A Phase 2, Multicenter, Open-label Study of MEDI-551 in Adults With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

Phase 2

Completed

Conditions: Chronic Lymphocytic Leukemia (CLL)

Interventions: Drug: Rituximab
Drug: Bendamustine
Drug: MEDI-551

Registration Number: NCT01466153

Lead Sponsor: MedImmune LLC

Brief Summary: The overall purpose of the study was to determine if MEDI-551, when used in combination with salvage chemotherapy (bendamustine) in participants with relapsed or refractory CLL who are not eligible for Autologous Stem Cell Transplant (ASCT), had superior efficacy compared to rituximab in the same population.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 183

Inclusion Criteria

Histologically confirmed B-cell Chronic Lymphocytic Leukemia (CLL) according to the National Cancer Institute criteria; Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2; Adequate hematological function

Exclusion Criteria

Any chemotherapy, radiotherapy, immunotherapy, biologic, investigational, or hormonal therapy for treatment of lymphoma within 28 days prior to treatment;
Exposure to bendamustine within the 180 days before study enrollment
Prior autologous or allogeneic stem cell transplantation (SCT);
Clinically significant abnormality on electrocardiogram (ECG) as determined by the treating physician or medical monitor;
History of other invasive malignancy within 5 years except for localized/in situ carcinomas;
Evidence of active infection, Confirmed current central nervous system involvement by leukemia or lymphoma;

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MEDI-551 4 mg/kg + Bendamustine	MEDI-551	MEDI-551 4 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
MEDI-551 2 mg/kg + Bendamustine	MEDI-551	MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
Rituximab + Bendamustine	Rituximab	Rituximab was administered by IV infusion as 375 mg/m\^2 on Day 2 of Cycle 1 and then 500 mg/m\^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.
MEDI-551 2 mg/kg + Bendamustine	Bendamustine	MEDI-551 2 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
MEDI-551 4 mg/kg + Bendamustine	Bendamustine	MEDI-551 4 mg/kg was administered by IV infusion on Days 2 and 8 of Cycle 1 and then on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of MEDI-551 in each cycle.
Rituximab + Bendamustine	Bendamustine	Rituximab was administered by IV infusion as 375 mg/m\^2 on Day 2 of Cycle 1 and then 500 mg/m\^2 on Day 1 of up to 5 subsequent 28-day cycle. Bendamustine was also administered by IV infusion on Day 1 and Day 2 of every cycle (total 6 cycles). Bendamustine was administered before the administration of rituximab in each cycle.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate	From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)	ORR, defined as the proportion of participants with complete response (CR) or partial response (PR) out of total number of participants. Responses were assessed by using National Cancer Institute - Working Group guidelines on CLL.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs) and Adverse Events of Special Interest (AESIs)	From time of consent to 90 days post last dose	An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug (MEDI-551). A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience; persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between administration of study drug and Day 90 that were absent before treatment or that worsened relative to pre-treatment state. An AESIs was one of scientific and medical interest specific to understanding of study product and may have required close monitoring and rapid communication by investigator to the sponsor. Treatment emergent AESIs were collected from the time of dosing through Day 90 after the last dose of study drug.Hepatic function abnormality and infusion reactions resulting in discontinuation were considered as AESIs.
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as AEs	From time of consent to 90 days post last dose	An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as an adverse event. Laboratory evaluations (haematology, serum chemistry and urinalysis) of blood and urine samples were performed.
Number of Participants With Abnormal Vital Signs and Electrocardiogram Reported as AEs	From time of consent to 90 days post last dose	AEs observed in participants with clinically significant ECG abnormalities were assessed.
Complete Response Rate	From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)	Complete response was as per IWG was the complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.
Minimal Residual Disease Negative Complete Response (CR) Rate	From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)	The MRD-negative CR rate was defined as the percentage of participants who achieved CR and became MRD-negative as determined by flow cytometry. CR as per International Working Group (IWG) was complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.
Time to Response	From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)	Time to response was evaluated using the Kaplan-Meier method.
Time to Disease Progression (TTP)	From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)	TTP was defined as the time from onset of treatment with study drug until first evidence/diagnosis of progressive disease or - in the absence of any diagnosis of progressive disease - until the participant´s death.
Progression Free Survival (PFS)	From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)	PFS was measured from the start of treatment with study drug until the first documentation of disease progression or death due to any cause, whichever occurred first. Kaplan-Meier method was used for evaluation.
Overall Survival (OS)	From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)	OS was determined as the time from the start of treatment with study drug until death due to any cause. For participants who were alive at the end of the study or lost to follow-up, OS was censored on the last date when the participant was known be alive. Kaplan-Meier method was used for evaluation.
Number of Participants Who Developed Detectable Anti-drug Antibodies (ADA)	From treatment administration (Day 1) until disease progression, death, initiation of alternative therapy, withdrawal of consent, or end of study (up to 24 months)	A participant was considered ADA-positive across the study if they had a positive reading at any time point during the study.
Terminal Half Life (t1/2) of MEDI-551	Pre-infusion and 1 hour post infusion on Days 2 and 8, Days 15 and 22 of cycle 1	Terminal phase elimination half-life (T1/2) was the time required for half of the drug to be eliminated from the serum.