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

NCT ID: NCT01453205

Last Updated: 2018-03-12

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

187 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-02-27

Study Completion Date

2016-07-11

Brief Summary

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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.

Detailed Description

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Conditions

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Diffuse Large B-Cell Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Rituximab+ ICE/DHAP

Participants will receive Rituximab in combination with ifosfamide + carboplatin + etoposide (ICE) or dexamethasone + cisplatin + cytarabine (DHAP) for 3 cycles (21-day cycles) and will followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). Rituximab (375 mg/m\^2) will be administered intravenous (IV) on 2 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of rituximab, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of rituximab, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.

Group Type ACTIVE_COMPARATOR

Rituximab

Intervention Type DRUG

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).

ICE

Intervention Type DRUG

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.

DHAP

Intervention Type DRUG

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.

Autologous Stem Cell Transplant (ASCT)

Intervention Type PROCEDURE

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

MEDI-551 2 mg/kg + ICE/DHAP

Participants will receive MEDI-551 (2 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and will be followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (2 mg/kg) will be administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.

Group Type EXPERIMENTAL

MEDI-551 2 mg/kg

Intervention Type DRUG

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).

ICE

Intervention Type DRUG

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.

DHAP

Intervention Type DRUG

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.

Autologous Stem Cell Transplant (ASCT)

Intervention Type PROCEDURE

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

MEDI-551 4 mg/kg + ICE/DHAP

Participants will receive MEDI-551 (4 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and will be followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (4 mg/kg) will be administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.

Group Type EXPERIMENTAL

ICE

Intervention Type DRUG

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.

DHAP

Intervention Type DRUG

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.

Autologous Stem Cell Transplant (ASCT)

Intervention Type PROCEDURE

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

MEDI-551 4 mg/kg

Intervention Type DRUG

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).

Interventions

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MEDI-551 2 mg/kg

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).

Intervention Type 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).

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

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.

Intervention Type PROCEDURE

MEDI-551 4 mg/kg

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).

Intervention Type DRUG

Other Intervention Names

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Inebilizumab Rituxan; MabThera Inebilizumab

Eligibility Criteria

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Inclusion Criteria

* Histologically confirmed aggressive B-cell DLBCL, including FL transforming to DLBCL \& Grade III FL
* Relapsed from or refractory to at least one treatment containing rituximab or another anti-CD20 based immunotherapy combined with anthracycline- or anthracenedione-based chemotherapy
* Eligible for ASCT
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
* Life expectancy of ≥ 12 weeks
* Adequate hematological function

Exclusion Criteria

* Any chemotherapy, radiotherapy, immunotherapy, biologic, investigational or hormonal therapy for treatment of lymphoma within 28 days prior to treatment
* Previous cancer therapy for DLBCL other than anthracycline- or anthracenedione based chemoimmunotherapy, monotherapy rituximab prior to first line therapy and/or as a maintenance therapy, or limited field radiotherapy
* Prior autologous or allogeneic SCT
* New York Heart Association ≥ Class II congestive heart failure; Clinically significant abnormality on ECG
* History of other invasive malignancy within 5 years except for localized/in situ, carcinomas such as cervical carcinoma in situ.
* Evidence of active infection
* Documented current central nervous system involvement by leukemia or lymphoma
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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MedImmune LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MedImmune LLC

Role: STUDY_DIRECTOR

MedImmune LLC

Locations

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Birmingham, Alabama, United States

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Burbank, California, United States

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Palm Springs, California, United States

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Sylmar, California, United States

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Atlanta, Georgia, United States

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Westwood, Kansas, United States

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Hazard, Kentucky, United States

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Lafayette, Louisiana, United States

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Shreveport, Louisiana, United States

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Baltimore, Maryland, United States

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Minneapolis, Minnesota, United States

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Rochester, Minnesota, United States

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Kansas City, Missouri, United States

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Kansas City, Missouri, United States

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St Louis, Missouri, United States

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The Bronx, New York, United States

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Fargo, North Dakota, United States

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Dayton, Ohio, United States

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Newark, Ohio, United States

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Sylvania, Ohio, United States

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Hershey, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Charleston, South Carolina, United States

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Knoxville, Tennessee, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Lubbock, Texas, United States

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Morgantown, West Virginia, United States

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Milwaukee, Wisconsin, United States

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Saint John, New Brunswick, Canada

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Halifax, Nova Scotia, Canada

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Greenfield Park, Quebec, Canada

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Brno, , Czechia

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Prague, , Czechia

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Bordeaux, , France

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Le Mans, , France

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Libourne, , France

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Marseille, , France

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Marseille, , France

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Pessac, , France

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Rouen, , France

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Tours, , France

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Berlin, , Germany

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Frankfurt, , Germany

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Mainz, , Germany

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München, , Germany

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Tübingen, , Germany

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Würzburg, , Germany

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Budapest, , Hungary

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Debrecen, , Hungary

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Győr, , Hungary

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Kaposvár, , Hungary

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Ashkelon, , Israel

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Haifa, , Israel

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Jerusalem, , Israel

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Tel Aviv, , Israel

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Gdynia, , Poland

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Lublin, , Poland

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Nizhny Novgorod, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Barcelona, , Spain

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Cadiz, , Spain

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Girona, , Spain

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L'Hospitalet de Llobregat, , Spain

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Madrid, , Spain

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Majadahonda, , Spain

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Málaga, , Spain

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Pamplona, , Spain

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Salamanca, , Spain

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San Sebastián de los Reyes, , Spain

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Seville, , Spain

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Seville, , Spain

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Valencia, , Spain

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Valencia, , Spain

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Valencia, , Spain

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Izmir, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Kurupelit, , Turkey (Türkiye)

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Malatya, , Turkey (Türkiye)

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Talas, , Turkey (Türkiye)

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Countries

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United States Canada Czechia France Germany Hungary Israel Poland Russia Spain Turkey (Türkiye)

Other Identifiers

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CD-ON-MEDI-551-1088

Identifier Type: -

Identifier Source: org_study_id

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