A Phase 2 interventional study of alisertib and rituximab in Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Nodal Marginal Zone B-cell Lymphoma and Recurrent Adult Burkitt Lymphoma, sponsored by Ohio State University Comprehensive Cancer Center. Terminated at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-06-06.
Sponsored by Ohio State University Comprehensive Cancer Center · Phase 2, Interventional, and Treatment
This phase II trial studies how well alisertib with and without rituximab works in treating patients with relapsed or refractory B-cell non-Hodgkin lymphoma. Alisertib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving alisertib with and without rituximab may be an effective treatment for B-cell non-Hodgkin lymphoma
PRIMARY OBJECTIVES:
I. To determine the efficacy of MLN8237 (alisertib) alone in patients with relapsed and refractory non-Hodgkin lymphoma (NHL) and transformed NHL.
SECONDARY OBJECTIVES:
I. To determine the efficacy of MLN8237 when combined with rituximab in NHL patients who fail to respond to MLN8237 alone in patients with relapsed and refractory NHL and transformed NHL.
II. To determine specific toxicities associated with MLN8237 alone and when combined with rituximab (in NHL patients) in patients with relapsed and refractory NHL and transformed NHL.
III. To determine pharmacokinetics of MLN8237 alone and in combination with rituximab (for NHL patients) in patients with relapsed and refractory NHL and transformed NHL.
IV. To evaluate specific molecular characteristics of the NHL for patients treated with MLN8237 alone and with rituximab in order to correlate particular molecular markers with response and survival.
V. To evaluate long term survival of patients treated with MLN8237 alone and with rituximab.
OUTLINE: Patients are assigned to 1 of 2 treatment groups.
COHORT A: Patients receive alisertib orally (PO) twice daily (BID) on days 1-7. Patients unable to achieve complete response (CR) after course 4 also receive rituximab intravenously (IV) on day 1 of courses 5-12. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
COHORT B: Patients receive alisertib as in Cohort A. Patients achieving stable disease (SD) or asymptomatic progressive disease after 2 courses also receive rituximab IV on day 1 of courses 3-10. Patients unable to achieve CR by course 4, receive rituximab as in Cohort A. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for up to 2 years and then every 6 months.
392 studies on the registry are indexed under Burkitt Lymphoma; 114 are open to participants now.
This study's enrollment of 14 is below the median of 41 across 354 interventional studies indexed under Burkitt Lymphoma.
Browse Burkitt Lymphoma studies →Ohio State University Comprehensive Cancer Center is the lead sponsor of 369 studies on the registry; 81 are open to participants now.
Of its 38 completed or terminated interventional studies of FDA-regulated products, 19 (50%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Patients receive alisertib PO BID on days 1-7. Patients unable to achieve CR after course 4 also receive rituximab IV on day 1 of courses 5-12. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: alisertib · Biological: rituximab · Other: laboratory biomarker analysis
Patients receive alisertib as in Cohort A. Patients achieving SD or asymptomatic progressive disease after 2 courses also receive rituximab IV on day 1 of courses 3-10. Patients unable to achieve CR by course 4, receive rituximab as in Cohort A. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: alisertib · Biological: rituximab · Other: laboratory biomarker analysis
Given PO
Also known as: Aurora A kinase inhibitor MLN8237, MLN8237
Given IV
Also known as: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan
Laboratory correlative studies will be performed
Best Overall Response Rate (ORR) to Alisertib Alone
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: Up to 18 weeks (6 courses)
Overall Response Rate (ORR)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: 6 weeks (2 courses)
Overall Response Rate (ORR)
95% binomial confidence intervals calculated.
Time frame: 12 weeks (4 courses)
Overall Response Rate(ORR)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: 18 weeks (6 courses)
Complete Response Rate (CR)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: 6 weeks (2 courses)
Complete Response Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: 12 weeks (4 courses)
Overall Survival
Graphically summarized using the methods of Kaplan and Meier.
Time frame: Time from study entry to the time of death due to any cause, assessed up to 1 year
Progression-free Survival
Graphically summarized using the methods of Kaplan and Meier.
Time frame: Time from study entry to the time of progression and/or death, assessed up to 1 year
Complete Response Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: 18 weeks (6 courses)
| Milestone | Cohort A (Alisertib, Rituximab) | Cohort B (Alisertib, Rituximab) |
|---|---|---|
| Started | 1 | 13 |
| Completed | 1 | 13 |
| Not completed | 0 | 0 |
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
| percentage of patients | Cohort A (Alisertib, Rituximab) | Cohort B (Alisertib, Rituximab) |
|---|---|---|
| Best Overall Response Rate (ORR) to Alisertib Alone | 0 (NA to NA) | 15 (2 to 45) |
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
| percentage of patients | Cohort A (Alisertib, Rituximab) | Cohort B (Alisertib, Rituximab) |
|---|---|---|
| Overall Response Rate (ORR) | — | 8 (0 to 36) |
95% binomial confidence intervals calculated.
No measurements were reported for this outcome.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
| percentage of patients | Cohort A (Alisertib, Rituximab) | Cohort B (Alisertib, Rituximab) |
|---|---|---|
| Overall Response Rate(ORR) | 0 | 15 |
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
| percentage of patients | Cohort A (Alisertib, Rituximab) | Cohort B (Alisertib, Rituximab) |
|---|---|---|
| Complete Response Rate (CR) | — | 0 (0 to 0) |
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
| percentage of patients | Cohort A (Alisertib, Rituximab) | Cohort B (Alisertib, Rituximab) |
|---|---|---|
| Complete Response Rate | NA (NA to NA) | — |
Graphically summarized using the methods of Kaplan and Meier.
| months | Cohort A (Alisertib, Rituximab) | Cohort B (Alisertib, Rituximab) |
|---|---|---|
| Overall Survival | — | 3.1 (1.7 to 27.6) |
Graphically summarized using the methods of Kaplan and Meier.
| months | Cohort A (Alisertib, Rituximab) | Cohort B (Alisertib, Rituximab) |
|---|---|---|
| Progression-free Survival | 2 (NA to NA) | 1.2 (.8 to 2.5) |
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
No measurements were reported for this outcome.
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Cohort A | 0/1 (0%) | 0/1 (0%) | 1/1 (100%) |
| Cohort B | 10/13 (76.9%) | 5/13 (38.5%) | 10/13 (76.9%) |
| Event | Cohort A | Cohort B |
|---|---|---|
| DehydrationMetabolism and nutrition disorders | 0/1 | 2/13 |
| HypoxiaRespiratory, thoracic and mediastinal disorders | 0/1 | 1/13 |
| PneumonitisRespiratory, thoracic and mediastinal disorders | 0/1 | 1/13 |
| Duodenal obstructionGastrointestinal disorders | 0/1 | 1/13 |
| AnemiaBlood and lymphatic system disorders | 0/1 | 1/13 |
| FatigueGeneral disorders | 0/1 | 1/13 |
| Generalized muscle weaknessMusculoskeletal and connective tissue disorders | 0/1 | 1/13 |
| Abdominal painGastrointestinal disorders | 0/1 | 1/13 |
| DyspneaRespiratory, thoracic and mediastinal disorders | 0/1 | 1/13 |
| Thromboembolic eventVascular disorders | 0/1 | 1/13 |
| Event | Cohort A | Cohort B |
|---|---|---|
| NeutropeniaBlood and lymphatic system disorders | 1/1 | 4/13 |
| Febrile NeutropeniaInfections and infestations | 1/1 | 0/13 |
| LymphopeniaBlood and lymphatic system disorders | 0/1 | 4/13 |
| ThrombocytopeniaBlood and lymphatic system disorders | 0/1 | 1/13 |
| FatigueGeneral disorders | 0/1 | 1/13 |
| Age, Continuous(years) | Cohort A (Alisertib, Rituximab) | Cohort B (Alisertib, Rituximab) | Total |
|---|---|---|---|
| Median | 77 (77 to 77) | 58 (35 to 73) | 67.5 (35 to 77) |
| Sex: Female, Male(Participants) | Cohort A (Alisertib, Rituximab) | Cohort B (Alisertib, Rituximab) | Total |
|---|---|---|---|
| Female | 0 | 3 | 3 |
| Male | 1 | 10 | 11 |
| Region of Enrollment(patients) | Cohort A (Alisertib, Rituximab) | Cohort B (Alisertib, Rituximab) | Total |
|---|---|---|---|
| United States | 1 | 13 | 14 |
This study is terminated, as verified in May 2018. You cannot join it, but the record below documents what was studied.
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Ohio State University Comprehensive Cancer Center