MLN8237 in Patients With Relapsed or Refractory Aggressive B-Cell Lymphoma Treated With Rituximab & Vincristine

This study is currently recruiting participants.
Verified May 2012 by Millennium Pharmaceuticals, Inc.

First Received on July 17, 2011.  
Last Updated on May 17, 2012  
History of Changes
This Clinical Trial Sponsored By: Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party): Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01397825
 

Purpose for Clinical Trial

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:

Part 1, Clinical Trial Phase 1: Safety lead-in cohort to evaluate alisertib (MLN8237) and rituximab.

Part 2, Phase 1: 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.

Condition Study Intervention Phase
Diffuse Large B-Cell Lymphoma
Transformed Follicular Lymphoma
Mantle Cell Lymphoma
Burkitt’s Lymphoma
Drug: Alisertib (MLN8237) + Rituximab + Vincristine Phase 1
Phase 2

Study Type: Study Interventional
Study Design: Study Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics:
Lymphoma
Drug Information available for:
Vincristine sulfate
Rituximab

U.S. FDA Resources

Further study details as provided by Millennium Pharmaceuticals, Inc.:

Primary Outcome Measures For Clinical Trial:

  • Recommended phase 2 dose and schedule of alisertib (MLN8237) in combination with rituximab based on safety and tolerability (phase 1, part 1) [ Time Frame: From the screening period to 30 days after the last dose of alisertib (MLN8237), approximately 6 months ] [ Designated as safety issue: Yes ]
    Vital signs, electrocardiograms (ECGs), multigated acquisition (MUGA)/ echocardiogram (ECHO), physical examination, laboratory tests, and adverse events

  • Recommended phase 2 dose and schedule of alisertib (MLN8237) in combination with rituximab and vincristine based on safety and tolerability (phase 1, part 2) [ Time Frame: From the screening period to 30 days after the last dose of alisertib (MLN8237), approximately 6 months ] [ Designated as safety issue: Yes ]
    Vital signs, electrocardiograms (ECGs), multigated acquisition (MUGA)/ echocardiogram (ECHO), physical examination, laboratory tests, and adverse events

  • Number of patients with overall response (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 ] [ Designated as safety issue: No ]
    Complete response + partial response

Secondary Outcome Measures For Clinical Trial:

  • Number of patients with overall response (phase 1, part 1) [ 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 ] [ Designated as safety issue: No ]
    Complete response + partial response

  • Number of patients with overall response (phase 1, part 1 & 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 ] [ Designated as safety issue: No ]
    Complete response + partial response

  • Number of patients with complete response, duration of response, and progression free survival (phase 2) [ Time Frame: Duration of study until disease progression, approximately 2 years ] [ Designated as safety issue: No ]
  • Number of adverse events and results of vital signs, electrocardiograms (ECGs), multigated acquisition (MUGA)/ echocardiogram (ECHO), physical examination and laboratory tests (phase 2) [ Time Frame: From screening period to 30 days after last dose of study drug, approximately 2 years ] [ Designated as safety issue: Yes ]
    Safety and tolerability of alisertib (MLN8237) treatment

  • Maximum plasma concentration (Cmax) (phase 1, parts 1&2) [ Time Frame: Cycle 1 Day 1 and Day 7, then Day 8 of each treatment cycle, approximately 6 months ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters of alisertib (MLN8237)

  • Time to maximum plasma concentration (Tmax) (phase 1, parts 1&2) [ Time Frame: Cycle 1 Day 1 and Day 7, then Day 8 of each treatment cycle, approximately 6 months ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters of alisertib (MLN8237)

  • Area under the plasma concentration versus time curve over the dosing interval (AUC0-τ) (phase 1, parts 1&2) [ Time Frame: Cycle 1 Day 1 and Day 7, then Day 8 of each treatment cycle, approximately 6 months ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters of alisertib (MLN8237)

  • Maximum plasma concentration (phase 1, part 2) [ Time Frame: Days 1-4 of Cycle 2 ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters of vincristine

  • Area under the plasma concentration vs time curve from time zero to the time of last quantifiable concentration (phase 1, part 2) [ Time Frame: Days 1-4 of Cycle 2 ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters of vincristine

  • Area under the plasma concentration vs time curve from time zero to infinity (phase 1, part 2) [ Time Frame: Days 1-4 of Cycle 2 ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters of vincristine

  • Half-life of vincristine (phase 1, part 2) [ Time Frame: Days 1-4 of Cycle 2 ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters of vincristine

Estimated Enrollment: 100
Study Start Date: August 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)

Arms

Assigned Study Interventions

Experimental: Alisertib (MLN8237) + Rituximab + Vincristine Drug: Alisertib (MLN8237) + Rituximab + Vincristine

Phase 1, Part 1: Safety lead-in cohort combining alisertib (MLN8237) as an enteric coated tablet (ECT) orally twice/day Days 1-7 & rituximab as an intravenous (IV) infusion on Day 1 in a 21 Day cycle for up to 8 cycles

Phase 1, Part 2: Alisertib (MLN8237) as an ECT orally twice/day Days 1-7 & rituximab as an IV infusion on Day 1 & vincristine IV Days 1 & 8 in a 21 Day cycle for up to 8 cycles

Phase 2: Alisertib (MLN8237) as an ECT orally twice/day Days 1-7 & rituximab as an IV infusion on Day 1 & vincristine IV Days 1 & 8 in a 21 Day cycle for up to 8 cycles

Following 8 cycles of treatment (or early discontinuation of rituximab) all patients with documented disease response or stabilization may continue with alisertib (MLN8237) single-agent therapy up to 2 years

  Eligibility

Ages

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