Recurrent Mantle Cell Lymphoma, Refractory Mantle Cell Lymphoma
Conditions
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.
Detailed description
PRIMARY OBJECTIVES: I. 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: I. 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: I. 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.
Interventions
DRUGIxazomib
Given by mouth
DRUGIxazomib Citrate
Given by mouth
BIOLOGICALRituximab
Given Intravenous
Sponsors
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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 * 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
Exclusion criteria
* 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 * Patients that have previously been treated with proteasome inhibitors, or participated in a study with proteasome inhibitors whether treated with proteasome inhibitors or not
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Remission Rate at 16 Weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate at 16 Weeks | 16 weeks | Evaluate the overall response rate (ORR) assessed by Lugano criteria (2014) |
| Progression Free Survival (PFS) and Overall Survival (OS) | 16 weeks | Evaluate progression free survival and overall survival |
| 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. | 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. |
Countries
United States
Participant flow
Recruitment details
Open label, single center, single-arm, phase II
Participants by arm
| Arm | Count |
|---|---|
| Study Drug Ixazomib 4mg PO on days 1, 8, 15 Rituximab 375 mg/m2 IV weekly until cycle 3, then given day 1 of each cycle | 3 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Progressive Disease | 1 |
Baseline characteristics
| Characteristic | Study Drug |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 3 |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 1 / 3 |
Outcome results
Primary
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.
Time frame: 16 weeks
Population: All endpoints will be measured on patients that received at least one dose of the study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Study Drug | Complete Remission Rate at 16 Weeks | 3 Participants |
Secondary
Overall Response Rate at 16 Weeks
Evaluate the overall response rate (ORR) assessed by Lugano criteria (2014)
Time frame: 16 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Study Drug | Overall Response Rate at 16 Weeks | 3 Participants |
Secondary
Progression Free Survival (PFS) and Overall Survival (OS)
Evaluate progression free survival and overall survival
Time frame: 16 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Study Drug | Progression Free Survival (PFS) and Overall Survival (OS) | Overall survival (OS) | 3 Participants |
| Study Drug | Progression Free Survival (PFS) and Overall Survival (OS) | Complete Metabolic Response (CMR) | 2 Participants |
Secondary
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.
Time frame: time of first dose of ixazomib through 30 days after the last dose of ixazomib was administered, up to 140 weeks.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Study Drug | Tolerability of Study Drug at Weeks 8, 16, 28, 42, and 56 | Week 8 | 0 Participants |
| Study Drug | Tolerability of Study Drug at Weeks 8, 16, 28, 42, and 56 | Week 16 | 0 Participants |
| Study Drug | Tolerability of Study Drug at Weeks 8, 16, 28, 42, and 56 | Week 28 | 0 Participants |
| Study Drug | Tolerability of Study Drug at Weeks 8, 16, 28, 42, and 56 | Week 42 | 0 Participants |
| Study Drug | Tolerability of Study Drug at Weeks 8, 16, 28, 42, and 56 | Week 56 | 0 Participants |