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TerminatedNCT01812005Updated Jun 6, 2018Results posted

Alisertib With and Without Rituximab in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

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

Why this study was terminated
Slow patient enrollment and study discontinued after 14 patients enrolled
Phase
Phase 2
Study type
Interventional
Enrollment
14
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study 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

Read the detailed description

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.

02

Conditions studied

  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • Nodal Marginal Zone B-cell Lymphoma
  • Recurrent Adult Burkitt Lymphoma
  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Recurrent Grade 1 Follicular Lymphoma
  • Recurrent Grade 2 Follicular Lymphoma
  • Recurrent Grade 3 Follicular Lymphoma
  • Recurrent Mantle Cell Lymphoma
  • Recurrent Marginal Zone Lymphoma
  • Splenic Marginal Zone Lymphoma
  • Waldenström Macroglobulinemia

Keywords

  • MLN8237
  • B-cell Non Hodgkin Lymphoma
  • Rituximab
03

In context

Burkitt Lymphoma

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 →

Lead sponsor

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.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 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

Exclusion criteria

Exclusion Criteria:

  • 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
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study
  • Other severe acute or chronic medical or psychiatric condition, including uncontrolled diabetes, malabsorption, resection of the pancreas or upper small bowel, requirement for pancreatic enzymes, any condition that would modify small bowel absorption of oral medications, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study
  • Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy
  • Treatment with clinically significant enzyme inducers, such as the enzyme- inducing antiepileptic drugs phenytoin, carbamazepine or phenobarbital, or rifampin, rifabutin, rifapentine or St. John's wort within 14 days prior to the first dose of MLN8237 and during the study
  • Patients with a corrected QT interval (QTc) at baseline of > 450 milliseconds or other factors that increase the risk of QT prolongation or arrhythmic events (i.e., heart failure, hypokalemia with potassium \< 3.5 despite supplementation, family history of long QT syndrome) should be excluded
  • Patients who require use of a concomitant medication that can prolong the QT interval and who are unable to discontinue use of this medication during the study period are excluded
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
14 participants (actual)

Study arms

  • Experimental
    Cohort A (alisertib, rituximab)

    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

  • Experimental
    Cohort B (alisertib, rituximab)

    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

Interventions

  • Drugalisertib

    Given PO

    Also known as: Aurora A kinase inhibitor MLN8237, MLN8237

  • Biologicalrituximab

    Given IV

    Also known as: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan

  • Otherlaboratory biomarker analysis

    Laboratory correlative studies will be performed

06

What researchers measure

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.

    Time frame: Up to 18 weeks (6 courses)

Secondary outcomes

  1. 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)

  2. Overall Response Rate (ORR)

    95% binomial confidence intervals calculated.

    Time frame: 12 weeks (4 courses)

  3. 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)

  4. 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)

  5. 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)

  6. 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

  7. 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

  8. 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)

07

Results

Posted Jun 6, 2018
Limitations and caveats
Study had slow patient enrollment and was discontinued after only 14 patients were enrolled.

Participant flow

Participant flow — Overall Study
MilestoneCohort A (Alisertib, Rituximab)Cohort B (Alisertib, Rituximab)
Started113
Completed113
Not completed00

Outcome measures

PrimaryBest 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)
Reported as:
Number · percentage of patients
Best Overall Response Rate (ORR) to Alisertib Alone
percentage of patientsCohort A (Alisertib, Rituximab)Cohort B (Alisertib, Rituximab)
Best Overall Response Rate (ORR) to Alisertib Alone0 (NA to NA)15 (2 to 45)
SecondaryOverall 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)
Reported as:
Number · percentage of patients
Overall Response Rate (ORR)
percentage of patientsCohort A (Alisertib, Rituximab)Cohort B (Alisertib, Rituximab)
Overall Response Rate (ORR)—8 (0 to 36)
SecondaryOverall Response Rate (ORR)

95% binomial confidence intervals calculated.

Time frame:
12 weeks (4 courses)

No measurements were reported for this outcome.

SecondaryOverall 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)
Reported as:
Number · percentage of patients
Overall Response Rate(ORR)
percentage of patientsCohort A (Alisertib, Rituximab)Cohort B (Alisertib, Rituximab)
Overall Response Rate(ORR)015
SecondaryComplete 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)
Reported as:
Number · percentage of patients
Complete Response Rate (CR)
percentage of patientsCohort A (Alisertib, Rituximab)Cohort B (Alisertib, Rituximab)
Complete Response Rate (CR)—0 (0 to 0)
SecondaryComplete 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)
Reported as:
Number · percentage of patients
Complete Response Rate
percentage of patientsCohort A (Alisertib, Rituximab)Cohort B (Alisertib, Rituximab)
Complete Response RateNA (NA to NA)—
SecondaryOverall 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
Reported as:
Median · months
Overall Survival
monthsCohort A (Alisertib, Rituximab)Cohort B (Alisertib, Rituximab)
Overall Survival—3.1 (1.7 to 27.6)
SecondaryProgression-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
Reported as:
Median · months
Progression-free Survival
monthsCohort A (Alisertib, Rituximab)Cohort B (Alisertib, Rituximab)
Progression-free Survival2 (NA to NA)1.2 (.8 to 2.5)
SecondaryComplete 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)

No measurements were reported for this outcome.

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Cohort A0/1 (0%)0/1 (0%)1/1 (100%)
Cohort B10/13 (76.9%)5/13 (38.5%)10/13 (76.9%)
Most frequent serious events
Showing 10 of 13
Most frequent serious events
EventCohort ACohort B
DehydrationMetabolism and nutrition disorders0/12/13
HypoxiaRespiratory, thoracic and mediastinal disorders0/11/13
PneumonitisRespiratory, thoracic and mediastinal disorders0/11/13
Duodenal obstructionGastrointestinal disorders0/11/13
AnemiaBlood and lymphatic system disorders0/11/13
FatigueGeneral disorders0/11/13
Generalized muscle weaknessMusculoskeletal and connective tissue disorders0/11/13
Abdominal painGastrointestinal disorders0/11/13
DyspneaRespiratory, thoracic and mediastinal disorders0/11/13
Thromboembolic eventVascular disorders0/11/13
Most frequent other events
Most frequent other events
EventCohort ACohort B
NeutropeniaBlood and lymphatic system disorders1/14/13
Febrile NeutropeniaInfections and infestations1/10/13
LymphopeniaBlood and lymphatic system disorders0/14/13
ThrombocytopeniaBlood and lymphatic system disorders0/11/13
FatigueGeneral disorders0/11/13

Baseline characteristics

Age, Continuous
Age, Continuous(years)Cohort A (Alisertib, Rituximab)Cohort B (Alisertib, Rituximab)Total
Median77 (77 to 77)58 (35 to 73)67.5 (35 to 77)
Sex: Female, Male
Sex: Female, Male(Participants)Cohort A (Alisertib, Rituximab)Cohort B (Alisertib, Rituximab)Total
Female033
Male11011
Region of Enrollment
Region of Enrollment(patients)Cohort A (Alisertib, Rituximab)Cohort B (Alisertib, Rituximab)Total
United States11314
08

Study locations

2 sites
  • 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
09

References and documents

Related links

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 6, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01812005
Lead sponsor
Ohio State University Comprehensive Cancer Center
Collaborators
Millennium Pharmaceuticals, Inc.
Responsible party
Sponsor
First posted
Mar 15, 2013
Start date
May 21, 2013
Primary completion
Oct 14, 2015
Completion
Apr 20, 2017
Results posted
Jun 6, 2018
Last update
Jun 6, 2018

Study contacts

Kristie Blum, MD
principal investigator · Ohio State University Comprehensive Cancer Center

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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