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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

This study has been completed.
Sponsor:
Collaborator:
MedImmune LLC
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01957579
First received: October 1, 2013
Last updated: May 8, 2017
Last verified: May 2017
  Purpose
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.

Condition Intervention Phase
Blood Cancer Advanced B Cell Malignancies Drug: MEDI-551 Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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

Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Number of Participants With Adverse Events [ Time Frame: From baseline to 30 days after the last dose of study drug ]

Secondary Outcome Measures:
  • 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.



Enrollment: 32
Actual Study Start Date: May 25, 2011
Study Completion Date: September 15, 2015
Primary Completion Date: September 15, 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   20 Years to 130 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01957579

Locations
Japan
Research Site
Fukuoka-shi, Japan
Research Site
Isehara-shi, Japan
Research Site
Nagoya-shi, Japan
Sponsors and Collaborators
AstraZeneca
MedImmune LLC
  More Information

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01957579     History of Changes
Obsolete Identifiers: NCT01377116
Other Study ID Numbers: D2850C00001
Study First Received: October 1, 2013
Results First Received: February 27, 2017
Last Updated: May 8, 2017

Keywords provided by AstraZeneca:
Phase I
advanced
B cell malignancies
dose escalation
CD19
Japanese

Additional relevant MeSH terms:
Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Hematologic Diseases

ClinicalTrials.gov processed this record on August 21, 2017