Recurrent Mantle Cell LymphomaPhase 2NCT04047797
Ixazomib and Rituximab in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma
A Phase 2 study testing Ixazomib, Ixazomib Citrate and Rituximab in people with Recurrent Mantle Cell Lymphoma and Refractory Mantle Cell Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Mantle Cell Lymphoma, Refractory Mantle Cell Lymphoma
- What is being tested?
- Ixazomib, Ixazomib Citrate and Rituximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Aug 2019to 11 Apr 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug
- Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following:
- Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug
Who cannot join
- 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
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- 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
- Patients that have previously been treated with proteasome inhibitors, or participated in a study with proteasome inhibitors whether treated with proteasome inhibitors or not
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 2 Study of Ixazomib and Rituximab in Bruton Tyrosine Kinase Inhibitor Resistant Mantle Cell Lymphoma
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the complete remission rate of Bruton's tyrosine kinase (BTK) inhibitor refractory mantle cell lymphoma (MCL) patients with ixazomib citrate (ixazomib) and rituximab at 16 weeks of therapy.
SECONDARY OBJECTIVES:
- To evaluate overall response rate (ORR) assessed by Lugano criteria. II. To evaluate progression free survival (PFS) and overall survival (OS). III. To evaluate the safety and tolerability.
TERTIARY/EXPLORATORY OBJECTIVES:
- To evaluate biomarkers of response to treatment and mechanisms of resistance with pretreatment and post-treatment bone marrow and blood samples with deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) sequencing and immune profiling by flow cytometry.
OUTLINE:
Patients receive ixazomib orally (PO) 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 intravenously (IV) over 4-8 hours on days 1, 8, 15, and 22 of cycle 1. Beginning in cycle 3, patients receive rituximab IV 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.
After completion of study treatment, patients are followed up periodically.
- Being tested
- Ixazomib, Ixazomib Citrate, Rituximab
- Medical subject headings
- Lymphoma, Mantle-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IxazomibDrug
Also called MLN-2238, MLN2238
Given by mouth
Ixazomib CitrateDrug
Also called MLN-9708, MLN9708, Ninlaro
Given by mouth
RituximabBiological
Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody
Given Intravenous
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Ixazomib; Drug: Ixazomib Citrate; Biological: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 16 weeks
Secondary outcomes (3)
Overall Response Rate at 16 Weeks
Evaluate the overall response rate (ORR) assessed by Lugano criteria (2014)
Measured: 16 weeks
Progression Free Survival (PFS) and Overall Survival (OS)
Evaluate progression free survival and overall survival
Measured: 16 weeks
Tolerability of Study Drug at Weeks 8, 16, 28, 42, and 56
Tolerability of study drug at weeks 8, 16, 28, 42, and 56 using CTCAE v4.0 Toxicities or Adverse Events (grade 3 and up) were measured using CTCAE v 4.0 to determine the tolerability of ixazomib.
Measured: time of first dose of ixazomib through 30 days after the last dose of ixazomib was administered, up to 140 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2019
- Study start28 Aug 2019
- Primary completion1 Jun 2024
- Study completion11 Apr 2025
Why it stopped: Administratively Complete 75%\<Participants
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Recurrent Mantle Cell LymphomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Hun J Lee, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04047797
- Sponsor's protocol ID
- 2018-1090
- Other IDs
- NCI-2019-04857, 2018-1090
- Status last verified
- Apr 2025
- First submitted
- 5 Aug 2019
- Last updated
- 20 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Ixazomib and Rituximab in Bruton Tyrosine Kinase Inhibitor Resistant Mantle Cell Lymphoma
- ClinicalTrials.gov ID
- NCT04047797
- Acronym / sponsor ID
- 2018-1090
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Administratively Complete 75%\<Participants
- Enrolment
- 3 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 28 Aug 2019 (actual)
- Primary completion
- 1 Jun 2024 (actual)
- Study completion
- 11 Apr 2025 (actual)
- First posted
- 7 Aug 2019 (actual)
- Results
- Posted 16 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- To evaluate the complete remission rate of Bruton's tyrosine kinase (BTK) inhibitor refractory mantle cell lymphoma (MCL) patients with ixazomib citrate (ixazomib) and rituximab at 16 weeks of therapy.
SECONDARY OBJECTIVES:
- To evaluate overall response rate (ORR) assessed by Lugano criteria. II. To evaluate progression free survival (PFS) and overall survival (OS). III. To evaluate the safety and tolerability.
TERTIARY/EXPLORATORY OBJECTIVES:
- To evaluate biomarkers of response to treatment and mechanisms of resistance with pretreatment and post-treatment bone marrow and blood samples with deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) sequencing and immune profiling by flow cytometry.
OUTLINE:
Patients receive ixazomib orally (PO) 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 intravenously (IV) over 4-8 hours on days 1, 8, 15, and 22 of cycle 1. Beginning in cycle 3, patients receive rituximab IV 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.
After completion of study treatment, patients are followed up periodically.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (ixazomib, rituximab) | Experimental | Drug: Ixazomib, Drug: Ixazomib Citrate, Biological: RituximabPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patients must have histologically confirmed diagnosis of mantle cell lymphoma
- Patients must have measurable disease, as defined by at least one of the following:
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IxazomibAlso: MLN-2238, MLN2238Given by mouth | Drug | Treatment (ixazomib, rituximab) |
| Ixazomib CitrateAlso: MLN-9708, MLN9708, NinlaroGiven by mouth | Drug | Treatment (ixazomib, rituximab) |
| RituximabAlso: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 AntibodyGiven Intravenous | Biological | Treatment (ixazomib, rituximab) |
Primary outcome
Complete Remission Rate at 16 Weeks
Time frame: 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.
3 secondary outcomes
Overall Response Rate at 16 Weeks
Time frame: 16 weeks
Progression Free Survival (PFS) and Overall Survival (OS)
Time frame: 16 weeks
Tolerability of Study Drug at Weeks 8, 16, 28, 42, and 56
Time frame: time of first dose of ixazomib through 30 days after the last dose of ixazomib was administered, up to 140 weeks.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- MD Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hun J Lee principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ixazomib, Ixazomib Citrate and Rituximab in people with Recurrent Mantle Cell Lymphoma and Refractory Mantle Cell Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete Remission Rate at 16 Weeks (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2025.