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

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ClinicalTrials.gov Identifier: NCT01957579
Recruitment Status : Completed
First Posted : October 8, 2013
Results First Posted : April 10, 2017
Last Update Posted : June 12, 2017
Sponsor:
Collaborator:
MedImmune LLC
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE October 1, 2013
First Posted Date  ICMJE October 8, 2013
Results First Submitted Date February 27, 2017
Results First Posted Date April 10, 2017
Last Update Posted Date June 12, 2017
Actual Study Start Date  ICMJE May 25, 2011
Actual Primary Completion Date September 15, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 27, 2017)
Number of Participants With Adverse Events [ Time Frame: From baseline to 30 days after the last dose of study drug ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 1, 2013)
  • Number of Patients with Adverse Events [ Time Frame: From baseline to 30 days after the last dose of study drug ]
  • Change from Baseline to 30days after the last ndose of MEDI-551 in laboratory data, vital signs, and ECG [ Time Frame: From baseline to 30 days after the last dose of study drug ]
Change History Complete list of historical versions of study NCT01957579 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 8, 2017)
  • Number of Participants With Dose Limiting Toxicities [ Time Frame: From baseline to 28 days after the first dose of study drug ]
    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.
  • Maximum Tolerated Dose [ Time Frame: From baseline to 28 days after the first dose of study drug ]
    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.
  • MEDI-551 Trough Concentration Levels at Day 0 (Pre-dose) [ Time Frame: Day 0 (pre-dose) ]
    Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
  • MEDI-551 Trough Concentration Levels at Day 7 [ Time Frame: Day 7 ]
    Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
  • MEDI-551 Trough Concentration Levels at Day 28 [ Time Frame: Day 28 ]
    Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
  • MEDI-551 Trough Concentration Levels at Day 56 [ Time Frame: Day 56 ]
    Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
  • MEDI-551 Trough Concentration Levels at Day84 [ Time Frame: Day 84 ]
    Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
  • MEDI-551 Trough Concentration Levels at Day 112 [ Time Frame: Day 112 ]
    Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
  • MEDI-551 Trough Concentration Levels at Day 140 [ Time Frame: Day 140 ]
    Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
  • MEDI-551 Trough Concentration Levels at Day 168 [ Time Frame: Day 168 ]
    Lower limit of quantification for MEDI-551 was 0.1 μg/mL.
  • Anti-MEDI-551 Antibodies [ Time Frame: From baseline to 30 days after the last dose of study drug ]
    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.
  • Number of Participants With Tumour Response in FL Patients [ Time Frame: From the baseline to 30 days after the last dose of study drug ]
    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.
  • Number of Participants With Tumour Response in DLBCL Patients [ Time Frame: From the baseline to 30 days after the last dose of study drug ]
    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.
  • Number of Participants With Tumour Response in CLL Patients [ Time Frame: From the baseline to 30 days after the last dose of study drug ]
    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.
  • Number of Participants With Tumour Response in MM Patients [ Time Frame: From the baseline to30 days after the last dose of study drug ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 1, 2013)
  • To characterize the drug concentrations in serum and effect on circulating lymphocyte populations and Ig levels [ Time Frame: From baseline to 3 months after the last dose of study drug ]
  • Immunogenicity of MEDI-551 by measuring anti-MEDI-551 antibodies [ Time Frame: From baseline to 3 months after the last dose of study drug ]
  • Anti-tumor activity of MEDI-551 using Complete Response Rate [ Time Frame: From the baseline to30 days after the last dose of study drug ]
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 1, Dose-escalation Study of MEDI-551 in Japanese Adult Patients With Relapsed or Refractory Advanced B-cell Malignancies
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Blood Cancer
  • Advanced B Cell Malignancies
Intervention  ICMJE 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
Study Arms Experimental: MEDI-551
Intervention: Drug: MEDI-551
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 4, 2015)
32
Original Estimated Enrollment  ICMJE
 (submitted: October 1, 2013)
16
Actual Study Completion Date September 15, 2015
Actual Primary Completion Date September 15, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender
Sexes Eligible for Study: All
Ages 20 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01957579
Other Study ID Numbers  ICMJE D2850C00001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE MedImmune LLC
Investigators  ICMJE Not Provided
PRS Account AstraZeneca
Verification Date May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP