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Study of Alisertib (MLN8237) in Adults With Aggressive Non-Hodgkin's Lymphoma

Primary Purpose

Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, Burkitt's Lymphoma

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Alisertib

About this trial

This is an interventional treatment trial for Diffuse Large B-cell Lymphoma focused on measuring MLN8237, Alisertib, Drug therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Each participant must meet all of the following inclusion criteria to be enrolled in the study:

Participant must have histological or cytological diagnosis of a hematological malignancy of the following types that has relapsed or was refractory to prior therapy:
- Diffuse large B-cell lymphoma
- Mantle cell lymphoma
- Burkitt's lymphoma
- Precursor B-lymphoblastic leukemia/lymphoma
- T-cell lymphoma, excluding primary cutaneous T-cell lymphoma
- Transformed follicular lymphoma with ≥ 50% diffuse large cell component.
Male or female participants 18 years or older.
Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
Measurable disease.

Exclusion criteria include the following:

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.
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).

Sites / Locations

Hematology Oncology Associates, Virtua Memorial Hospital Burlington County

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Alisertib 50 mg

Arm Description

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).

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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.

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.

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).

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).

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.

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.

Full Information

NCT ID

NCT00807495

First Posted

December 11, 2008

Last Updated

February 27, 2018

Sponsor

Millennium Pharmaceuticals, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT00807495

Brief Title

Study of Alisertib (MLN8237) in Adults With Aggressive Non-Hodgkin's Lymphoma

Official Title

A Phase 2 Trial of MLN8237, an Oral Aurora A Kinase Inhibitor, in Adult Patients With Aggressive Non-Hodgkin's Lymphoma

Study Type

Interventional

2. Study Status

Record Verification Date

February 2018

Overall Recruitment Status

Completed

Study Start Date

February 10, 2009 (Actual)

Primary Completion Date

January 4, 2011 (Actual)

Study Completion Date

February 13, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Millennium Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

48 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Alisertib 50 mg

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Alisertib

Other Intervention Name(s)

MLN8237

Intervention Description

Alisertib capsules

Primary Outcome Measure Information:

Title

Best Overall Response Rate Based on Investigator's Assessment (Applying the IWG 2007 Response Criteria)

Description

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)

Secondary Outcome Measure Information:

Title

Time to Progression (TTP)

Description

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)

Title

Progression Free Survival (PFS)

Description

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.

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)

Title

Duration of Response (DOR)

Description

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)

Title

Number of Participants With Treatment-Emergent Adverse Events

Description

Time Frame

First dose of study drug to 30 days after last dose (Up to 25 months)

Title

Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events

Description

Time Frame

First dose of study drug to 30 days after last dose (Up to 25 months)

Title

Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events

Description

Time Frame

First dose of study drug to 30 days after last dose (Up to 25 months)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Each participant must meet all of the following inclusion criteria to be enrolled in the study: Participant must have histological or cytological diagnosis of a hematological malignancy of the following types that has relapsed or was refractory to prior therapy: Diffuse large B-cell lymphoma Mantle cell lymphoma Burkitt's lymphoma Precursor B-lymphoblastic leukemia/lymphoma T-cell lymphoma, excluding primary cutaneous T-cell lymphoma Transformed follicular lymphoma with ≥ 50% diffuse large cell component. Male or female participants 18 years or older. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. Measurable disease. Exclusion criteria include the following: 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. 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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director Clinical Science

Organizational Affiliation

Millennium Pharmaceuticals, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Hematology Oncology Associates, Virtua Memorial Hospital Burlington County

City

Mount Holly

State/Province

New Jersey

ZIP/Postal Code

08060

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

17242396

Citation

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.

Results Reference

result

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Study of Alisertib (MLN8237) in Adults With Aggressive Non-Hodgkin's Lymphoma

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