Diffuse Large B-Cell LymphomaPhase 1/2NCT01397825
MLN8237 in Patients With Relapsed or Refractory Aggressive B-Cell Lymphoma Treated With Rituximab +/- Vincristine
A Phase 1/2 study testing Alisertib (MLN8237), Rituximab and Vincristine in people with Diffuse Large B-Cell Lymphoma and Transformed Follicular Lymphoma, run by Millennium Pharmaceuticals, Inc. at 25 sites in 4 countries.
Trial summary
This is a single-arm, open-label, multicenter, dose escalation, phase 1-2 study of alisertib (MLN8237) administered in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL)/transformed follicular lymphoma (TFL) treated with rituximab and vincristine. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B-Cell Lymphoma, Transformed Follicular Lymphoma, Mantle Cell Lymphoma
- What is being tested?
- Alisertib (MLN8237), Rituximab and Vincristine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 25 sitesin 4 countries
- Study dates
- 9 Aug 2011to 5 Oct 2016
- Phase
- Phase 1/2
- 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
- Histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL)/transformed follicular lymphoma (TFL). Note: Patients with Mantle Cell or Burkitt's lymphoma may be eligible for enrollment to the safety lead-in and dose escalation cohorts, parts 1 \& 2 only
- Relapsed or refractory after at least 1 prior systemic treatment for aggressive lymphoma (including anthracycline unless contra-indicated). Relapse following an autologous stem cell transplant is allowed.
- Relapsed after autologous stem cell transplantation or not be eligible for autologous stem cell transplantation or refuse autologous stem cell transplantation. Patients enrolled to the phase 2 part must have received prior rituximab.
- Measurable disease as specified in study protocol
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- Female patients who are post menopausal for at least 1 year, surgically sterile, or agree to practice 2 effective methods of contraception through 30 days after the last dose of alisertib (MLN8237) or agree to abstain from heterosexual intercourse. Patients should also use effective contraception for 12 months following the last dose of rituximab and 1 month following the last dose of alisertib (MLN8237.
- Male patients who agree to practice effective barrier contraception through 4 months after the last dose of MLN8237 or agree to abstain from heterosexual intercourse
- Voluntary written consent
Who cannot join
- Received more than 4 prior systemic treatment regimens for lymphoma
- Known human immunodeficiency virus (HIV) positive or acquired immunodeficiency syndrome (AIDS)-related illness; hepatitis B virus, or hepatitis C virus; known history of Charcot-Marie-Tooth disease or polio
- Autologous stem cell transplant less than 3 months prior to enrollment
- Patients who have undergone allogeneic stem cell or organ transplantation any time
- Systemic antineoplastic therapy, including glucocorticoids or treatment with an investigational agent within 14 days preceding the first dose of study drug treatment. Steroids are permitted for administration with rituximab to prevent or treat infusion reaction
- Treatment with nitrosoureas, mitomycin C, rituximab, alemtuzumab, or other unconjugated antibody treatment within 42 days (21 days if clear evidence of progressive disease) prior to the first day of study drug treatment
Show all 21Show fewer
- Treatment with radioimmunoconjugates or toxin immunoconjugates, such as ibritumomab-tiuxetan, or tositumomab, within 12 weeks prior to the first day of study drug treatment
- Radiotherapy within 21 days prior to the first dose of study drug treatment
- Treatment with enzyme-inducing antiepileptic drugs, such as phenytoin, carbamazepine, or phenobarbital, or with rifampin, rifabutin, rifapentine, or St. John's wort, within 14 days prior to the first dose of alisertib (MLN8237) also not permitted during study
- Cardiac status as described in protocol
- Major surgery, serious infection, or infection requiring systemic antibiotic therapy within 14 days prior to the first dose of study treatment
- History of hemorrhagic or thrombotic cerebrovascular event in the past 12 months
- Clinically uncontrolled central nervous system involvement
- Inability to receive IV rituximab or vincristine, or to swallow tablets or inability or unwillingness to avoid taking anything by mouth except for water and prescribed medications for 2 hours before and 1 hour after each dose of alisertib (MLN8237)
- History of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness
- Female patients who are lactating or pregnant
- Serious medical or psychiatric illness or laboratory abnormality that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol
- Clinically apparent ≥ Grade 2 neuropathy due to any cause in the 3 months prior to enrollment, or history of ≥ Grade 3 neuropathy related to vincristine at any time
- Prior treatment with Aurora A-targeted agents, including alisertib (MLN8237)
- Patients who have received myeloid growth factors or platelet transfusion within 14 days prior to the first dose of study treatment
- Patients with known hypersensitivity to rituximab, vincristine (or vinca alkaloids), or their diluents
Trial locations and contacts
25 sites in 4 countries.
25 sites in 4 countries
United States15 sites
Study site
Beverly Hills, California
Study site
Burbank, California
Study site
Burlington, Vermont
Study site
Chapel Hill, North Carolina
Study site
Germantown, Tennessee
Study site
Houston, Texas
Study site
Lexington, Kentucky
Study site
Memphis, Tennessee
Study site
Miami, Florida
Study site
New York, New York
Study site
Philadelphia, Pennsylvania
Study site
Rochester, New York
Study site
San Antonio, Texas
Study site
Tucson, Arizona
Study site
Worcester, Massachusetts
Italy4 sites
Study site
Genova
Study site
Orbassano, Torino
Study site
Palermo
Study site
Roma
United Kingdom4 sites
Study site
Aberdeen, Grampian Region
Study site
Birmingham, West Midlands
Study site
London, Greater London
Study site
Southampton, Hampshire
About this study
Official title: A Multicenter, Phase 1-2 Study of MLN8237, an Oral Aurora A Kinase Inhibitor, in Patients With Relapsed or Refractory Aggressive B-Cell Lymphoma Treated With Rituximab and Vincristine
This is a single-arm, open-label, multicenter, dose escalation, phase 1-2 study of alisertib (MLN8237) administered in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL)/transformed follicular lymphoma (TFL) treated with rituximab and vincristine. The study has three parts as follows:
Phase 1, Part 1: Safety lead-in cohort to evaluate alisertib (MLN8237) and rituximab.
Read more
Phase 1, Part 2: Dose escalation cohort to evaluate alisertib (MLN8237) + Rituximab + Vincristine and determine Phase 2 dose. Patients with other types of B-cell lymphoma (including mantle cell or Burkitt's lymphoma may enroll in Parts 1 and 2.
Phase 2: Alisertib (MLN8237) + Rituximab + Vincristine in patients with relapsed or refractory DLBCL or TFL at recommended Phase 2 dose.
Note that in 2013 Sponsor decision was taken to not initiate the phase 2 portion of the trial, which would have investigated the triplet at the recommended phase 2 dose identified in part 2. This decision was based on reprioritization within the company and not on any clinical or safety outcomes observed.
Read the detailed description
The drug tested in this study was called alisertib. Alisertib was tested to treat people who have relapsed or refractory diffuse large B-cell lymphoma or other aggressive B-cell lymphomas. This study looked at safety, any anti-tumor effect, and it also determined a recommended dose of alisertib plus rituximab and alisertib plus rituximab and vincristine to take into further studies. Pharmacokinetic blood samples were studied to characterize any effects on the concentration of each of the drugs when administered together .
The study enrolled 45 patients. Participants received the following treatments:
Phase 1
- Alisertib 50 mg + rituximab in the Safety Lead-in
- Alisertib 30 mg + rituximab + vincristine in the Dose Escalation
- Alisertib 40 mg + rituximab + vincristine in the Dose Escalation
- Alisertib 50 mg + rituximab + vincristine in the Dose Escalation
All participants were asked to take one alisertib table twice a day for 7 days in each cycle for up to 8 cycles along with rituximab on Day 1 of each cycle; some patients also received vincristine on Day 1 and Day 8 of each cycle. All participants with documented disease response or stabilization could continue with alisertib single-agent therapy for an additional 2 years or more.
This multi-center trial was conducted in the USA. The overall time to participate in this study was up to 5.2 years. Participants made multiple visits to the clinic, plus a final visit 30 days after receiving their last dose of study drug for a follow-up assessment.
- Conditions
- Diffuse Large B-Cell Lymphoma, Transformed Follicular Lymphoma, Mantle Cell Lymphoma, Burkitt's Lymphoma
- Being tested
- Alisertib (MLN8237), Rituximab, Vincristine
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Lymphoma, Mantle-Cell, Burkitt Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alisertib (MLN8237)Drug
Alisertib (MLN8237) enteric coated tablet (ECT).
RituximabDrug
Rituximab IV infusion.
VincristineDrug
Vincristine IV Infusion.
| Study group | Role | What they receive |
|---|---|---|
| Safety Lead-in | Experimental | Alisertib 50 mg, enteric coated tablets (ECT), orally, twice daily (BID), on Days 1 to 7 followed by a 14-day rest period in 21-day cycles plus rituximab 375 mg/m^2, intravenous (IV), infusion on Day 1 of each 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years. Receives: Drug: Alisertib (MLN8237); Drug: Rituximab |
| Dose Escalation, Alisertib 30 mg | Experimental | Alisertib 30 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1, plus vincristine 1.4 mg/m^2 (max 2 mg), IV, on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/ or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years. Receives: Drug: Alisertib (MLN8237); Drug: Rituximab; Drug: Vincristine |
| Dose Escalation, Alisertib 40 mg | Experimental | Alisertib 40 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/ or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years. Receives: Drug: Alisertib (MLN8237); Drug: Rituximab; Drug: Vincristine |
| Dose Escalation, Alisertib 50 mg | Experimental | Alisertib 50 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/ or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years. Receives: Drug: Alisertib (MLN8237); Drug: Rituximab; Drug: Vincristine |
| Phase 2: Alisertib | Experimental | Phase 2: Alisertib (MLN8237) at the Recommended Phase 2 Dose, ECT orally twice/day on Days 1-7 \& rituximab as an IV infusion on Day 1 \& vincristine IV on Days 1 \& 8 in a 21 Day cycle for up to 8 cycles was planned but not conducted. Receives: Drug: Alisertib (MLN8237); Drug: Rituximab; Drug: Vincristine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Clinically Significant Vital Signs Findings (Treatment Related and Unrelated) [Phase 1]
Vital sign parameters: blood pressure, heart rate and temperature determined by the investigator to be clinically significant were reported as adverse events.
Measured: First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)
Number of Participants With Clinically Significant Changes in Electrocardiograms (ECGs) [Phase 1]
Abnormal ECGs findings determined by the investigator to be clinically significant were reported as adverse events.
Measured: First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)
Number of Participants With Clinically Significant Changes in Multigated Acquisition (MUGA)/ Echocardiogram (ECHO) [Phase 1]
Abnormal changes in MUGA and ECHO findings determined by the investigator to be clinically significant were reported as adverse events.
Measured: First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)
Number of Participants With Clinically Significant Changes in Physical Examination Findings [Phase 1]
Abnormal Physical Examination findings determined by the investigator to be clinically significant were reported as Adverse Events.
Measured: First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)
Number of Participants With Clinically Significant Laboratory Tests Reported as Adverse Events [Phase 1]
Abnormal treatment-emergent Chemistry and Hematology Laboratory values determined by the investigator to be clinically significant were reported as adverse events.
Measured: First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)
Number of Participants With Treatment-Emergent Adverse Events [Phase 1]
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.
Measured: First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)
Overall Response Rate [Phase 2]
Overall Response Rate was 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.
Measured: At the end of Cycle 2, at the end of every second treatment cycle until 6 months, then every 12 weeks thereafter, approximately 2 years
Secondary outcomes (16)
Overall Response Rate as Assessed by the Investigator [Phase 1]
Overall Response Rate was 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.
Measured: First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)
Complete Response Rate [Phase 2]
Complete response rate was defined as the percentage of participants with Complete Response (CR). CR was assessed by the investigator using International Working Group (IWG) Criteria. CR is defined as the disappearance of all evidence of disease.
Measured: Duration of study until disease progression, approximately 2 years
Duration of Response (DOR) [Phase 2]
DOR was defined as the time from the date of first documentation of a response to the date of first documentation of Progressive Disease (PD).
Measured: Duration of study until disease progression, approximately 2 years
Progression Free Survival (PFS) [Phase 2]
PFS was defined as the time from the date of first study drug administration to the date of first documentation of PD or death.
Measured: Duration of study until disease progression, approximately 2 years
Number of Participants With Treatment-Emergent Adverse Events [Phase 2]
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.
Measured: From screening period to 30 days after last dose of study drug, approximately 2 years
Number of Participants With Clinically Significant Vital Signs Findings [Phase 2]
Vital sign parameters: blood pressure, heart rate and temperature determined by the investigator to be clinically significant were reported as adverse events.
Measured: From screening period to 30 days after last dose of study drug, approximately 2 years
Number of Participants With Clinically Significant Changes in Electrocardiograms (ECGs) [Phase 2]
Measured: From screening period to 30 days after last dose of study drug, approximately 2 years
Number of Participants With Clinically Significant Changes in Multigated Acquisition (MUGA)/ Echocardiogram (ECHO) [Phase 2]
Measured: From screening period to 30 days after last dose of study drug, approximately 2 years
Number of Participants With Clinically Significant Laboratory Tests Reported as Adverse Events [Phase 2]
Measured: From screening period to 30 days after last dose of study drug, approximately 2 years
Cmax: Maximum Plasma Concentration for Alisertib
Measured: Cycle 1 Days 1 and 7 prior to morning alisertib dose and multiple time-points (up to 12 hours) post-dose
Tmax: Time to First Occurrence of Cmax fo Alisertib
Measured: Cycle 1 Days 1 and 7 prior to morning alisertib dose and multiple time-points (up to 12 hours) post-dose
AUCt: Area Under the Concentration Time Curve Over the Dosing Interval From Time 0 to Time t for Alisertib
Measured: Cycle 1 Days 1 and 7 prior to morning alisertib dose and multiple time-points (up to 12 hours) post-dose
Cmax: Maximum Plasma Concentration for Vincristine
Measured: Cycles 1 and 2 on Day 1 prior to injection of vincristine and multiple time-points (up to 72 hours) post-dose
AUCt: Area Under the Concentration-time Time Curve Over the Dosing Interval From Time 0 to Time t for Vincristine
Measured: Cycles 1 and 2 on Day 1 prior to injection of vincristine and multiple time-points (up to 72 hours) post-dose
AUC∞: Area Under the Concentration-time Curve From Time 0 to Infinity for Vincristine
Measured: Cycles 1 and 2 on Day 1 prior to injection of vincristine and multiple time-points (up to 72 hours) post-dose
T1/2: Terminal Disposition Phase Half-life for Vincristine
Measured: Cycles 1 and 2 on Day prior to injection of vincristine and multiple time-points (up to 72 hours) post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2011 (estimated)
- Study start9 Aug 2011
- Primary completion5 Feb 2015
- Study completion5 Oct 2016
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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Millennium Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Millennium Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01397825
- Sponsor's protocol ID
- C14011
- Other IDs
- 2011-000609-32, U1111-1181-0333, 12/NE/0268
- Status last verified
- Feb 2018
- First submitted
- 17 Jul 2011
- Last updated
- 27 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Kelly KR, Friedberg JW, Park SI, McDonagh K, Hayslip J, Persky D, Ruan J, Puvvada S, Rosen P, Iyer SP, Stefanovic A, Bernstein SH, Weitman S, Karnad A, Monohan G, VanderWalde A, Mena R, Schmelz M, Spier C, Groshen S, Venkatakrishnan K, Zhou X, Sheldon-Waniga E, Leonard EJ, Mahadevan D. Phase I Study of the Investigational Aurora A Kinase Inhibitor Alisertib plus Rituximab or Rituximab/Vincristine in Relapsed/Refractory Aggressive B-cell Lymphoma. Clin Cancer Res. 2018 Dec 15;24(24):6150-6159. doi: 10.1158/1078-0432.CCR-18-0286. Epub 2018 Aug 6.
PubMed 30082475
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 Multicenter, Phase 1-2 Study of MLN8237, an Oral Aurora A Kinase Inhibitor, in Patients With Relapsed or Refractory Aggressive B-Cell Lymphoma Treated With Rituximab and Vincristine
- ClinicalTrials.gov ID
- NCT01397825
- Acronym / sponsor ID
- C14011
- Conditions
- Diffuse Large B-Cell Lymphoma, Transformed Follicular Lymphoma, Mantle Cell Lymphoma, Burkitt's Lymphoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Millennium Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 9 Aug 2011 (actual)
- Primary completion
- 5 Feb 2015 (actual)
- Study completion
- 5 Oct 2016 (actual)
- First posted
- 20 Jul 2011 (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.
This is a single-arm, open-label, multicenter, dose escalation, phase 1-2 study of alisertib (MLN8237) administered in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL)/transformed follicular lymphoma (TFL) treated with rituximab and vincristine. The study has three parts as follows:
Phase 1, Part 1: Safety lead-in cohort to evaluate alisertib (MLN8237) and rituximab.
Phase 1, Part 2: Dose escalation cohort to evaluate alisertib (MLN8237) + Rituximab + Vincristine and determine Phase 2 dose. Patients with other types of B-cell lymphoma (including mantle cell or Burkitt's lymphoma may enroll in Parts 1 and 2.
Phase 2: Alisertib (MLN8237) + Rituximab + Vincristine in patients with relapsed or refractory DLBCL or TFL at recommended Phase 2 dose.
Note that in 2013 Sponsor decision was taken to not initiate the phase 2 portion of the trial, which would have investigated the triplet at the recommended phase 2 dose identified in part 2. This decision was based on reprioritization within the company and not on any clinical or safety outcomes observed.
Detailed description
The drug tested in this study was called alisertib. Alisertib was tested to treat people who have relapsed or refractory diffuse large B-cell lymphoma or other aggressive B-cell lymphomas. This study looked at safety, any anti-tumor effect, and it also determined a recommended dose of alisertib plus rituximab and alisertib plus rituximab and vincristine to take into further studies. Pharmacokinetic blood samples were studied to characterize any effects on the concentration of each of the drugs when administered together .
The study enrolled 45 patients. Participants received the following treatments:
Phase 1
- Alisertib 50 mg + rituximab in the Safety Lead-in
- Alisertib 30 mg + rituximab + vincristine in the Dose Escalation
- Alisertib 40 mg + rituximab + vincristine in the Dose Escalation
- Alisertib 50 mg + rituximab + vincristine in the Dose Escalation
All participants were asked to take one alisertib table twice a day for 7 days in each cycle for up to 8 cycles along with rituximab on Day 1 of each cycle; some patients also received vincristine on Day 1 and Day 8 of each cycle. All participants with documented disease response or stabilization could continue with alisertib single-agent therapy for an additional 2 years or more.
This multi-center trial was conducted in the USA. The overall time to participate in this study was up to 5.2 years. Participants made multiple visits to the clinic, plus a final visit 30 days after receiving their last dose of study drug for a follow-up assessment.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Safety Lead-in | Experimental | Drug: Alisertib (MLN8237), Drug: RituximabAlisertib 50 mg, enteric coated tablets (ECT), orally, twice daily (BID), on Days 1 to 7 followed by a 14-day rest period in 21-day cycles plus rituximab 375 mg/m^2, intravenous (IV), infusion on Day 1 of each 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years. |
| Dose Escalation, Alisertib 30 mg | Experimental | Drug: Alisertib (MLN8237), Drug: Rituximab, Drug: VincristineAlisertib 30 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1, plus vincristine 1.4 mg/m^2 (max 2 mg), IV, on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/ or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years. |
| Dose Escalation, Alisertib 40 mg | Experimental | Drug: Alisertib (MLN8237), Drug: Rituximab, Drug: VincristineAlisertib 40 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/ or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years. |
| Dose Escalation, Alisertib 50 mg | Experimental | Drug: Alisertib (MLN8237), Drug: Rituximab, Drug: VincristineAlisertib 50 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/ or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years. |
| Phase 2: Alisertib | Experimental | Drug: Alisertib (MLN8237), Drug: Rituximab, Drug: VincristinePhase 2: Alisertib (MLN8237) at the Recommended Phase 2 Dose, ECT orally twice/day on Days 1-7 \& rituximab as an IV infusion on Day 1 \& vincristine IV on Days 1 \& 8 in a 21 Day cycle for up to 8 cycles was planned but not conducted. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL)/transformed follicular lymphoma (TFL). Note: Patients with Mantle Cell or Burkitt's lymphoma may be eligible for enrollment to the safety lead-in and dose escalation cohorts, parts 1 \& 2 only
- Relapsed or refractory after at least 1 prior systemic treatment for aggressive lymphoma (including anthracycline unless contra-indicated). Relapse following an autologous stem cell transplant is allowed.
- Relapsed after autologous stem cell transplantation or not be eligible for autologous stem cell transplantation or refuse autologous stem cell transplantation. Patients enrolled to the phase 2 part must have received prior rituximab.
- Measurable disease as specified in study protocol
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
Key exclusion criteria (21 listed)
- Received more than 4 prior systemic treatment regimens for lymphoma
- Known human immunodeficiency virus (HIV) positive or acquired immunodeficiency syndrome (AIDS)-related illness; hepatitis B virus, or hepatitis C virus; known history of Charcot-Marie-Tooth disease or polio
- Autologous stem cell transplant less than 3 months prior to enrollment
- Patients who have undergone allogeneic stem cell or organ transplantation any time
- Systemic antineoplastic therapy, including glucocorticoids or treatment with an investigational agent within 14 days preceding the first dose of study drug treatment. Steroids are permitted for administration with rituximab to prevent or treat infusion reaction
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 |
|---|---|---|
| Alisertib (MLN8237)Alisertib (MLN8237) enteric coated tablet (ECT). | Drug | Dose Escalation, Alisertib 30 mg, Dose Escalation, Alisertib 40 mg, Dose Escalation, Alisertib 50 mg, Phase 2: Alisertib, Safety Lead-in |
| RituximabRituximab IV infusion. | Drug | Dose Escalation, Alisertib 30 mg, Dose Escalation, Alisertib 40 mg, Dose Escalation, Alisertib 50 mg, Phase 2: Alisertib, Safety Lead-in |
| VincristineVincristine IV Infusion. | Drug | Dose Escalation, Alisertib 30 mg, Dose Escalation, Alisertib 40 mg, Dose Escalation, Alisertib 50 mg, Phase 2: Alisertib |
Primary outcome
Number of Participants With Clinically Significant Vital Signs Findings (Treatment Related and Unrelated) [Phase 1]
Time frame: First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)
Vital sign parameters: blood pressure, heart rate and temperature determined by the investigator to be clinically significant were reported as adverse events.
Number of Participants With Clinically Significant Changes in Electrocardiograms (ECGs) [Phase 1]
Time frame: First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)
Abnormal ECGs findings determined by the investigator to be clinically significant were reported as adverse events.
Number of Participants With Clinically Significant Changes in Multigated Acquisition (MUGA)/ Echocardiogram (ECHO) [Phase 1]
Time frame: First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)
Abnormal changes in MUGA and ECHO findings determined by the investigator to be clinically significant were reported as adverse events.
Number of Participants With Clinically Significant Changes in Physical Examination Findings [Phase 1]
Time frame: First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)
Abnormal Physical Examination findings determined by the investigator to be clinically significant were reported as Adverse Events.
Number of Participants With Clinically Significant Laboratory Tests Reported as Adverse Events [Phase 1]
Time frame: First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)
Abnormal treatment-emergent Chemistry and Hematology Laboratory values determined by the investigator to be clinically significant were reported as adverse events.
Number of Participants With Treatment-Emergent Adverse Events [Phase 1]
Time frame: First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)
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.
Overall Response Rate [Phase 2]
Time frame: At the end of Cycle 2, at the end of every second treatment cycle until 6 months, then every 12 weeks thereafter, approximately 2 years
Overall Response Rate was 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.
16 secondary outcomes
Overall Response Rate as Assessed by the Investigator [Phase 1]
Time frame: First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)
Complete Response Rate [Phase 2]
Time frame: Duration of study until disease progression, approximately 2 years
Duration of Response (DOR) [Phase 2]
Time frame: Duration of study until disease progression, approximately 2 years
Progression Free Survival (PFS) [Phase 2]
Time frame: Duration of study until disease progression, approximately 2 years
Number of Participants With Treatment-Emergent Adverse Events [Phase 2]
Time frame: From screening period to 30 days after last dose of study drug, approximately 2 years
Number of Participants With Clinically Significant Vital Signs Findings [Phase 2]
Time frame: From screening period to 30 days after last dose of study drug, approximately 2 years
Number of Participants With Clinically Significant Changes in Electrocardiograms (ECGs) [Phase 2]
Time frame: From screening period to 30 days after last dose of study drug, approximately 2 years
Number of Participants With Clinically Significant Changes in Multigated Acquisition (MUGA)/ Echocardiogram (ECHO) [Phase 2]
Time frame: From screening period to 30 days after last dose of study drug, approximately 2 years
Number of Participants With Clinically Significant Laboratory Tests Reported as Adverse Events [Phase 2]
Time frame: From screening period to 30 days after last dose of study drug, approximately 2 years
Cmax: Maximum Plasma Concentration for Alisertib
Time frame: Cycle 1 Days 1 and 7 prior to morning alisertib dose and multiple time-points (up to 12 hours) post-dose
Tmax: Time to First Occurrence of Cmax fo Alisertib
Time frame: Cycle 1 Days 1 and 7 prior to morning alisertib dose and multiple time-points (up to 12 hours) post-dose
AUCt: Area Under the Concentration Time Curve Over the Dosing Interval From Time 0 to Time t for Alisertib
Time frame: Cycle 1 Days 1 and 7 prior to morning alisertib dose and multiple time-points (up to 12 hours) post-dose
Cmax: Maximum Plasma Concentration for Vincristine
Time frame: Cycles 1 and 2 on Day 1 prior to injection of vincristine and multiple time-points (up to 72 hours) post-dose
AUCt: Area Under the Concentration-time Time Curve Over the Dosing Interval From Time 0 to Time t for Vincristine
Time frame: Cycles 1 and 2 on Day 1 prior to injection of vincristine and multiple time-points (up to 72 hours) post-dose
AUC∞: Area Under the Concentration-time Curve From Time 0 to Infinity for Vincristine
Time frame: Cycles 1 and 2 on Day 1 prior to injection of vincristine and multiple time-points (up to 72 hours) post-dose
T1/2: Terminal Disposition Phase Half-life for Vincristine
Time frame: Cycles 1 and 2 on Day prior to injection of vincristine and multiple time-points (up to 72 hours) post-dose
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.
- Derived from this study: PubMed 30082475Kelly KR, Friedberg JW, Park SI, McDonagh K, Hayslip J, Persky D, Ruan J, Puvvada S, Rosen P, Iyer SP, Stefanovic A, Bernstein SH, Weitman S, Karnad A, Monohan G, VanderWalde A, Mena R, Schmelz M, Spier C, Groshen S, Venkatakrishnan K, Zhou X, Sheldon-Waniga E, Leonard EJ, Mahadevan D. Phase I Study of the Investigational Aurora A Kinase Inhibitor Alisertib plus Rituximab or Rituximab/Vincristine in Relapsed/Refractory Aggressive B-cell Lymphoma. Clin Cancer Res. 2018 Dec 15;24(24):6150-6159. doi: 10.1158/1078-0432.CCR-18-0286. Epub 2018 Aug 6.
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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 Monitor study director
Millennium Pharmaceuticals, Inc.
25 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Alisertib (MLN8237), Rituximab and Vincristine in people with Diffuse Large B-Cell Lymphoma and Transformed Follicular Lymphoma, run by Millennium Pharmaceuticals, Inc. at 25 sites in 4 countries.
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 8 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: 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 25 sites in United States, Italy, United Kingdom, Spain. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Number of Participants With Clinically Significant Vital Signs Findings (Treatment Related and Unrelated) [Phase 1] (time frame: First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)). The study lists 7 primary outcomes in all. 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 NCT01397825, 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.