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History of Changes for Study: NCT03298412
Effect of Blinatumomab on MRD in DLBCL Subjects Post aHSCT
Latest version (submitted September 10, 2020) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 September 26, 2017 None (earliest Version on record)
2 November 16, 2017 Study Status
3 February 19, 2018 Study Status and Contacts/Locations
4 March 5, 2018 Study Status and Contacts/Locations
5 April 3, 2018 Study Status and Contacts/Locations
6 June 4, 2018 Recruitment Status, Study Status and Contacts/Locations
7 June 13, 2018 Study Status and Contacts/Locations
8 June 27, 2018 Contacts/Locations and Study Status
9 July 25, 2018 Study Status and Contacts/Locations
10 August 1, 2018 Study Status and Contacts/Locations
11 August 8, 2018 Contacts/Locations and Study Status
12 August 15, 2018 Contacts/Locations and Study Status
13 August 29, 2018 Contacts/Locations and Study Status
14 September 12, 2018 Study Status and Contacts/Locations
15 October 3, 2018 Study Status and Contacts/Locations
16 October 24, 2018 IPDSharing, Study Description, Contacts/Locations, Eligibility, Outcome Measures, Oversight and Study Status
17 November 7, 2018 Study Status and Contacts/Locations
18 February 15, 2019 Study Status
19 March 20, 2019 Study Status and Contacts/Locations
20 May 29, 2019 Study Status and Contacts/Locations
21 September 13, 2019 Recruitment Status, Study Status and Contacts/Locations
22 October 4, 2019 Recruitment Status, Study Status and Study Design
23 October 11, 2019 Recruitment Status and Study Status
24 August 20, 2020
Quality Control Review has not concluded Returned: September 2, 2020
Outcome Measures, Study Status, Arms and Interventions, Document Section, Eligibility, Study Description and Study Identification
25 September 10, 2020 Study Status, Adverse Events
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Study NCT03298412
Submitted Date:  September 26, 2017 (v1)

Open or close this module Study Identification
Unique Protocol ID: 20150291
Brief Title: Effect of Blinatumomab on MRD in DLBCL Subjects Post aHSCT
Official Title: A Phase 2 Open-Label Study to Determine the Effect of Blinatumomab on Minimal Residual Disease in Subjects With High-risk Diffuse Large B-cell Lymphoma Post-autologous Hematopoietic Stem-cell Transplantation.
Secondary IDs: 2016-003255-30 [EudraCT Number]
Open or close this module Study Status
Record Verification: September 2017
Overall Status: Not yet recruiting
Study Start: February 5, 2018
Primary Completion: May 14, 2020 [Anticipated]
Study Completion: February 5, 2021 [Anticipated]
First Submitted: September 12, 2017
First Submitted that
Met QC Criteria:
September 26, 2017
First Posted: October 2, 2017 [Actual]
Last Update Submitted that
Met QC Criteria:
September 26, 2017
Last Update Posted: October 2, 2017 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Amgen
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: The study will estimate the minimal residual disease (MRD)-negative response rate after treatment with blinatumomab in subjects with high-risk DLBCL who are MRD-positive following aHSCT. The clinical hypothesis is that the MRD-negative response rate will be > 10%. Achieving an MRD-negative response rate of 30% would be of scientific and clinical interest.
Detailed Description: This is a phase 2, multicenter, open-label, single arm estimation study in adult subjects with high-risk DLBCL in complete remission. The study will consist of up to a 21-day screening period, a run-in period of up to 24 months, a 12-week treatment period (8 weeks of blinatumomab treatment followed by a 4-week treatment free period), a 30-day safety follow-up visit after the last dose of blinatumomab, and a long-term follow-up period that begins after the safety follow-up visit is completed until 1 year from the first dose of blinatumomab. The study will enroll approximately 90 subjects in the screening period with biopsy proven, high-risk DLBCL that are positron emission tomography-computer tomography (PET-CT) negative 90 days (± 30 days) post aHSCT. During the run-in period subjects will be followed by clinic visits at regular interval for up to 24 months for monitoring of MRD status in plasma by a next generation sequencing (NGS)-based assay. It is estimated 30 subjects will be either MRD-positive at screening or become MRD-positive during the 24-month run-in period. The number of subjects enrolled may be altered in order to ensure that approximately 30 subjects are assigned to treatment with blinatumomab. Enrollment may be stopped, once approximately 30 subjects have been assigned to treatment with blinatumomab.
Open or close this module Conditions
Conditions: High-risk Diffuse Large B-cell Lymphoma
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Single Group Assignment
Number of Arms: 1
Masking: None (Open Label)
Allocation: N/A
Enrollment: 90 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Blinatumomab
Blinatumomab is administered as a continuous intravenous (IV) infusion.
Drug: Blinatumomab

Blinatumomab will be supplied as 4 mL single-use sterile glass injection vials. Blinatumomab is administered as a continuous intravenous (IV) infusion.

Cycle 1 of blinatumomab treatment is 12 weeks (84 days) in duration and includes 8 weeks (56 days) of blinatumomab IV infusion followed by a 4-week (28-day) treatment-free interval. The initial dose of blinatumomab will be 9 μg/day for the first 7 days of treatment. Blinatumomab dose will then be escalated (dose-step) to 28 μg/day starting on day 8 (week 2) followed by a dose-step to 112 μg/day starting on day 15 (week 3) and continuing until completion of therapy (day 57 of cycle 1).

Open or close this module Outcome Measures
Primary Outcome Measures:
1. Minimal residual disease
[ Time Frame: Cycle 1 is 12 weeks (84 days) in duration and includes 8 weeks (56 days) of blinatumomab IV infusion followed by a 4-week (28-day) treatment-free interval (day 57 to 84). ]

To determine minimal residual disease (MRD) negative rate following blinatumomab treatment in high-risk Diffuse Large B-cell Lymphoma (DLBCL) subjects who are MRD-positive post-autologous hematopoietic stem cell transplantation (aHSCT).
Secondary Outcome Measures:
1. Progression-free survival
[ Time Frame: Cycle 1 is 12 weeks (84 days) in duration and includes 8 weeks (56 days) of blinatumomab IV infusion followed by a 4-week (28-day) treatment-free interval (day 57 to 84). ]

To describe the efficacy of blinatumomab in relation to progression-free survival
2. Duration of MRD-negative status
[ Time Frame: Run in part 1 to determine MRD status can last up to 24 months ]

To describe the efficacy of blinatumomab in relation to MRD-negative status
3. Overall Survival
[ Time Frame: Visits occur every 3 months for maximum of 1 year after Cycle 1, or until relapse ]

To describe the efficacy of blinatumomab in relation to overall survival
4. Adverse Events
[ Time Frame: Cycle 1 is 12 weeks (84 days) in duration and includes 8 weeks (56 days) of blinatumomab IV infusion followed by a 4-week (28-day) treatment-free interval (day 57 to 84). ]

Incidence, grade and severity of treatment emergent adverse events
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 100 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion and Exclusion Criteria - Part 1 Inclusion Criteria - Part 1

• Subject has provided informed consent prior to initiation of any study-specific activities/procedures or subject's legally acceptable representative has provided informed consent prior to any study-specific activities/procedures being initiated when the subject has any kind of condition that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent.

  • Age ≥ 18 at time of informed consent
  • Biopsy-proven DLBCL excluding DLBCL that represents transformation of indolent NHL Note: Lymphoblastic Lymphoma and Burkitt Lymphoma histology are not eligible
  • Subject has ≥ 1 characteristic feature of high-risk DLBCL:

    o High-risk first complete remission (defined as interim PET-CT positive or < complete remission to frontline chemotherapy AND achieved complete remission to platinum-containing salvage)

    o Relapse within 1 year of diagnosis

    • Secondary aaIPI > 1 (see Appendix D)
    • Partial response/partial metabolic response after minimum of 2 cycles of
    • platinum-containing salvage chemotherapy
    • C-myc rearrangement
  • aHSCT with high-dose chemotherapy following first (or later) salvage treatment.
  • PET-CT negative (Deauville score ≤ 3) 90 days (± 30 days) post aHSCT
  • Available relapsed and/or diagnostic pathology formalin-fixed paraffin-embedded (FFPE) tumor block or slide samples at the time of enrollment including the successful identification of malignant clone sequences by the central laboratory.
  • MRD plasma sample collected ≤ 3 weeks from post aHSCT PET-CT scan
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  • Adequate organ function determined ≤ 3 weeks prior to enrollment defined as follows:

    o Hematological: Absolute neutrophil count (ANC) ≥ 1.0 x 109/L Platelet count ≥ 75 x 109/L Hemoglobin ≥ 8 g/dL

    o Renal: Creatinine clearance ≥ 50 mL/min Cockcroft-Gault equation

    o Hepatic: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN) Total bilirubin < 2 x ULN (unless Gilbert's Disease or if liver involvement with lymphoma)

  • Subject will be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject's and investigator's knowledge including but not limited to:
  • Completion of up to a 24-month run-in period
  • Completion of all regularly scheduled study visits including blood draws for
  • MRD assessment, clinical disease state assessment, PET-CT scans (ie, at time of MRD positivity or relapse), assignment to treatment with blinatumomab

Other Inclusion Criteria may apply

Exclusion Criteria - Part 1

• Clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia,stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, and psychosis

  • Evidence of CNS involvement with DLBCL
  • Current autoimmune disease or history of autoimmune disease with potential of CNS involvement
  • Prior anti-CD19 directed therapies
  • Prior alloHSCT
  • Received radiation ≤ 2 weeks prior to enrollment
  • Known infection with human immunodeficiency virus or chronic infection with hepatitis B virus (hepatitis B surface antigen positive) or hepatitis C virus (anti-hepatitis C virus positive)
  • History of malignancy other than DLBCL within the past 3 years with the following exceptions:

    o Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before enrollment and felt to be at low risk for recurrence by the treating physician

    o Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease

    o Adequately treated cervical carcinoma in situ without evidence of disease

    • Adequately treated breast ductal carcinoma in situ without evidence of disease
    • Prostatic intraepithelial neoplasia without evidence of prostate cancer
    • Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ
  • Subject has known hypersensitivity to immunoglobulins or any of the products or components to be administered during dosing.
  • History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
  • Women who are pregnant or breastfeeding or planning to become pregnant or breastfeed while receiving blinatumomab and for an additional 48 hours after the last treatment dose of blinatumomab. (Females of child bearing potential should only be included after a negative highly sensitive urine or serum pregnancy test.)
  • Women of childbearing potential unwilling to use an acceptable method of effective contraception while receiving blinatumomab and for an additional 48 hours after last dose of blinatumomab. Note: The pregnancy, breastfeeding and contraceptive requirements are specific to blinatumomab. The investigator is responsible for providing the subject (male and female) with pregnancy and breastfeeding (female only) avoidance requirements for other medications given during the study.
  • Currently receiving treatment in another investigational device or drug study or less than 30 days since ending treatment on another investigational device or drug study. Other investigational procedures while participating in this study are excluded.

Inclusion and Exclusion Criteria - Part 2 Inclusion Criteria - Part 2

  • MRD-positive assessment (by NGS analysis) at enrollment or at any time during the run-in 1 period
  • PET-CT negative (defined by Deauville criteria ≤ 3) at run-in 2 performed ≤ 3 weeks from MRD-positive assessment at run-in 1. Historical PET-CT are allowed if performed ≤ 6 weeks from day 1 (first dose of blinatumomab) and subject has no clinical signs or symptoms suggestive of disease progression (eg, increase in lactate dehydrogenase [LDH] not otherwise explained)
  • Adequate organ function determined ≤ 2 week prior to treatment assignment with blinatumomab as follows:
    • Hematological:

ANC ≥ 1.0 x 109/L Hemoglobin ≥ 8 g/L Platelet count ≥ 75 x 109/L o Renal: Creatinine clearance ≥ 50 mL/min Cockcroft-Gault equation

o Hepatic: AST and ALT < 3 x ULN Total bilirubin < 2 x ULN (unless Gilbert's Disease or if liver involvement with lymphoma)

Exclusion Criteria - Part 2 Subject has active infection requiring systemic therapy Any change in the part 1 eligibility criteria during the run-in period.

Other Exclusion Criteria may apply

Open or close this module Contacts/Locations
Central Contact Person: Amgen Call Center
Telephone: 866-572-6436
Email: medinfo@amgen.com
Study Officials: MD
Study Director
Amgen
Locations:
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Citations:
Links: Description: AmgenTrials clinical trials website
Available IPD/Information:

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