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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: February 27, 2017
Last verified: February 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: No masking
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

Resource links provided by NLM:


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 Torelable Dose [ Time Frame: From baseline to 28 days after the first dose of study drug ]
  • MEDI-551 Trough Concentration Levels at Day 0 (Pre-dose) [ Time Frame: Day 0 (pre-dose) ]
  • MEDI-551 Trough Concentration Levels at Day 7 [ Time Frame: Day 7 ]
  • MEDI-551 Trough Concentration Levels at Day 28 [ Time Frame: Day 28 ]
  • MEDI-551 Trough Concentration Levels at Day 56 [ Time Frame: Day 56 ]
  • MEDI-551 Trough Concentration Levels at Day84 [ Time Frame: Day 84 ]
  • MEDI-551 Trough Concentration Levels at Day 112 [ Time Frame: Day 112 ]
  • MEDI-551 Trough Concentration Levels at Day 140 [ Time Frame: Day 140 ]
  • MEDI-551 Trough Concentration Levels at Day 168 [ Time Frame: Day 168 ]
  • 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 to30 days after the last dose of study drug ]

    Patients will be assessed by CT scan and physical exam every 2 cycles while on treatment. For patient who stopped treatment with PD, CT scan at 3 months follow up is not needed. FDGPET (or PET-CT) will be performed at Cycle 2, Day 1 only to assess response to MEDI-551 if FDG-avid or variable lesions were noted on screening FDG-PET scan (or PET-CT), and will not be used for staging purposes. BM biopsy will be performed on patients who achieve CR and had a positive BM biopsy at study entry.

    Criteria for CR and partial response (PR) will be according to the International Working Group criteria (Cheson BD et al 2007). CR unconfirmed will not be used to assess response.

    Tumour response is defined as CR or PR


  • Number of Participants With Tumour Response in DLBCL Patients [ Time Frame: From the baseline to30 days after the last dose of study drug ]

    Patients will be assessed by CT scan and physical exam every 2 cycles while on treatment. For patient who stopped treatment with PD, CT scan at 3 months follow up is not needed. FDGPET (or PET-CT) will be performed at Cycle 2, Day 1 only to assess response to MEDI-551 if FDG-avid or variable lesions were noted on screening FDG-PET scan (or PET-CT), and will not be used for staging purposes. BM biopsy will be performed on patients who achieve CR and had a positive BM biopsy at study entry.

    Criteria for CR and partial response (PR) will be according to the International Working Group criteria (Cheson BD et al 2007). CR unconfirmed will not be used to assess response.

    Tumour response is defined as CR or PR


  • Number of Participants With Tumour Response in CLL Patients [ Time Frame: From the baseline to 30 days after the last dose of study drug ]

    Patients will be assessed by haematology and physical exam every cycle. For patients who achieve haematological CR and had evidence of nodal disease by CT scan at screening, a repeat CT scan will be performed. BM biopsy will be performed 3 months following CR to confirm CR. A repeat BM biopsy will be performed 4 weeks later in patients where the initial BM biopsy is considered hypocellular. Patients who do not achieve CR need not have a follow-up BM biopsy.

    Assessment of disease response for CLL will be determined according to the National Cancer Institute - Working Group guidelines on CLL (Hallek M et al 2008).

    Tumour response is defined as CR or PR


  • Number of Participants With Tumour Response in MM Patients [ Time Frame: From the baseline to30 days after the last dose of study drug ]
    Response in MM will be determined using the criteria published by Durie et al (Durie M et al 2006). Evaluations will include assessment of serum and urine paraproteins, assessment of bony lesions by CT or standard radiography (if clinically indicated) and assessment of BM involvement by BM biopsy and/or aspirate. BM biopsy will only be performed to characterize CR in patients who achieve negative serum and urine M-protein by SPEP and UPEP. Blood will be collected for SPEP and 24 hour urine sample will be collected for UPEP and tested at local laboratories.


Enrollment: 32
Study Start Date: May 2011
Study Completion Date: September 2015
Primary Completion Date: September 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
Investigators
Study Director: Trishna Goswami 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: February 27, 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 May 23, 2017