Diffuse Large B-cell LymphomaPhase 2NCT00807495
Study of Alisertib (MLN8237) in Adults With Aggressive Non-Hodgkin's Lymphoma
A Phase 2 study testing Alisertib in people with Diffuse Large B-cell Lymphoma and Mantle Cell Lymphoma, run by Millennium Pharmaceuticals, Inc. at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the anti-tumor activity of alisertib (MLN8237) in participants with relapsed or refractory non-hodgkin's lymphoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, Burkitt's Lymphoma
- What is being tested?
- Alisertib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Feb 2009to 13 Feb 2013
- 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
None listed.
Who cannot join
- Pregnant or lactating females.
- Known human immunodeficiency virus (HIV) positive or AIDS-related illness.
- Any serious medical or psychiatric illness that could interfere with the completion of treatment.
- Total bilirubin ≥ 1.5 × the upper limit of normal (ULN).
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≥ 2.5 × the ULN. AST, ALT may be elevated up to 5 times the ULN if their elevation can be reasonably ascribed to their underlying hematological disorder.
- Absolute neutrophil count (ANC) < 1,250/mm^3.
Show all 20Show fewer
- Platelet count < 75,000/mm^3.
- Calculated creatinine clearance < 30 mL/minute.
- Autologous stem cell transplant less than 6 months prior to enrollment.
- Participants who have undergone allogeneic stem cell or organ transplantation.
- Systemic antineoplastic therapy including glucocorticoids (> 15 mg prednisone/day or equivalent), or treatment with an investigational agent within 14 days preceding the first dose of study drug treatment.
- Participants who have received treatment with nitrosoureas, mitomycin C, rituximab, alemtuzumab, or other unconjugated antibody treatment, within 12 weeks prior to first dose.
- Participants who have received treatment with radioimmunoconjugates or within 12 weeks prior to first dose.
- Participants who have received radiotherapy within 21 days prior to first dose.
- Myocardial infarction within 6 months of enrollment or current history of New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia.
- Major surgery within 14 days prior to the first dose.
- Infection requiring systemic antibiotic therapy within 14 days prior to the first dose or other serious infection.
- Clinically uncontrolled central nervous system (CNS) involvement.
- Inability to swallow capsules.
- History of uncontrolled sleep apnoea syndrome and other conditions that could result in excessive daytime sleepiness (eg, Chronic obstructive pulmonary disease - COPD).
Trial locations and contacts
1 site in 1 country.
United States1 site
Hematology Oncology Associates, Virtua Memorial Hospital Burlington County
Mount Holly, New Jersey, 08060
About this study
Official title: A Phase 2 Trial of MLN8237, an Oral Aurora A Kinase Inhibitor, in Adult Patients With Aggressive Non-Hodgkin's Lymphoma
The purpose of this study is to evaluate the anti-tumor activity of alisertib (MLN8237) in participants with relapsed or refractory non-hodgkin's lymphoma.
Read the detailed description
The drug being tested in this study is called alisertib (MLN8237). Alisertib is being tested to treat people who have relapsed or refractory non-Hodgkin's lymphoma (NHL). The study looked at anti-tumor activity in participants who received alisertib.
The study enrolled 48 patients. Participants were categorized as per disease subtypes into five subtypes: Large B-Cell lymphoma, mantle cell lymphoma, transformed follicular lymphoma, Burkitts lymphoma and aggressive T-Cell lymphoma (Note: There were no participants enrolled with Precursor B-lymphoblastic Leukemia/Lymphoma). Participants received:
- Alisertib 50 mg BID on Days 1 to 7
All participants took alisertib capsules approximately every 12 hours each day for 7 days followed by a 14-day rest period in a 21-days cycle. MLN8237 was supplied in capsules of 5 or 25 mg strength.
This multi-center trial was conducted in United States. The overall time to participate in this study was until there is evidence of disease progression or unacceptable treatment-related toxicity. If the participant would derive benefit from continued alisertib treatment beyond 24 months, the Sponsor was consulted for approval of further treatment. Participants made multiple visits to the clinic, with imaging assessments every 12 weeks. Participants discontinuing treatment prior to disease progression continue with clinic visits, chemistry and hematology lab testing, and tumor assessments every 12 weeks up to 12 months after last dose of study drug for follow-up assessments.
- Conditions
- Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, Burkitt's Lymphoma, T-cell Lymphoma, Excluding Primary Cutaneous T-cell Lymphoma, Transformed Follicular Lymphoma With ≥ 50% Diffuse Large Cell Component
- Being tested
- Alisertib
- Keywords
- MLN8237, Alisertib, Drug therapy
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Lymphoma, Mantle-Cell, Burkitt Lymphoma, Lymphoma, T-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlisertibDrug
Also called MLN8237
Alisertib capsules
| Study group | Role | What they receive |
|---|---|---|
| Alisertib 50 mg | Experimental | Alisertib 50 mg, capsules, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 24 months or longer with Sponsor approval). Receives: Drug: Alisertib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best Overall Response Rate Based on Investigator's Assessment (Applying the IWG 2007 Response Criteria)
Best overall response rate is defined as the percentage of participants with complete response (CR) or partial response (PR) as assessed by the Investigator using International Working Group (IWG) Criteria. CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites (as specified in the Cheson 2007, IWG response criteria).
Measured: Baseline and every 2 cycles up to Month 12 (approximately 16 cycles), from Cycle 16 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months from last dose (Up to 4 years)
Secondary outcomes (6)
Time to Progression (TTP)
Time to progression (TTP) is defined as the time in days from the date of first study drug administration to the date of first documentation of Progressive Disease (PD) according to IWG criteria (Cheson 2007). PD is defined as any new lesion or increase by >50% of previously involved sites from nadir.
Measured: Baseline and every 2 cycles up to Month 12, from Cycle 16 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months (Up to 4 years)
Progression Free Survival (PFS)
PFS is defined as the time in days from the date of first study drug administration to the date of first documentation of progressive disease (PD) or death.
Measured: Baseline and every 2 cycles up to Month 12, from Cycle 16 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months (Up to 4 years)
Duration of Response (DOR)
DOR is defined as the time from the date of first documentation of a CR, or partial response (PR) to the date of first documentation of PD according to IWG criteria. CR definition includes the complete disappearance of all evidence of disease, the definition of PR includes at least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses, and PD is defined as any new lesion or increase by >50% of previously involved sites from nadir, as described in the IWG response criteria (Cheson 2007).
Measured: Baseline and every 2 cycles up to Month 12, from Cycle 16 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months (Up to 4 years)
Number of Participants With Treatment-Emergent Adverse Events
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug and includes all-causality (ie, treatment-related and not treatment-related as assessed by the investigator).
Measured: First dose of study drug to 30 days after last dose (Up to 25 months)
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events
Vital signs (blood pressure, heart rate, and oral temperature) measurements were obtained throughout the study. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Measured: First dose of study drug to 30 days after last dose (Up to 25 months)
Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events
Abnormal laboratory values for chemistry or hematology tests that were assessed by the investigator using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE V4). A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Measured: First dose of study drug to 30 days after last dose (Up to 25 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2008 (estimated)
- Study start10 Feb 2009
- Primary completion4 Jan 2011
- Study completion13 Feb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diffuse Large B-cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Millennium Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director Clinical Science, Study director, Millennium Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00807495
- Sponsor's protocol ID
- C14004
- Other IDs
- U1111-1187-1268
- Status last verified
- Feb 2018
- First submitted
- 11 Dec 2008
- Last updated
- 27 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V; International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007 Feb 10;25(5):579-86. doi: 10.1200/JCO.2006.09.2403. Epub 2007 Jan 22.
PubMed 17242396
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Trial of MLN8237, an Oral Aurora A Kinase Inhibitor, in Adult Patients With Aggressive Non-Hodgkin's Lymphoma
- ClinicalTrials.gov ID
- NCT00807495
- Acronym / sponsor ID
- C14004
- Conditions
- Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, Burkitt's Lymphoma, T-cell Lymphoma, Excluding Primary Cutaneous T-cell Lymphoma, Transformed Follicular Lymphoma With ≥ 50% Diffuse Large Cell Component
- Keywords
- MLN8237, Alisertib, Drug therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Millennium Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 10 Feb 2009 (actual)
- Primary completion
- 4 Jan 2011 (actual)
- Study completion
- 13 Feb 2013 (actual)
- First posted
- 12 Dec 2008 (estimated)
- Results
- Posted 27 Mar 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the anti-tumor activity of alisertib (MLN8237) in participants with relapsed or refractory non-hodgkin's lymphoma.
Detailed description
The drug being tested in this study is called alisertib (MLN8237). Alisertib is being tested to treat people who have relapsed or refractory non-Hodgkin's lymphoma (NHL). The study looked at anti-tumor activity in participants who received alisertib.
The study enrolled 48 patients. Participants were categorized as per disease subtypes into five subtypes: Large B-Cell lymphoma, mantle cell lymphoma, transformed follicular lymphoma, Burkitts lymphoma and aggressive T-Cell lymphoma (Note: There were no participants enrolled with Precursor B-lymphoblastic Leukemia/Lymphoma). Participants received:
- Alisertib 50 mg BID on Days 1 to 7
All participants took alisertib capsules approximately every 12 hours each day for 7 days followed by a 14-day rest period in a 21-days cycle. MLN8237 was supplied in capsules of 5 or 25 mg strength.
This multi-center trial was conducted in United States. The overall time to participate in this study was until there is evidence of disease progression or unacceptable treatment-related toxicity. If the participant would derive benefit from continued alisertib treatment beyond 24 months, the Sponsor was consulted for approval of further treatment. Participants made multiple visits to the clinic, with imaging assessments every 12 weeks. Participants discontinuing treatment prior to disease progression continue with clinic visits, chemistry and hematology lab testing, and tumor assessments every 12 weeks up to 12 months after last dose of study drug for follow-up assessments.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Alisertib 50 mg | Experimental | Drug: AlisertibAlisertib 50 mg, capsules, orally, twice daily for 7 days, followed by 14-day washout period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 24 months or longer with Sponsor approval). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (20 listed)
- Pregnant or lactating females.
- Known human immunodeficiency virus (HIV) positive or AIDS-related illness.
- Any serious medical or psychiatric illness that could interfere with the completion of treatment.
- Total bilirubin ≥ 1.5 × the upper limit of normal (ULN).
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≥ 2.5 × the ULN. AST, ALT may be elevated up to 5 times the ULN if their elevation can be reasonably ascribed to their underlying hematological disorder.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlisertibAlso: MLN8237Alisertib capsules | Drug | Alisertib 50 mg |
Primary outcome
Best Overall Response Rate Based on Investigator's Assessment (Applying the IWG 2007 Response Criteria)
Time frame: Baseline and every 2 cycles up to Month 12 (approximately 16 cycles), from Cycle 16 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months from last dose (Up to 4 years)
Best overall response rate is defined as the percentage of participants with complete response (CR) or partial response (PR) as assessed by the Investigator using International Working Group (IWG) Criteria. CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites (as specified in the Cheson 2007, IWG response criteria).
6 secondary outcomes
Time to Progression (TTP)
Time frame: Baseline and every 2 cycles up to Month 12, from Cycle 16 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months (Up to 4 years)
Progression Free Survival (PFS)
Time frame: Baseline and every 2 cycles up to Month 12, from Cycle 16 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months (Up to 4 years)
Duration of Response (DOR)
Time frame: Baseline and every 2 cycles up to Month 12, from Cycle 16 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months (Up to 4 years)
Number of Participants With Treatment-Emergent Adverse Events
Time frame: First dose of study drug to 30 days after last dose (Up to 25 months)
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events
Time frame: First dose of study drug to 30 days after last dose (Up to 25 months)
Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events
Time frame: First dose of study drug to 30 days after last dose (Up to 25 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 17242396Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V; International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007 Feb 10;25(5):579-86. doi: 10.1200/JCO.2006.09.2403. Epub 2007 Jan 22.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director Clinical Science study director
Millennium Pharmaceuticals, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Alisertib in people with Diffuse Large B-cell Lymphoma and Mantle Cell Lymphoma, run by Millennium Pharmaceuticals, Inc. at 1 site 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 0 inclusion and 20 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: finished, as of the sponsor's last update on 27 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 27 Mar 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 Based on Investigator's Assessment (Applying the IWG 2007 Response Criteria) (time frame: Baseline and every 2 cycles up to Month 12 (approximately 16 cycles), from Cycle 16 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months from last dose (Up to 4 years)). 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 NCT00807495, which also lists 1 linked publication.
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 27 Mar 2018.