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Safety and Efficacy of Blinatumomab in Subjects With Newly Diagnosed High-risk Diffuse Large B-Cell Lymphoma

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ClinicalTrials.gov Identifier: NCT03023878
Recruitment Status : Active, not recruiting
First Posted : January 18, 2017
Last Update Posted : October 17, 2018
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:
A phase 2, multicenter, open-label, single arm clinical trial in adult subjects with newly diagnosed aggressive high-risk DLBCL.

Condition or disease Intervention/treatment Phase
High-risk Diffuse Large B-Cell Lymphoma Drug: Blinatumomab Drug: Investigator's Choice Chemotherapy Phase 2

Detailed Description:
The safety profile of blinatumomab after frontline R-chemotherapy, consisting of either R-CHOP (14 or 21) or R-DA-EPOCH or R-CHOEP, will be determined. The study will consist of a screening period of up to 14 days, a standard of care (SOC) R-chemotherapy run-in period of approximately 21 weeks, a 12 to 16 week blinatumomab treatment period, a 30-day safety follow-up visit, and a long-term follow-up period that begins after the safety follow-up visit is completed until 1 year from the first dose blinatumomab.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 47 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 20150288 A Phase 2 Open-label Study Investigating the Safety and Efficacy of Blinatumomab After Frontline R-Chemotherapy in Adult Subjects With Newly Diagnosed High-risk Diffuse Large B-Cell Lymphoma (DLBCL)
Actual Study Start Date : March 13, 2017
Estimated Primary Completion Date : April 4, 2019
Estimated Study Completion Date : November 15, 2019


Arm Intervention/treatment
Experimental: Blinatumomab

Blinatumomab is administered as a continuous intravenous (IV) infusion. Cycle 1 is 12 weeks (84 days) in duration with step dosing of 9 µg/day x 7 days, 28 µg/day x 7 days, and 112 µg/day until the end of week 8. This is followed by a 4 week treatment free period.

Optional Cycle 2 of Blinatumomab is 4 weeks in duration (28 days), with step dosing of 9 µg/day x 7 days, 28 µg/day x 7 days, and 112 µg/day x 14 days.

Drug: Blinatumomab
Blinatumomab monotherapy
Other Names:
  • AMG103
  • BlinCyto

Drug: Investigator's Choice Chemotherapy
Investigator's Choice Chemotherapy
Other Name: R-CHOP [14 or 21] or R-DA-EPOCH or R-CHOEP




Primary Outcome Measures :
  1. Overall incidence and severity of treatment-emergent adverse events [ Time Frame: Through study completion for an average of 18 months ]
    Overall incidence and severity of treatment-emergent adverse events occurring during the blinatumomab treatment period graded by investigators according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and characterized as related or unrelated to study drug (blinatumomab)


Secondary Outcome Measures :
  1. Tumor response based on objective response rate. [ Time Frame: Through study completion for an average of 18 months ]
    Objective Response Rate, expressed as the proportion of subjects achieving Complete Response (CR) and partial response (PR).

  2. Duration of response [ Time Frame: Through study completion for an average of 18 months ]
    Duration of response

  3. Complete response rate [ Time Frame: Through study completion for an average of 18 months ]
    Complete response (CR) rate

  4. Progression free survival [ Time Frame: Through study completion for an average of 18 months ]
    Progression free survival (PFS) at 1 year from first dose of blinatumomab

  5. Hematopoietic stem cell transplantation rate [ Time Frame: Through study completion for an average of 18 months ]
    Hematopoietic stem cell transplantation (HSCT) rate

  6. Overall survival [ Time Frame: Through study completion for an average of 18 months ]
    Overall survival (OS) from first dose of blinatumomab

  7. Blinatumomab pharmacokinetic parameters [ Time Frame: Through study completion for an average of 18 months ]
    Blinatumomab pharmacokinetic (PK) parameters


Other Outcome Measures:
  1. Minimal residual disease [ Time Frame: Through study completion for an average of 18 months ]
    Minimal residual disease (MRD) measured by the detection of clonotypic IgH sequences by NGS of cell free CT DNA positivity in plasma at various time points before, during, and after SOC R chemotherapy and blinatumomab treatment

  2. Response rate and duration [ Time Frame: Through study completion for an average of 18 months ]
    Response rates and duration according to COO designation or, c myc and/or Bcl 2/Bcl 6 rearrangement as determined from pretreatment specimens

  3. Pharmacodynamics [ Time Frame: Through study completion for an average of 18 months ]
    Pharmacodynamics, including quantitative and qualitative lymphocyte subsets and cytokine levels in peripheral blood at various time points during blinatumomab treatment

  4. Incidence of anti-blinatumomab antibodies [ Time Frame: Through study completiong for an average of 18 months ]
    Incidence of anti blinatumomab antibodies in the study



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Subject has provided informed consent prior to initiation of any study-specific activities/procedures
  • Age ≥ 18 at time of informed consent
  • Subject must have untreated, histologically proven high-risk DLBCL defined by IPI 3 to 5 and/or Double-hit or higher or double protein expression
  • Eastern Cooperative Oncology Group performance status ≤ 2.
  • Subject meets the criteria per investigator's institution to receive SOC R-chemotherapy (ie, R-CHOP [14 or 21] or R-DA-EPOCH or R-CHOEP) of 6 cycles. Subjects may be enrolled on study prior to cycle 1 or cycle 2 of SOC R-chemotherapy
  • Adequate organ and bone marrow function determined within 14 days prior to enrollment defined as:

    • Hematological: Absolute neutrophil count ≥1x10^9/L; Platelet count ≥75x10^9/L;Hemoglobin ≥8g/dL
    • Renal: Creatinine clearance ≥50mL/min;
    • Hepatic: Aspartate aminotransferase/Alanine aminotransferase <3X upper limit of normal (ULN); Total bilirubin <2X ULN (unless Gilbert's Disease or if liver involvement with lymphoma)
  • Subject must have completed 6 cycles of SOC R-chemotherapy and achieved CR, PR or stable disease by PET/CT performed 3 weeks (± 3 days) after cycle 6 of SOC R-chemotherapy. Subjects with PD are not eligible for treatment with blinatumomab and will end the study.

Exclusion Criteria:

  • Clinically relevant central nervous system pathology requiring treatment 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
  • Subject has active infection requiring systemic therapy
  • Prior anti-CD19 therapies
  • Known infection with HIV or chronic infection with hepatitis B virus or hepatitis C virus
  • History of other malignancy 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 malignancy 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 non-invasive carcinoma or carcinoma in situ
  • Subject has known hypersensitivity to immunoglobulins or any of the products or components to be administered during dosing.
  • Subject likely to not 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.
  • History/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.
  • Females 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.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03023878


Locations
United States, Illinois
Research Site
Chicago, Illinois, United States, 60612
Research Site
Maywood, Illinois, United States, 60153
United States, Louisiana
Research Site
New Orleans, Louisiana, United States, 70112
United States, Maryland
Research Site
Baltimore, Maryland, United States, 21201
United States, New Jersey
Research Site
New Brunswick, New Jersey, United States, 08903
United States, Oklahoma
Research Site
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
Research Site
Portland, Oregon, United States, 97213
United States, South Carolina
Research Site
Greenville, South Carolina, United States, 29607
Canada, Alberta
Research Site
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Ontario
Research Site
Sault Ste. Marie, Ontario, Canada, P6B 0A8
Research Site
Toronto, Ontario, Canada, M5G 2M9
France
Research Site
Créteil Cedex, France, 94010
Research Site
Paris Cedex 10, France, 75475
Germany
Research Site
Dresden, Germany, 01307
Research Site
Ulm, Germany, 89081
Spain
Research Site
Sevilla, Andalucía, Spain, 41013
Research Site
Salamanca, Castilla León, Spain, 37007
Research Site
Barcelona, Cataluña, Spain, 08003
Research Site
L Hospitalet De Llobregat, Cataluña, Spain, 08907
Research Site
Valencia, Comunidad Valenciana, Spain, 46026
Research Site
A coruña, Galicia, Spain, 15006
Research Site
Madrid, Spain, 28007
United Kingdom
Research Site
Bristol, United Kingdom, BS2 8ED
Research Site
Sheffield, United Kingdom, S10 2JF
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen

Additional Information:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT03023878     History of Changes
Other Study ID Numbers: 20150288
2016-002190-35 ( EudraCT Number )
First Posted: January 18, 2017    Key Record Dates
Last Update Posted: October 17, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
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
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
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

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Blinatumomab
Antibodies, Bispecific
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs