A Phase 1, Dose-escalation Study of MEDI-551 in Japanese Adult Patients With Relapsed or Refractory Advanced B-cell Malignancies

A Phase 1, Dose-escalation Study of MEDI-551, a Humanized Monoclonal Antibody Directed Against CD19, in Japanese Adult Patients With Relapsed or Refractory Advanced B-cell Malignancies

The primary objective of this study is to evaluate the safety and tolerability of MEDI-551 in Japanese patients with relapsed or refractory advanced B-cell malignancies.

Study Overview

• Status: Completed
• Conditions: Blood Cancer; Advanced B Cell Malignancies
• Intervention / Treatment: Drug: MEDI-551

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka-shi, Japan
    • Research Site
  • Isehara-shi, Japan
    • Research Site
  • Nagoya-shi, Japan
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Japanese men or women at least 20 years of age
• Histologically confirmed CLL (excluding small lymphocytic lymphoma (SLL)), DLBCL, FL, or MM.
• Karnofsky Performance Status ≥70;
• Life expectancy of ≥12 weeks

Exclusion Criteria:

• Any available standard line of therapy known to be life-prolonging or life-saving
• Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy for treatment of cancer
• Previous therapy directed against CD19, such as monoclonal antibodies or MAb conjugates

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MEDI-551	Drug: MEDI-551; MEDI-551 will be administered by intravenous infusion at dose of 2, 4 or 8 mg/kg once per week on Days 1 and 8 in the first cycle and then once every 28 days at the start of each subsequent cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Adverse Events	From baseline to 30 days after the last dose of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Dose Limiting Toxicities	A MEDI-551 treatment-related AE of any toxicity grade that lead to an inability to receive a full cycle (2 doses) of MEDI-551, or, any Grade 3 or higher toxicity that could not be reasonably ascribed to another cause, such as disease progression or accident.	From baseline to 28 days after the first dose of study drug
Maximum Tolerated Dose	A dose was considered non-tolerated and dose escalation stopped if ≥2 of up to 6 evaluable patients experienced a DLT at any dose level. MTD is the last dose level before the non-tolerated dose.	From baseline to 28 days after the first dose of study drug
MEDI-551 Trough Concentration Levels at Day 0 (Pre-dose)	Lower limit of quantification for MEDI-551 was 0.1 μg/mL.	Day 0 (pre-dose)
MEDI-551 Trough Concentration Levels at Day 7	Lower limit of quantification for MEDI-551 was 0.1 μg/mL.	Day 7
MEDI-551 Trough Concentration Levels at Day 28	Lower limit of quantification for MEDI-551 was 0.1 μg/mL.	Day 28
MEDI-551 Trough Concentration Levels at Day 56	Lower limit of quantification for MEDI-551 was 0.1 μg/mL.	Day 56
MEDI-551 Trough Concentration Levels at Day84	Lower limit of quantification for MEDI-551 was 0.1 μg/mL.	Day 84
MEDI-551 Trough Concentration Levels at Day 112	Lower limit of quantification for MEDI-551 was 0.1 μg/mL.	Day 112
MEDI-551 Trough Concentration Levels at Day 140	Lower limit of quantification for MEDI-551 was 0.1 μg/mL.	Day 140
MEDI-551 Trough Concentration Levels at Day 168	Lower limit of quantification for MEDI-551 was 0.1 μg/mL.	Day 168
Anti-MEDI-551 Antibodies	Only 1 patient was tested positive for ADA at pre-dose of Cycle 1 Day 1. However, it was considered as false-positive because the titer value was close to the cut point, and this patient was tested negative for ADA at all subsequent cycles post-baseline.	From baseline to 30 days after the last dose of study drug
Number of Participants With Tumour Response in FL Patients	Tumour response is defined as complete remission (CR) or partial remission (PR) (Cheson BD et al 2007). CR: Nodal Masses: (a) FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative; (b) Variably FDG-avid or PET negative; regression to normal size on CT; Spleen, Liver: Not palpable, nodules disappeared. Bone Marrow: Infiltrate cleared on repeat biopsy; if indeterminate by morphology, immunohistochemistry should be negative. PR: Nodal Masses: ≥50% decrease in sum of the product of the diameters (SPD) of up to 6 largest dominant masses; no increase in size of other nodes; (a) FDG-avid or PET positive prior to therapy; ≥1 PET positive at previously involved site; (b) Variably FDG-avid or PET negative; regression on CT. Spleen, Liver: ≥50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen. Bone Marrow: Irrelevant if positive prior to therapy; cell type should be specified.	From the baseline to 30 days after the last dose of study drug
Number of Participants With Tumour Response in DLBCL Patients	Tumour response is defined as complete remission (CR) or partial remission (PR) (Cheson BD et al 2007). CR: Nodal Masses: (a) FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative; (b) Variably FDG-avid or PET negative; regression to normal size on CT; Spleen, Liver: Not palpable, nodules disappeared. Bone Marrow: Infiltrate cleared on repeat biopsy; if indeterminate by morphology, immunohistochemistry should be negative. PR: Nodal Masses: ≥50% decrease in sum of the product of the diameters (SPD) of up to 6 largest dominant masses; no increase in size of other nodes; (a) FDG-avid or PET positive prior to therapy; ≥1 PET positive at previously involved site; (b) Variably FDG-avid or PET negative; regression on CT. Spleen, Liver: ≥50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen. Bone Marrow: Irrelevant if positive prior to therapy; cell type should be specified.	From the baseline to 30 days after the last dose of study drug
Number of Participants With Tumour Response in CLL Patients	Tumour response is defined as complete remission (CR) or partial remission (PR) (Hallek M et al 2008). CR: all of the following criteria have to be met, and patients have to lack disease-related constitutional symptoms; Lymphadenopathy: None; Hepatomegaly: None; Splenomegaly: None; Blood lymphocytes: <4000/μL; Marrow: Normocellular, <30%lymphocytes, no B-lymphoid nodules, hypocellular marrow defines CR with incomplete marrow recovery; Platelet count: >100000/μL; Hemoglobin: >11.0 g/dL; Neutrophils: >1500/μL PR: at least 2 of the criteria of group A plus 1 of the criteria of group B have to be met. Group A: Lymphadenopathy: Decrease ≥50%; Hepatomegaly: Decrease ≥50%; Splenomegaly: Decrease ≥50%; Blood lymphocytes: Decrease ≥50% from baseline; Marrow: 50% reduction in marrow infiltrate, or B-lymphoid nodules. Group B: Platelet count: 100000/μL or increase ≥50% over baseline; Hemoglobin: >11.0 g/dL or increase ≥50% over baseline; Neutrophils: >1500/μL or >50% improvement over baseline.	From the baseline to 30 days after the last dose of study drug
Number of Participants With Tumour Response in MM Patients	Tumour response is defined as complete response (CR) or partial response (PR) (Durie M et al 2006). CR: Negative immunofixation on the serum and urine, and Disappearance of any soft tissue plasmacytomas and 5% or less plasma cells in bone marrow PR: ≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to <200mg per 24 h. If the serum and urine M-protein are unmeasurable, a ≥50% decrease in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria. If serum and urine M-protein are unmeasurable, and serum free light assay is also unmeasurable, ≥50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cell percentage was ≥30%. In addition to the above listed criteria, if present at baseline, a ≥50% reduction in the size of soft tissue plasmacytomas is also required.	From the baseline to30 days after the last dose of study drug

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: MedImmune LLC

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2011
• Primary Completion (Actual): September 15, 2015
• Study Completion (Actual): September 15, 2015

Study Registration Dates

• First Submitted: October 1, 2013
• First Submitted That Met QC Criteria: October 1, 2013
• First Posted (Estimate): October 8, 2013

Study Record Updates

• Last Update Posted (Actual): June 12, 2017
• Last Update Submitted That Met QC Criteria: May 8, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Japanese; Phase I; CD19; advanced; B cell malignancies; dose escalation
• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms
• Other Study ID Numbers: D2850C00001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No