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MEDI-551/kg

Phase 2

Diffuse Large B-Cell Lymphoma | Small molecule | Oncology |AstraZeneca PLC|Last Updated: Mar 12, 2018

Success Probability

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Trial Design

RandomizedACTIVE_CONTROLLEDDMC
Total Trials1
Total Enrollment187

FDA Designations

No designations recorded

Clinical trial landscape

MEDI-551/kg · 2 trials · 2 indications

Phase 2 1Phase 1 1
NCT01453205A Phase 2, Multicenter, Randomized, Open-label Study of MEDI-551 in Adults With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)Diffuse Large B-Cell Lymphoma
COMPLETED187 Analytics
PHASE2COMPLETED
A Phase 2, Multicenter, Randomized, Open-label Study of MEDI-551 in Adults With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Diffuse Large B-Cell LymphomaUnlock trial analytics

Study Endpoints

Primary Endpoints

Objective Response Rate (ORR)
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)

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.

Maximum Tolerated Dose (MTD) of MEDI-551
Day 1 to Day 28 of Cycle 1 (28-day cycle)

The Maximum Tolerated Dose, defined as the highest dose where less than or equal to (\<= 1) out of 6 subjects experiences a dose limiting toxicity (DLT) during the DLT evaluation period (Day 1 to Day 28 of Cycle 1) or the highest protocol specified dose not exceeding MTD.

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Treatment-Emergent Serious Adverse Events (TESAEs)
From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)

An Adverse Event (AE) is any unfavourable and unintended signs, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. SAE is any AE that resulted in death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, life-threatening, a congenital anomaly/birth defect, or an important medical event. TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 90 days after the end of treatment (EOT).

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Clinical Laboratory Abnormalities
From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)

An abnormal laboratory findings that was judged by the investigator to be medically significant was reported as an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, for the period extending to 90 days after the end of study drug.

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Related to Vital Signs, Physical Findings Abnormalities
From treatment administration to 90-days after last dose of study drug (up to approximately 2 years)

Vital signs included parameters such as blood pressure, temperature, respiratory rate, and pulse oximetry. An abnormal vital signs and physical findings that was judged by the investigator to be medically significant was reported an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, for the period extending to 90 days after the end of study treatment.

Number of Participants With Best Overall Response
Day 1 to Day 28 of Cycle 13 (28-day cycle)

The best overall response was calculated, based upon the disease assessments recorded during the study visits, and summarized with the number of participants for the following categories: complete response (disappearance of all evidence of disease), partial response (regression of measurable disease and no new sites), stable disease (SD), progessive disease (PD), and non- evaluable (NE).

Secondary Endpoints

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)
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Rituximab+ ICE/DHAPACTIVE_COMPARATORParticipants 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.
MEDI-551 2 mg/kg + ICE/DHAPEXPERIMENTALParticipants 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.
MEDI-551 4 mg/kg + ICE/DHAPEXPERIMENTALParticipants 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.
MEDI-551 12 mg/kg and MEDI0680 2.5 mg/kgEXPERIMENTALParticipants will receive intravenous (IV) infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
MEDI-551 12 mg/kg and MEDI0680 10 mg/kgEXPERIMENTALParticipants will receive IV infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13 (each cycle of 28 days) and IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.

Interventions

NameTypeDescription
MEDI-551 2 mg/kgDRUGMEDI-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).
RituximabDRUGRituximab 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).
ICEDRUGICE 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.
DHAPDRUGDHAP 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)PROCEDURESubjects who achieve CR or PR will undergo stem cell harvest and autologous stem cell transplantation (ASCT) following standard institutional protocols.
MEDI-551 4 mg/kgDRUGMEDI-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).
MEDI-551 12 mg/kgDRUGParticipants will receive intravenous (IV) infusion of MEDI-551 12 mg/kg on Days 1 and 8 of Cycle 1 and Day 1 of Cycle 2 through Cycle 13
MEDI0680 2.5 mg/kgDRUGParticipants will receive IV infusion of MEDI0680 2.5 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
MEDI0680 10 mg/kgDRUGParticipants will receive IV infusion of MEDI0680 10 mg/kg on Days 2 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 through Cycle 13.
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Eligibility Criteria

Age Range18 Years to 99 Years
SexALL
Healthy VolunteersNo
Study Sites81

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 chem...

Countries:United StatesCanadaCzechiaFranceGermanyHungaryIsraelPolandRussiaSpainTurkey (Türkiye)
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Frequently asked questions about MEDI-551/kg

What is MEDI-551 used for?

MEDI-551 is an investigational drug being studied for B-cell malignancies, multiple sclerosis, scleroderma, chronic lymphocytic leukemia (CLL), and relapsed or refractory aggressive B-cell lymphomas. It has been evaluated in clinical trials for these conditions, including diffuse large B-cell lymphoma and scleroderma.

Who makes MEDI-551?

MEDI-551 is being developed by AstraZeneca PLC, a biopharmaceutical company traded on the stock exchange under the ticker symbol AZN. The drug is currently in clinical development and is not approved for any indication.

What phase is MEDI-551 in?

MEDI-551 has completed Phase 1 and Phase 2 clinical trials. It is an investigational drug, meaning it is still in clinical development and has not been approved by regulatory authorities. Its development status is based on completed trials in various conditions.

What clinical trials is MEDI-551 in?

MEDI-551 has been studied in several completed clinical trials. These include NCT00946699 for scleroderma, NCT00983619 for relapsed or refractory advanced B-cell malignancies, NCT01453205 for diffuse large B-cell lymphoma, and NCT02271945 for aggressive B-cell lymphomas in combination with immunomodulating therapies.

Is MEDI-551 the same as any other drug?

MEDI-551 is the primary name used for this investigational drug in clinical trials. No alternative names have been established for MEDI-551 in the available clinical trial information.