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

NCT01453205 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CD-ON-MEDI-551-1088
• Study Type: interventional
• Target: 187
• Locations: 11 countries
• Sites: 81

Brief Summary

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.

Conditions

Diffuse Large B-Cell Lymphoma

Keywords

Lymphoma, Non-Hodgkin's Lymphoma, Diffuse Large B-Cell Lymphoma, DLBCL, B-Cell Malignancy, anti-CD19, monoclonal antibody, second line, ASCT, Refractory

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Objective Response Rate is defined as the proportion of participants with a best response of complete response (CR) or partial response (PR) according to the International Working Group criteria. CR is defined as disappearance of all evidence of disease. PR is defined as 50 percent (%) decrease in the sum of the product of the perpendicular diameters (SPD) of up to 6 largest dominant nodal masses and greater than or equal to (\>=) 50% decrease in SPD of spleen/liver nodules.

  From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)

Secondary Outcomes (15)

• Progression-Free Survival (PFS)

  From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)

• Event-Free Survival (EFS)

  From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)

• Overall Survival (OS)

  From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)

• Time to Progression (TTP)

  From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)

• Time to Response (TTR)

  From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)

Study Arms (3)

Rituximab+ ICE/DHAP

ACTIVE COMPARATOR

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.

Drug: Rituximab; Drug: ICE; Drug: DHAP; Procedure: Autologous Stem Cell Transplant (ASCT)

MEDI-551 2 mg/kg + ICE/DHAP

EXPERIMENTAL

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.

Drug: MEDI-551 2 mg/kg; Drug: ICE; Drug: DHAP; Procedure: Autologous Stem Cell Transplant (ASCT)

MEDI-551 4 mg/kg + ICE/DHAP

EXPERIMENTAL

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.

Drug: ICE; Drug: DHAP; Procedure: Autologous Stem Cell Transplant (ASCT); Drug: MEDI-551 4 mg/kg

Interventions

MEDI-551 2 mg/kg 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).

Also known as: Inebilizumab

MEDI-551 2 mg/kg + ICE/DHAP

Rituximab 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).

Also known as: Rituxan; MabThera

Rituximab+ ICE/DHAP

ICE 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.

MEDI-551 2 mg/kg + ICE/DHAP; MEDI-551 4 mg/kg + ICE/DHAP; Rituximab+ ICE/DHAP

DHAP 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.

MEDI-551 2 mg/kg + ICE/DHAP; MEDI-551 4 mg/kg + ICE/DHAP; Rituximab+ ICE/DHAP

Autologous Stem Cell Transplant (ASCT) 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; MEDI-551 4 mg/kg + ICE/DHAP; Rituximab+ ICE/DHAP

MEDI-551 4 mg/kg 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).

Also known as: Inebilizumab

MEDI-551 4 mg/kg + ICE/DHAP

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (81)

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Birmingham, Alabama, 35061, United States

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Burbank, California, 91501, United States

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Palm Springs, California, 92262, United States

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Sylmar, California, 91342, United States

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Atlanta, Georgia, 30342, United States

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Westwood, Kansas, 66205, United States

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Hazard, Kentucky, 41701, United States

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Lafayette, Louisiana, 70503, United States

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Shreveport, Louisiana, 71103, United States

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Baltimore, Maryland, 21215, United States

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Minneapolis, Minnesota, 55455, United States

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Rochester, Minnesota, 55905, United States

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Kansas City, Missouri, 64111, United States

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Kansas City, Missouri, 66160, United States

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St Louis, Missouri, 63110, United States

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The Bronx, New York, 10466, United States

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Fargo, North Dakota, 58102, United States

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Dayton, Ohio, 45403, United States

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Newark, Ohio, 43055, United States

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Sylvania, Ohio, 43560, United States

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Hershey, Pennsylvania, 17033, United States

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Philadelphia, Pennsylvania, 19104, United States

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Charleston, South Carolina, 29425, United States

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Knoxville, Tennessee, 37909, United States

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Dallas, Texas, 75246, United States

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Houston, Texas, 77030, United States

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Lubbock, Texas, 79410, United States

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Morgantown, West Virginia, 26505, United States

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Milwaukee, Wisconsin, 53266, United States

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Saint John, New Brunswick, E2E5A2, Canada

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Halifax, Nova Scotia, B3H 1V7, Canada

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Greenfield Park, Quebec, J4V 2H1, Canada

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Brno, 12808, Czechia

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Prague, 12808, Czechia

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Bordeaux, 33300, France

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Le Mans, 72000, France

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Libourne, 33205, France

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Marseille, 13005, France

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Marseille, 13273, France

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Pessac, 33604, France

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Rouen, 76100, France

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Tours, 37100, France

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Berlin, 10967, Germany

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Frankfurt, 65929, Germany

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Mainz, 55131, Germany

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München, 80804, Germany

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Tübingen, 72076, Germany

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Würzburg, 97080, Germany

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Budapest, 01083, Hungary

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Debrecen, 04032, Hungary

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Győr, 09200, Hungary

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Kaposvár, 07400, Hungary

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Ashkelon, 78278, Israel

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Haifa, 31999, Israel

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Jerusalem, Israel

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Tel Aviv, 64239, Israel

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Gdynia, 81-519, Poland

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Lublin, 20081, Poland

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Nizhny Novgorod, 603126, Russia

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Saint Petersburg, 191024, Russia

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Saint Petersburg, 197341, Russia

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Barcelona, 08041, Spain

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Cadiz, 11009, Spain

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Girona, 17007, Spain

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L'Hospitalet de Llobregat, 08907, Spain

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Madrid, 28025, Spain

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Majadahonda, 28222, Spain

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Málaga, 29010, Spain

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Pamplona, 31008, Spain

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Salamanca, 37007, Spain

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San Sebastián de los Reyes, 28702, Spain

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Seville, 41013, Spain

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Seville, 41014, Spain

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Valencia, 46015, Spain

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Valencia, 46017, Spain

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Valencia, 46026, Spain

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Izmir, 35100, Turkey (Türkiye)

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Izmir, 35340, Turkey (Türkiye)

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Kurupelit, 55139, Turkey (Türkiye)

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Malatya, 44100, Turkey (Türkiye)

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Talas, 38280, Turkey (Türkiye)

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MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma; Lymphoma, Non-Hodgkin

Interventions

inebilizumab; Rituximab; Ice

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Water; Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds; Environment; Ecological and Environmental Phenomena; Biological Phenomena; Weather; Meteorological Concepts; Environment and Public Health

Results Point of Contact

• Title: Mohammed Dar
• Organization: MedImmune, LLC

information.center@astrazeneca.com

301-398-4095

Study Officials

• MedImmune LLC

  MedImmune LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2011
• First Posted: October 17, 2011
• Study Start: February 27, 2012
• Primary Completion: July 11, 2016
• Study Completion: July 11, 2016
• Last Updated: March 12, 2018
• Results First Posted: March 12, 2018

Record last verified: 2018-02

Locations

PL (2); ES (15); FR (8); IL (4); CA (3); US (29); DE (6); HU (4); RU (3); TU (5); CZ (2)