Ixazomib and Rituximab in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma

NCT04047797 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 2018-1090NCI-2019-04857
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well ixazomib and rituximab work in treating patients with mantle cell lymphoma that has come back (relapsed) or does not respond (refractory) to BTK inhibitor treatment. Ixazomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with rituximab may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving ixazomib and rituximab may work better in treating patients with mantle cell lymphoma compared to rituximab alone.

Conditions

Recurrent Mantle Cell Lymphoma; Refractory Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete Remission Rate at 16 Weeks

  Evaluate the complete remission rate of BTK inhibitor refractory MCL patients with ixazomib and rituximab at 16 weeks of therapy. Complete remission at 16 weeks was measured by PET/CT or CT imaging using Lugano Criteria 2014.

  16 weeks

Secondary Outcomes (3)

• Overall Response Rate at 16 Weeks

  16 weeks

• Progression Free Survival (PFS) and Overall Survival (OS)

  16 weeks

• Tolerability of Study Drug at Weeks 8, 16, 28, 42, and 56

  time of first dose of ixazomib through 30 days after the last dose of ixazomib was administered, up to 140 weeks.

Study Arms (1)

Treatment (ixazomib, rituximab)

EXPERIMENTAL

Patients receive ixazomib by mouth on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab IV over 4-8 hours on days 1, 8, 15, and 22 of cycle 1. Beginning in cycle 3, patients receive rituximab Intravenous over 4-8 hours on day 1. Treatment repeats every 28 days up to cycle 12 in the absence of disease progression or unacceptable toxicity. Patients benefiting from treatment may continue to receive ixazomib indefinitely in the absence of disease progression or unacceptable toxicity.

Drug: Ixazomib; Drug: Ixazomib Citrate; Biological: Rituximab

Interventions

Ixazomib DRUG

Given by mouth

Also known as: MLN-2238, MLN2238

Treatment (ixazomib, rituximab)

Ixazomib Citrate DRUG

Given by mouth

Also known as: MLN-9708, MLN9708, Ninlaro

Treatment (ixazomib, rituximab)

Rituximab BIOLOGICAL

Given Intravenous

Also known as: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, rituximab biosimilar TQB2303, rituximab-abbs, RTXM83, Truxima

Treatment (ixazomib, rituximab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed diagnosis of mantle cell lymphoma
• Patients must have measurable disease, as defined by at least one of the following:
• Lymph node or mass 2 cm or greater, splenomegaly \> 13 cm
• Bone marrow only disease as per morphology or flow cytometry
• Patients must have relapsed and/or refractory disease to at least 2 lines of therapy including either an anthracycline- or bendamustine- based regimen and a BTK inhibitor
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2
• Absolute neutrophil count (ANC) \>= 1,000/mm\^3
• Platelets \>= 50,000/mm\^3
• Total bilirubin \< 1.5 x institutional upper limit of normal (ULN). In patients with documented Gilbert's syndrome, total bilirubin =\< 2.5 x ULN
• Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) =\< 3 x ULN
• Creatinine clearance \>= 30 mL/min
• Patients must be willing to give written consent before performance of any study related procedures not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care
• Female patients who:
• Are postmenopausal for at least 1 year before the screening visit, OR
• Are surgically sterile, OR

You may not qualify if:

• Female patients who are lactating or have a positive serum pregnancy test during the screening period
• Failure to have fully recovered (i.e., =\< grade 1 toxicity) from the reversible effects of prior chemotherapy
• Major surgery within 14 days before enrollment
• 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
• Central nervous system involvement
• Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment. Patient may be eligible, if infectious disease specialist approves start of therapy AND subject has completed course of antibiotic therapy
• 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
• 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
• Ongoing or active systemic infection, active (deoxyribonucleic acid \[DNA\] polymerase chain reaction \[PCR\] positivity) hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
• Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
• Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing
• 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
• Patient has \>= grade 3 peripheral neuropathy, or grade 2 with pain on clinical examination during the screening period
• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

ixazomib; MLN2238; Rituximab; CT-P10

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Hun J Lee, MD
• Organization: MD Anderson Cancer Center

hunlee@mdanderson.org

713-792-2860

Study Officials

• Hun J Lee

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2019
• First Posted: August 7, 2019
• Study Start: August 28, 2019
• Primary Completion: June 1, 2024
• Study Completion: April 11, 2025
• Last Updated: April 20, 2025
• Results First Posted: December 16, 2024

Record last verified: 2025-04

Locations

US (1)