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

Purpose

The overall purpose of the study is to determine if MEDI-551, when used in combination with salvage chemotherapy, Ifosafamide-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	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:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy 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:

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:

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:	January 2019
Estimated Primary Completion Date:	August 2016 (Final data collection date for primary outcome measure)

Arms	Assigned 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 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01453205

Contacts

Contact: Katura Fetterson

301-398-0000

clinicaltrialenquiries@medimmune.com

Show 51 Study Locations

Sponsors and Collaborators

MedImmune LLC

Investigators

Study Director:

Trishna Goswami, MD

MedImmune LLC

More Information

No publications provided

Responsible Party:	MedImmune LLC
ClinicalTrials.gov Identifier:	NCT01453205 History of Changes
Other Study ID Numbers:	CD-ON-MEDI-551-1088
Study First Received:	October 3, 2011
Last Updated:	May 6, 2013
Health Authority:	United States: Food and Drug Administration Canada: Health Canada United States: Institutional Review Board

Keywords provided by MedImmune LLC:

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

Additional relevant MeSH terms:

Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

Lymphoma, Non-Hodgkin
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on May 23, 2013