Study Stopped
Slow patient enrollment and study discontinued after 14 patients enrolled
Alisertib With and Without Rituximab in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
A Phase II Study of MLN8237 Alone and in Combination With Rituximab in Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphomas
2 other identifiers
interventional
14
1 country
2
Brief Summary
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started May 2013
Typical duration for phase_2
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 13, 2013
CompletedFirst Posted
Study publicly available on registry
March 15, 2013
CompletedStudy Start
First participant enrolled
May 21, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 14, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
April 20, 2017
CompletedResults Posted
Study results publicly available
June 6, 2018
CompletedJune 6, 2018
May 1, 2018
2.4 years
March 13, 2013
March 21, 2017
May 3, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
Up to 18 weeks (6 courses)
Secondary Outcomes (8)
Overall Response Rate (ORR)
6 weeks (2 courses)
Overall Response Rate (ORR)
12 weeks (4 courses)
Overall Response Rate(ORR)
18 weeks (6 courses)
Complete Response Rate (CR)
6 weeks (2 courses)
Complete Response Rate
12 weeks (4 courses)
- +3 more secondary outcomes
Study Arms (2)
Cohort A (alisertib, rituximab)
EXPERIMENTALPatients 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.
Cohort B (alisertib, rituximab)
EXPERIMENTALPatients 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.
Interventions
Given PO
Given IV
Laboratory correlative studies will be performed
Eligibility Criteria
You may qualify if:
- Must have histologically proven relapsed or refractory B-cell NHL of the following World Health Organization (WHO) classification subtypes: follicular lymphoma (FL), mantle cell lymphoma (MCL), lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia (LPL/WM), marginal zone lymphoma (MZL), diffuse large B-cell lymphoma (DLBCL), Burkitt's lymphoma (BL), and B-cell lymphoma with features unclassifiable between Burkitt's and large cell lymphoma; alternatively, patients with histologically proven, newly diagnosed transformed non-Hodgkin's lymphoma (tNHL) are eligible
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- At least one prior therapy; patients with newly diagnosed tNHL are eligible and do not need to have received prior therapy for the transformed lymphoma or prior indolent NHL; prior autologous stem cell transplant is allowed
- Serum creatinine =\< 2.0 mg/dL
- Total bilirubin within normal limits
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 1.5 x upper limit of normal
- Absolute neutrophil count (ANC) \>= 1000/μL
- Platelet count \>= 75,000/μL
- Recovery to =\< grade 1 toxicities associated with prior therapy
- Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
- Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study
- Male subject agrees to use an acceptable method for contraception during the entire study treatment period through 4 months after the last dose of MLN8237
- Must be able to take oral medication and to maintain a fast as required for 2 hours before and 1 hour after MLN8237 administration
You may not qualify if:
- Pregnant or breast-feeding women and women of childbearing age who are unwilling to use adequate contraception
- Patients with a history of central nervous system involvement by lymphoma
- Patients with known human immunodeficiency virus (HIV), hepatitis B or hepatitis C (active or carriers) are not eligible; this includes all patients with a positive hepatitis C antibody, hepatitis B surface antigen, or hepatitis B core antibody; previously vaccinated patients with positive hepatitis B surface antibody are eligible
- May not have received prior therapy with an Aurora kinase inhibitor
- Patients eligible for and willing to undergo autologous stem cell transplant with curative intent at the time of enrollment are not eligible; patients refractory to at least 2 prior regimens may enroll and proceed to curative autologous transplant if they respond
- Patients who are on chronic steroids for unrelated conditions (i.e. rheumatologic conditions) are not eligible if their total daily dose of steroids is equivalent to greater than 10 mg prednisone
- Radiation therapy to more than 25% of the bone marrow; whole pelvic radiation is considered to be over 25%
- Prior allogeneic bone marrow or organ transplantation
- If applicable, patient has \>= grade 2 peripheral neuropathy within 14 days before enrollment
- Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen
- Patients who are on daily proton pump inhibitor therapy must be able to discontinue use or only require use of antacid or hydrogen (H2) antagonist intermittently; patients who require daily administration of proton pump inhibitor, H2 antagonist, or pancreatic enzymes are not eligible; intermittent uses of antacids or H2 antagonists are allowed
- Systemic infection requiring IV antibiotic therapy within 14 days preceding the first dose of study drug, or other severe infection
- Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities (except asymptomatic patients with a pacemaker with electrocardiogram (ECG) changes reflecting conduction abnormalities secondary to the pacemaker); prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant
- Female subject is pregnant or breast-feeding; confirmation that the subject is not pregnant must be established by a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for post-menopausal or surgically sterilized women
- Patient has received other investigational drugs with 14 days before enrollment
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Emory University
Atlanta, Georgia, 30322, United States
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, 43210, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Study had slow patient enrollment and was discontinued after only 14 patients were enrolled.
Results Point of Contact
- Title
- Kristie Blum, MD
- Organization
- The Ohio State University James Comprehensive Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Kristie Blum, MD
Ohio State University Comprehensive Cancer Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 13, 2013
First Posted
March 15, 2013
Study Start
May 21, 2013
Primary Completion
October 14, 2015
Study Completion
April 20, 2017
Last Updated
June 6, 2018
Results First Posted
June 6, 2018
Record last verified: 2018-05