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Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissuePhase 2NCT01812005

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

A Phase 2 study testing alisertib, rituximab and laboratory biomarker analysis in people with Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue and Nodal Marginal Zone B-cell Lymphoma, run by Ohio State University Comprehensive Cancer Center at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
alisertib, rituximab and laboratory biomarker analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
2 sitesUnited States
Study dates
21 May 2013to 20 Apr 2017
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

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Emory University

    Atlanta, Georgia, 30322

  • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: A Phase II Study of MLN8237 Alone and in Combination With Rituximab in Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphomas

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:

  1. To determine the efficacy of MLN8237 (alisertib) alone in patients with relapsed and refractory non-Hodgkin lymphoma (NHL) and transformed NHL.

SECONDARY OBJECTIVES:

  1. 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.

  1. 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.

Being tested
alisertib, rituximab, laboratory biomarker analysis
Keywords
MLN8237, B-cell Non Hodgkin Lymphoma, Rituximab
Medical subject headings
Lymphoma, B-Cell, Marginal Zone, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Lymphoma, Mantle-Cell, Waldenstrom Macroglobulinemia, Lymphoma, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • alisertibDrug

    Also called Aurora A kinase inhibitor MLN8237, MLN8237

    Given PO

  • rituximabBiological

    Also called IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8

    Given IV

  • laboratory biomarker analysisOther

    Laboratory correlative studies will be performed

Study groups in NCT01812005
Study groupRoleWhat they receive
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.
Receives: Drug: alisertib; Biological: rituximab; Other: laboratory biomarker analysis
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.
Receives: Drug: alisertib; Biological: rituximab; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 18 weeks (6 courses)

Secondary outcomes (8)

  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.

    Measured: 6 weeks (2 courses)

  2. Overall Response Rate (ORR)

    95% binomial confidence intervals calculated.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 12 weeks (4 courses)

  6. Overall Survival

    Graphically summarized using the methods of Kaplan and Meier.

    Measured: 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.

    Measured: 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.

    Measured: 18 weeks (6 courses)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Mar 2013 (estimated)
  2. Study start21 May 2013
  3. Primary completion14 Oct 2015
  4. Study completion20 Apr 2017

Why it stopped: Slow patient enrollment and study discontinued after 14 patients enrolled

Resources

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01812005
Sponsor's protocol ID
OSU-12106
Other IDs
NCI-2012-02794
Status last verified
May 2018
First submitted
13 Mar 2013
Last updated
6 Jun 2018
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing alisertib, rituximab and laboratory biomarker analysis in people with Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue and Nodal Marginal Zone B-cell Lymphoma, run by Ohio State University Comprehensive Cancer Center at 2 sites 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 13 inclusion and 21 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 6 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 6 Jun 2018). 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?

Best Overall Response Rate (ORR) to Alisertib Alone (time frame: Up to 18 weeks (6 courses)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01812005.

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 6 Jun 2018.

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