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 98 (estimated)
• Ages: 19 Years and up
• Sex: All
• Sponsor: Kosin University Gospel Hospital (Academic / other)
• Drugs / interventions: chemotherapy, Rituximab, Cyclophosphamide, Doxorubicin, Prednisone
• Locations: 1 site (Busan, Western)
• Trial ID: NCT03616782 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of ixazomib as a maintenance therapy in patients with newly diagnosed mantle cell lymphoma (MCL) who have shown a partial response or better after receiving induction chemotherapy (RCHOP or VR-CAP). Following induction therapy, eligible patients will begin ixazomib treatment at least 8 weeks post-chemotherapy, taking the drug orally on specified days for up to 24 months, with potential dose escalation based on response. The study aims to assess the safety and efficacy of this approach in prolonging remission and improving patient outcomes.

Who should consider this trial

Good fit: Ideal candidates include adults aged 19 and older with histologically confirmed mantle cell lymphoma who have achieved a partial response or better after induction chemotherapy.

Not a fit: Patients with central nervous system involvement by lymphoma or those who have not responded adequately to induction chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve remission duration and overall survival for patients with mantle cell lymphoma.

How similar studies have performed: While there have been studies on maintenance therapies for lymphoma, the specific use of ixazomib in this context is relatively novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Male or female patients aged ≥19 years
2. Histologically confirmed mantle cell lymphoma (MCL) meeting the following criteria: determined by histology and either expression of cyclin D1 (in association with CD20 and CD5) or evidence of t(11;14) translocation (by cytogenetics, fluorescence in-situ hybridization, or polymerase chain reaction)
3. In all patients, a paraffin-embedded biopsy tissue block or slides (preferably of lymph node origin or bone marrow) was sent to central laboratories (Diagnostic Cytology Laboratories or department of pathology) for confirmation of diagnosis of MCL.
4. Stage II, III, or IV
5. Patients who received RCHOP or VR-CAP induction chemotherapy for 6 cycles confirmed response as more than PR or PR after induction therapy and who are ineligible for transplantation. .
6. No clinical evidence of central nervous system (CNS) involvement by lymphoma
7. Patients must have measurable disease; CT scans at baseline are required to define the extent of measurable disease; the scans must be obtained within 6 weeks prior to registration; combined CT/PET scans may be used for the baseline and subsequent evaluations if accurate tumor measurements can be obtained from the CT component
8. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
9. Absolute neutrophil count (ANC) \> 1,000 mm\^3 (unless low count due to marrow involvement or splenomegaly)
10. Platelets \> 75,000 mm\^3 (unless low counts due to marrow involvement or splenomegaly)
11. Creatinine clearance of ≥ 30 mL/min
12. Total bilirubin ≤ 1.5 x the upper limit of normal (may be up to 3.0 mg/dL if due to Gilbert's disease or due to liver involvement by lymphoma), alanine transaminase level ≤3 times the upper limit of normal; aspartate transaminase level ≤3 times the upper limit of normal
13. Patients over the age of 45 must have a left ventricular ejection fraction (LVEF) of greater than 45% documented within 90 days prior to registration
14. Female patients had to be post-menopausal for ≥1 year, surgically sterile, or practicing an effective method of birth control (as described in the protocol), and have a negative serum beta-human chorionic gonadotropin or urine pregnancy test at screening; they also had to agree to continue using birth control measures for ≥6 months after terminating treatment. Male patients had to agree to use an acceptable method of contraception for the duration of the study.

Exclusion Criteria:

1. Female patients who are lactating or have a positive serum pregnancy test during the screening period.
2. Grade 2 or higher baseline peripheral neuropathy
3. Major surgery within 14 days before enrollment.
4. Radiotherapy within 14 days before enrollment. If the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the ixazomib.
5. Central nervous system involvement.
6. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment.
7. Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
8. Systemic treatment, within 14 days before the first dose of ixazomib, with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John's wort.
9. Active systemic infection requiring treatment, a known diagnosis of human HIV, or active hepatitis B (hepatitis B carriers were permitted)
10. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
11. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
12. Known gastrointestinal(GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing.
13. Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
14. Patient has more than Grade 2 peripheral neuropathy on clinical examination during the screening period.
15. Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial.
16. Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not.

Where this trial is running

Busan, Western

• Kosin University Gospel Hospital — Busan, Western, South Korea (Recruiting)

Study contacts

• Principal investigator: Ho Sup Lee, MD — Kosin University Gospel Hospital
• Study coordinator: Ho Sup Lee, MD

Conditions Mantle Cell Lymphoma