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A Phase 1b Open-Label Study Investigating the Safety and Pharmacokinetics of Administration of Subcutaneous Blinatumomab for the Treatment of Relapsed/Refractory Indolent Non-Hodgkin's Lymphoma

NCT02961881

Description:

Primary Objective: • To evaluate the safety and tolerability of subcutaneous (SC) blinatumomab dose administrations Secondary Objectives: - To determine pharmacokinetics (PK) with continuous intravenous (cIV) and SC administrations - To estimate the maximum tolerated dose (MTD) tested for blinatumomab administered subcutaneously - To determine the incidence of anti-blinatumomab antibody formation following SC administration - To evaluate efficacy response following treatment with SC blinatumomab administration Exploratory Objective: - To determine the pharmacodynamics (PD) time profiles for B-and T-lymphocytes as well as cytokine profiles during SC administration - To evaluate efficacy response following treatment with SC blinatumomab administration using Lugano criteria if positron emission tomography-computed tomography (PET/CT) is used for evaluation

Related Conditions:
  • Follicular Lymphoma
  • Lymphoplasmacytic Lymphoma
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
  • Small Lymphocytic Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1b Open-Label Study Investigating the Safety and Pharmacokinetics of Administration of Subcutaneous Blinatumomab for the Treatment of Relapsed/Refractory Indolent Non-Hodgkin's Lymphoma
  • Official Title: A Phase 1b Open-Label Study Investigating the Safety and Pharmacokinetics of Administration of Subcutaneous Blinatumomab for the Treatment of Relapsed/Refractory Indolent Non-Hodgkin's Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 20140286
  • NCT ID: NCT02961881

Conditions

  • Non-Hodgkin's Lymphoma

Interventions

DrugSynonymsArms
blinatumomabblinatumomab

Purpose

Primary Objective: • To evaluate the safety and tolerability of subcutaneous (SC) blinatumomab dose administrations Secondary Objectives: - To determine pharmacokinetics (PK) with continuous intravenous (cIV) and SC administrations - To estimate the maximum tolerated dose (MTD) tested for blinatumomab administered subcutaneously - To determine the incidence of anti-blinatumomab antibody formation following SC administration - To evaluate efficacy response following treatment with SC blinatumomab administration Exploratory Objective: - To determine the pharmacodynamics (PD) time profiles for B-and T-lymphocytes as well as cytokine profiles during SC administration - To evaluate efficacy response following treatment with SC blinatumomab administration using Lugano criteria if positron emission tomography-computed tomography (PET/CT) is used for evaluation

Trial Arms

NameTypeDescriptionInterventions
blinatumomabExperimental
  • blinatumomab

Eligibility Criteria

        Inclusion Criteria:

          -  Subject or subject's legally acceptable representative has provided informed consent.

          -  Age greater than or equal to 18 years old at the time of informed consent

          -  Subjects must have a histologically determined B cell NHL subtype as defined in the
             bullets below. In addition, they must have disease that is primary refractory after
             initial therapy or have relapsed disease.

          -  Follicular Lymphoma I, II, IIIA

          -  Marginal zone lymphoma (extranodal, nodal or splenic). Subjects with gastric
             mucosa-associated lymphoid tissue must have progressed after Helicobacter pylori
             therapy and radiation. Subjects with splenic marginal zone lymphoma must have prior
             splenectomy.

          -  Lymphoplasmocytic lymphoma

          -  Mantle cell lymphoma ([MCL] with the exception of aggressive MCL, defined as Ki67 >
             30%, or blastoid histology)

          -  Small lymphocytic lymphoma

          -  Disease status must be 1 of the following:

          -  Primary refractory (at least 1 prior line of therapy)

          -  Relapsed within 1 year of first response

          -  Responded to initial therapy for ≥ 1 year and relapsed after 2 or more lines of
             therapy, including an anti-CD20 monoclonal antibody

          -  At least 1 prior line of therapy if primary refractory or relapsed within 1 year.
             Subjects who respond to initial therapy for greater than or equal to 1 year must have
             had at least 2 prior lines of therapy including an anti-CD20 monoclonal antibody.

          -  Measurable disease that has not been previously irradiated on positron emission
             tomography-computed tomography (PET-CT), or computed tomography (CT), of at least 1.5
             cm within the last 21 days before the start of IP treatment.

          -  Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
             (Appendix D).

          -  Life expectancy greater than or equal to 3 months as determined by treating physician.

          -  Subjects must have adequate organ and marrow at screening as defined below:

               -  Platelets greater than or equal to 50,000 mcL

               -  Total bilirubin less than or equal to 1.5 x upper limit of normal (ULN)

               -  Creatinine clearance greater than or equal to 50 mL/min (Cockcroft-Gault)

        Exclusion Criteria:

          -  Currently receiving treatment in another investigational device or drug study, or less
             than 30 days between ending treatment on another investigational device or drug
             study(ies) and start of IP treatment. Other investigational procedures while
             participating in this study are excluded.

          -  Known hypersensitivity to immunoglobulins or any other component of the study drug

          -  Subject likely to not be available to complete all protocol required study visits or
             procedures to the best of the subject and investigator's knowledge

          -  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.

          -  Subjects who have had treatments with anti-cancer agents including rituximab or
             obinutuzumab and/or other monoclonal antibody or radioimmunotherapy within 6 weeks
             before the starting IP treatment.

          -  Autologous stem cell transplantation within 12 weeks before the starting IP treatment
             or past history of allogeneic stem cell transplantation.

          -  Subjects who have received anti-CD 19 targeted therapies, chimeric antigen receptor
             T-cell or other cellular therapies for the treatment of their lymphoma .

          -  Subjects with suspected or known brain metastases should be excluded from this
             clinical study because of their poor prognosis and because they often develop
             progressive neurologic dysfunction that would confound the evaluation of neurologic
             and other adverse events.

          -  Infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis
             B virus or hepatitis C virus.

          -  History of or current relevant central nervous system pathology such as epilepsy,
             recurrent seizures, paresis, aphasia, apoplexia, severe brain injuries, cerebellar
             disease, organic brain syndrome or psychosis.

          -  History of malignancy other than their lymphoma with the exception of:

               -  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.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or
             uncontrolled systemic fungal bacteria, viral, or other infection, symptomatic
             congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric
             illness/social situations that would limit compliance with study requirements.

          -  A female who is pregnant or breastfeeding or planning to become pregnant or breastfeed
             during treatment and for an additional 48 hours (Period 1) or 96 hours (Period 2),
             respectively, after the last dose of blinatumomab (Female subjects of childbearing
             potential should only be included in the study after a confirmed menstrual period and
             a negative highly sensitive urine or serum pregnancy test).

          -  A female of childbearing potential unwilling to use highly effective method of
             contraception during treatment and for an additional 48 hours (Period 1) or 96 hours
             (Period 2), respectively, after the last dose of blinatumomab.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Subject grade of dose limiting toxicities (DLTs)
Time Frame:37 months
Safety Issue:
Description:Subject grade of dose limiting toxicities is the occurrence of any of the toxicities during the DLT evaluation period if judged by the investigator to be related to the administration of blinatumomab.

Secondary Outcome Measures

Measure:Blinatumomab PK parameters (clearance of blinatumomab) under cIV
Time Frame:37 months
Safety Issue:
Description:
Measure:Blinatumomab PK parameters (volume of distribution of blinatumomab) under cIV
Time Frame:37 months
Safety Issue:
Description:
Measure:Blinatumomab PK parameters (clearance of blinatumomab) under SC administrations
Time Frame:37 months
Safety Issue:
Description:
Measure:Blinatumomab PK parameters (volume of distribution of blinatumomab) under SC administrations
Time Frame:37 months
Safety Issue:
Description:
Measure:Maximum Tolerated Dose
Time Frame:37 months
Safety Issue:
Description:
Measure:Incidence of anti-blinatumomab antibodies
Time Frame:37 months
Safety Issue:
Description:
Measure:Overall Response Rate (ORR)
Time Frame:37 months
Safety Issue:
Description:
Measure:Complete Response (CR)
Time Frame:37 months
Safety Issue:
Description:
Measure:Partial Response (PR) as determined by best overall response (ORR) using Cheson criteria
Time Frame:37 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Amgen

Last Updated

December 18, 2019