A Phase 2, Multicenter, Randomized, Open-label Study of MEDI-551 in Adults With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

This study is currently recruiting participants.
Verified June 2012 by MedImmune LLC

First Received on October 3, 2011.  
Last Updated on June 7, 2012  
History of Changes
This Clinical Trial Sponsored By: MedImmune LLC
Information provided by (Responsible Party): MedImmune LLC
ClinicalTrials.gov Identifier: NCT01453205
 

Purpose for Clinical Trial

The overall purpose of the study is to determine if MEDI-551, when used in combination with salvage chemotherapy, Ifosfamide-carboplatin-etoposide (ICE) or Dexamethasone-cytarabine (DHAP) in patients with relapsed or refractory DLBCL who are eligible for Autologous Stem Cell Transplant (ASCT), has superior efficacy compared to rituximab in the same population.

Condition Study Intervention Phase
Diffuse Large B-Cell Lymphoma (DLBCL) Drug: MEDI-551
Drug: Rituximab
Drug: ICE
Drug: DHAP
Procedure: Autologous Stem Cell Transplant (ASCT)
Phase 2

Study Type: Study Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Study Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Randomized Open-label Study of MEDI-551 in Adults With Relapsed or Refractory DLBCL

Resource links provided by NLM:

MedlinePlus related topics:
Lymphoma
Drug Information available for:
Rituximab

U.S. FDA Resources

Further study details as provided by MedImmune LLC:

Primary Outcome Measures For Clinical Trial:

  • Overall Response Rate (ORR) [ Time Frame: Study Day 1080 ] [ Designated as safety issue: No ]
    Evaluation of the overall response rate (ORR), including Partial Response (PR) and Complete Response (CR), of subjects treated with MEDI-551 when used in combination with ICE or DHAP versus rituximab in combination with ICE or DHAP in subjects with relapsed or refractory DLBCL.

Secondary Outcome Measures For Clinical Trial:

  • Antitumor Activity [ Time Frame: Study Day 1080 ] [ Designated as safety issue: No ]
    Includes complete response rate, Minimal residual disease negative complete response rate, time to response (TTR), time to progression (TTP), progression-free survival (PFS), and overall survival (OS)

  • Acceptable Dose [ Time Frame: Study Day 42 ] [ Designated as safety issue: Yes ]
    Determination of an acceptable dose for MEDI-551 when used in combination with ICE or DHAP; Benefit/Risk Analysis of Safety and Efficacy to be determined

  • Safety and Tolerability [ Time Frame: Study Day 1080 ] [ Designated as safety issue: Yes ]
    The safety endpoints include Adverse Events (AEs), Serious Adverse Events (SAEs) occurring during the protocol-specified reporting period and changes in clinical laboratory evaluations, Electrocardiogram (ECGs), vital signs, and weight from baseline.

  • Immunogenicity (IM) [ Time Frame: Up to Study Day 1080 ] [ Designated as safety issue: Yes ]
    Number and percentage of subjects who develop detectable anti-drug antibodies

  • Pharmacokinetics (PK) [ Time Frame: Study Day 1; Study Day 8; Study Day 12; Study Day 19; Study Day 26; Study Day 54; Study Day 110; Study Day 138; Study Day 166 ] [ Designated as safety issue: No ]
    Area Under Curve, CMAX, T1-half

Estimated Enrollment: 170
Study Start Date: February 2012
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)

Arms

Assigned Study Interventions

Experimental: MEDI-551 (dose level 1) + ICE/DHAP Drug: MEDI-551

MEDI-551 at the assigned dose will be administered via Intravenous (IV) infusion. Subjects will receive 3 cycles of M-ICE or M-DHAP unless CR is achieved at the end of Cycle 2, disease progression is noted at the end of Cycle 2, or a significant/serious drug related toxicity occurs (as per the opinion of the investigator).

Drug: ICE

ICE will be administered via IV infusion as follows: ifosfamide 5 g/m2 continuously for 24 hours with mesna on Days 2 and 3; carboplatin AUC=5 mg/mL x min [800 mg maximum) on Day 2; etoposide 100 mg/m2 on Days 1, 2, and 3) in 21-day cycles.

Drug: DHAP

DHAP will be administered via IV infusion as follows: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m2 continuously for 24 hours on Day 1 of dosing cycle; cytarabine 2 g/m2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.

Procedure: Autologous Stem Cell Transplant (ASCT)

Subjects who achieve CR or PR will undergo stem cell harvest and autologous stem cell transplantation (ASCT) following standard institutional protocols.
Experimental: MEDI-551 (dose level 2) + ICE/DHAP Drug: MEDI-551

MEDI-551 at the assigned dose will be administered via Intravenous (IV) infusion. Subjects will receive 3 cycles of M-ICE or M-DHAP unless CR is achieved at the end of Cycle 2, disease progression is noted at the end of Cycle 2, or a significant/serious drug related toxicity occurs (as per the opinion of the investigator).

Drug: ICE

ICE will be administered via IV infusion as follows: ifosfamide 5 g/m2 continuously for 24 hours with mesna on Days 2 and 3; carboplatin AUC=5 mg/mL x min [800 mg maximum) on Day 2; etoposide 100 mg/m2 on Days 1, 2, and 3) in 21-day cycles.

Drug: DHAP

DHAP will be administered via IV infusion as follows: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m2 continuously for 24 hours on Day 1 of dosing cycle; cytarabine 2 g/m2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.

Procedure: Autologous Stem Cell Transplant (ASCT)

Subjects who achieve CR or PR will undergo stem cell harvest and autologous stem cell transplantation (ASCT) following standard institutional protocols.
Active Comparator: Rituximab + ICE/DHAP Drug: Rituximab

Rituximab at 375 mg/m2 will be administered via IV infusion 2 days before the start of Cycle 1 and on Day 1 of each cycle. The infusion time for rituximab will be 50 400 mg/hr, depending on subject’s tolerance. Subjects will receive 3 cycles of Rituximab with Ice (R ICE) or Rituximab with DHAP (R-DHAP) unless CR is achieved at the end of Cycle 2, disease progression is noted at the end of Cycle 2, or a significant/serious drug related toxicity occurs (as per the opinion of the investigator).
Other Name: Rituxan; MabThera

Drug: ICE

ICE will be administered via IV infusion as follows: ifosfamide 5 g/m2 continuously for 24 hours with mesna on Days 2 and 3; carboplatin AUC=5 mg/mL x min [800 mg maximum) on Day 2; etoposide 100 mg/m2 on Days 1, 2, and 3) in 21-day cycles.

Drug: DHAP

DHAP will be administered via IV infusion as follows: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m2 continuously for 24 hours on Day 1 of dosing cycle; cytarabine 2 g/m2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.

Procedure: Autologous Stem Cell Transplant (ASCT)

Subjects who achieve CR or PR will undergo stem cell harvest and autologous stem cell transplantation (ASCT) following standard institutional protocols.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed aggressive B-cell DLBCL, including FL transforming to DLBCL & Grade III FL
  • Relapsed from or refractory to at least

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