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Trial record 1 of 1 for:    NCT03298412 | France
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Effect of Blinatumomab on Minimal Residual Disease (MRD) in Diffuse Large B-Cell Lymphoma (DLBCL) Subjects Post Autologous Hematopoietic Stem Cell Transplantation (aHSCT)

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ClinicalTrials.gov Identifier: NCT03298412
Recruitment Status : Terminated (Early Closure due to rare patient population)
First Posted : October 2, 2017
Results First Posted : September 11, 2020
Last Update Posted : September 11, 2020
Sponsor:
Information provided by (Responsible Party):
Amgen

Tracking Information
First Submitted Date  ICMJE September 12, 2017
First Posted Date  ICMJE October 2, 2017
Results First Submitted Date  ICMJE August 20, 2020
Results First Posted Date  ICMJE September 11, 2020
Last Update Posted Date September 11, 2020
Actual Study Start Date  ICMJE May 23, 2018
Actual Primary Completion Date September 30, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 20, 2020)
MRD-Negative Rate at the End of Cycle 1 [ Time Frame: 12 weeks (84 days) ]
The estimated MRD-negative rate, calculated as the percentage of participants with MRD-negative status after treatment with blinatumomab. MRD-negative status was assessed by positron emission tomography-computed tomography (PET-CT) or computed tomography (CT).
Original Primary Outcome Measures  ICMJE
 (submitted: September 26, 2017)
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).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 20, 2020)
  • Kaplan-Meier Estimate: Progression-Free Survival (PFS) [ Time Frame: up to 1 year from first dose of blinatumomab ]
    PFS, calculated as the time from the date of first dose of blinatumomab until the date of diagnosis of relapse of lymphoma (by PET-CT, CT, clinical assessment or relapse biopsy, whichever was the preferred method), or date of death, whichever was earliest. Participants who were alive and who did not have progression or new anti-tumor treatment (excluding any stem cell transplantation) were to be censored at last date of tumor assessment.
  • Kaplan-Meier Estimate: Duration of MRD-Negative Status [ Time Frame: up to 1 year from first dose of blinatumomab ]
    The duration of MRD-negative status, assessed only in participants who achieve MRD-negative status after blinatumomab treatment, was defined as the time when a negative MRD result was first established until documented MRD-positive re-occurrence, disease progression or, death due to any cause. Participants without any of these events at the time of the analysis were to be censored at their last disease assessment date. MRD-negative status was assessed by PET-CT or CT.
  • Kaplan-Meier Estimate: Overall Survival (OS) [ Time Frame: up to 1 year from first dose of blinatumomab ]
    OS, defined as time from the first dose of blinatumomab treatment until death due to any cause. Participants still alive at the time of the analysis were censored at date last known to be alive.
  • Number of Participants With Treatment Emergent Adverse Events (TEAEs) [ Time Frame: From first dose of study drug through 30 days after the last dose of study drug. The treatment duration for the participant who received blinatumomab was 57 days. ]
    An adverse event (AE) is defined as any untoward medical occurrence. A serious AE is defined as an AE that is: fatal; life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; a congenital anomaly/birth defect; other medically important serious event. TEAEs are events with an onset after the administration of the first dose of blinatumomab treatment through 30 days after the end of blinatumomab treatment. Events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE): Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), Grade 5 (death).
Original Secondary Outcome Measures  ICMJE
 (submitted: September 26, 2017)
  • 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
  • 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
  • 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
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of Blinatumomab on Minimal Residual Disease (MRD) in Diffuse Large B-Cell Lymphoma (DLBCL) Subjects Post Autologous Hematopoietic Stem Cell Transplantation (aHSCT)
Official Title  ICMJE 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.
Brief Summary The study will estimate the 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 greater than 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 28-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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE High-risk Diffuse Large B-cell Lymphoma
Intervention  ICMJE Drug: Blinatumomab
Blinatumomab is administered as a continuous IV infusion.
Other Names:
  • BLINCYTO
  • AMG 103
Study Arms  ICMJE Experimental: Blinatumomab

After a run-in period of up to 24 months to evaluate MRD status and assess eligibility for treatment assignment, participants received blinatumomab intravenous (IV) infusion at an initial dose of 9 μg/day for the first 7 days of treatment, 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).

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.

Intervention: Drug: Blinatumomab
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 Terminated
Actual Enrollment  ICMJE
 (submitted: October 4, 2019)
10
Original Estimated Enrollment  ICMJE
 (submitted: September 26, 2017)
90
Actual Study Completion Date  ICMJE September 30, 2019
Actual Primary Completion Date September 30, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 non-Hodgkin's lymphoma (NHL) Note: Lymphoblastic Lymphoma and Burkitt Lymphoma histology are not eligible
  • Subject has ≥ 1 characteristic feature of high-risk DLBCL:

    • High-risk first complete remission (defined as interim positron emission tomography - computed tomography (PET-CT) positive or < complete remission to frontline chemotherapy AND achieved complete remission to platinum-containing salvage)
    • Relapse within 1 year of diagnosis
    • Secondary age-adjusted international prognostic index > 1
    • 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 after the 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:

    • Hematological:

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

  • Renal:

Creatinine clearance ≥ 50 mL/min Cockcroft-Gault equation

  • 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. See "Inclusion and Exclusion criteria - Part 2".

Exclusion Criteria - Part 1

  • Clinically relevant central nervous system (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 at disease evaluation obtained prior to starting blinatumomab
  • 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
  • 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:

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

    • Other Exclusion criteria may apply. See "Inclusion and Exclusion criteria - Part 2".

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 test result available to the site 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 ≤ 7 days 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

  • Renal:

Creatinine clearance ≥ 50 mL/min Cockcroft-Gault equation

  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Australia,   Belgium,   Greece,   Italy,   Switzerland,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03298412
Other Study ID Numbers  ICMJE 20150291
2016-003255-30 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
URL: https://www.amgen.com/datasharing
Current Responsible Party Amgen
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Amgen
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: MD Amgen
PRS Account Amgen
Verification Date September 2020

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