Clinical trial NCT01453205: A Phase 2, Multicenter, Randomized, Open-label Study of MEDI-551 in Adults With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Official title: A Phase 2 Randomized Open-label Study of MEDI-551 in Adults With Relapsed or Refractory DLBCL
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2011-10-17
Enrollment: 187
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 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:
measure: Progression-Free Survival (PFS)
timeFrame: 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)
measure: Event-Free Survival (EFS)
timeFrame: 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)
measure: Overall Survival (OS)
timeFrame: 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)
measure: Time to Progression (TTP)
timeFrame: 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)
measure: Time to Response (TTR)
timeFrame: 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)
measure: Duration of Response (DR)
timeFrame: 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)
measure: Number of Participants With Best Overall Response Assessed by Blinded Independent Central Review (BICR)
timeFrame: 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)
measure: Acceptable Dose of MEDI-551
timeFrame: After the administration of the first dose of MEDI-551 (7 days before the Cycle 1) to last dose of MEDI-551 (Cycle 3 Day 1) (each cycle of 21 days)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: 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)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results
timeFrame: 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)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
timeFrame: 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)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities
timeFrame: 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)
measure: Number of Participants Who Developed Detectable MEDI-551 Anti-drug Antibodies (ADA)
timeFrame: 7 days before the start of Cycle 1, Day 1 of each subsequent Cycle, EOT, and post EOT on Days 30, 60, 90 and 270 (up to 36 months from the randomization of last participant)
measure: Mean Serum Concentration of MEDI-551
timeFrame: Cycle 1 Day -7 Post dose, pre-dose and postdose on Day 1, post-dose on Days 4, 8, 15 of Cycle 1, pre-dose and postdose on Day 1 of Cycle 2 and Cycle 3
measure: Half-life (T1/2) of MEDI-551
timeFrame: Cycle 1 and EOT (Day 21 of Cycle 3 [each cycle of 21 days] or earlier cycles if treatment stopped before Cycle 3)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Burbank
country: United States
facility: Research Site
state: California
city: Palm Springs
country: United States
facility: Research Site
state: California
city: Sylmar
country: United States
facility: Research Site
state: California
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Westwood
country: United States
facility: Research Site
state: Kansas
city: Hazard
country: United States
facility: Research Site
state: Kentucky
city: Lafayette
country: United States
facility: Research Site
state: Louisiana
city: Shreveport
country: United States
facility: Research Site
state: Louisiana
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: Kansas City
country: United States
facility: Research Site
state: Missouri
city: Kansas City
country: United States
facility: Research Site
state: Missouri
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Bronx
country: United States
facility: Research Site
state: New York
city: Fargo
country: United States
facility: Research Site
state: North Dakota
city: Dayton
country: United States
facility: Research Site
state: Ohio
city: Newark
country: United States
facility: Research Site
state: Ohio
city: Sylvania
country: United States
facility: Research Site
state: Ohio
city: Hershey
country: United States
facility: Research Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Charleston
country: United States
facility: Research Site
state: South Carolina
city: Knoxville
country: United States
facility: Research Site
state: Tennessee
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Lubbock
country: United States
facility: Research Site
state: Texas
city: Morgantown
country: United States
facility: Research Site
state: West Virginia
city: Milwaukee
country: United States
facility: Research Site
state: Wisconsin
city: St. John
country: Canada
facility: Research Site
state: New Brunswick
city: Halifax
country: Canada
facility: Research Site
state: Nova Scotia
city: Greenfield Park
country: Canada
facility: Research Site
state: Quebec
city: Brno
country: Czechia
facility: Research Site
city: Praha 2
country: Czechia
facility: Research Site
city: Praha
country: Czechia
facility: Research Site
city: Bordeaux
country: France
facility: Research Site
city: Le Mans
country: France
facility: Research Site
city: Libourne Cedex
country: France
facility: Research Site
city: Marseille
country: France
facility: Research Site
city: Marseille
country: France
facility: Research Site
city: Pessac
country: France
facility: Research Site
city: Rouen
country: France
facility: Research Site
city: Tours
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Frankfurt
country: Germany
facility: Research Site
city: Mainz
country: Germany
facility: Research Site
city: Muenchen
country: Germany
facility: Research Site
city: Tuebingen
country: Germany
facility: Research Site
city: Wuerzburg
country: Germany
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Gyor
country: Hungary
facility: Research Site
city: Kaposvar
country: Hungary
facility: Research Site
city: Ashkelon
country: Israel
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Tel Aviv
country: Israel
facility: Research Site
city: Gdynia
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Nizhny Novgorod
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Cadiz
country: Spain
facility: Research Site
city: Girona
country: Spain
facility: Research Site
city: L'Hospitalet de Llobregat
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Majadahonda
country: Spain
facility: Research Site
city: Malaga
country: Spain
facility: Research Site
city: Pamplona
country: Spain
facility: Research Site
city: Salamanca
country: Spain
facility: Research Site
city: San Sebastian de los Reyes
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Kurupelit
country: Turkey
facility: Research Site
city: Malatya
country: Turkey
facility: Research Site
city: Talas
country: Turkey
facility: Research Site
Study officials:
affiliation: MedImmune LLC
name: MedImmune LLC
role: STUDY_DIRECTOR
References: