Clinical phase 2/3 study to investigate the safety and efficacy of Blinatumomab in subjects with Non Hodgkin Lymphoma that did not respond to previous therapy or that relapsed after initially successful previous therapy

Phase 1

Conditions: Subjects with Relapsed/Refractory Aggressive B-Cell Non-Hodgkin Lymphoma (B-NHL)
MedDRA version: 19.0Level: PTClassification code 10020067Term: High grade B-cell lymphoma Burkitt-like lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 19.0Level: PTClassification code 10036710Term: Primary mediastinal large B-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 19.0Level: PTClassification code 10063908Term: Non-Hodgkin's lymphoma unspecified histology aggressiveSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 19.0Level: PTClassification code 10012818Term: Diffuse large B-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2016-002044-16-ES

Lead Sponsor: Amgen Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 41

Inclusion Criteria

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.
2. Age = 18 at the time of informed consent
3. Biopsy proven aggressive B-NHL, including DLBCL NOS, follicular lymphoma Grade 3B, Primary Mediastinal B-Cell Lymphoma, T-cell rich B-cell lymphoma, or DLBCL that represents transformation of indolent NHL, (including follicular, marginal zone, and lymphoplasmacytoid lymphoma) excluding chronic lymphocytic leukemia or Hodgkin Lymphoma. Subjects with prior indolent lymphoma must have received therapy after a diagnosis of transformation that is appropriate for aggressive histology as described in 4. The following histologies are not eligible:
• Lymphoblastic lymphoma
• Burkitt lymphoma
Any histologies not specifically mentioned must be discussed with the medical monitor.
4. Refractory (no prior CMR) or relapsed (prior CMR) following front line treatment of standard multiagent chemotherapy containing an anthracycline AND an approved anti-CD20 agent. Examples of appropriate therapy include but are not limited to R-CHOP (14 or 21), R-CHOEP, and DA-R-EOCH. For refractory disease, PET positivity should be demonstrated no less than 6 weeks after radiotherapy
5. Biopsy evidence of relapsed disease. For subjects with de novo aggressive B-cell lymphoma and primary refractory disease (ie never achieving CMR), biopsy of persistent disease is preferred but persistent PET positivity (ie Deauville = 4) is acceptable at a minimum. For all subjects that have received radiotherapy for DLBCL, PET should be performed no less than 42 days (6 weeks) after the last dose of radiotherapy. For subjects with transformed disease that has been characterized as refractory, rebiopsy (core or excisional biopsy) with demonstration of persistent aggressive B-NHL is required
6. Received 2 cycles of standard of care platinum-based chemotherapy in the S1 setting and had a response of PMD, NMR, PMR as centrally assessed by PET-CT scan or received at least 1 cycle of S1 chemotherapy and had evidence of PD as centrally assessed
7. Radiographically measurable disease with a clearly demarcated nodal lesion at least 1.5 cm in its largest dimension or a target extranodal lesion at least 1.0 cm in its largest dimension
8. Eastern Cooperative Oncology Group (ECOG) performance status = 2
9. Potentially eligible for HDT and autologous HSCT per institutional standards
10. Laboratory parameters (completed within 14 days prior to enrollment and after the last cycle of S1 chemotherapy):
Hematology:
• Absolute neutrophil count (ANC) = 1.0 x 1000000000/L
• Platelets = 75 x 1000000000/L
Chemistry:
• Creatinine clearance = 50 mL/min (calculated)
•Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 3X upper limit of normal (ULN)
•Total bilirubin (TBL) < 2x ULN (unless Gilbert's disease or if liver involvement with lymphoma)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 166
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 166

Exclusion Criteria

1. CMR following S1 chemotherapy
2. Treatment within 30 days prior to randomization with another investigational device or drug study (ies). Other investigational procedures while participating in this study are excluded
3. Prior anti-CD19-directed therapies
4. Prior HDT with autologous HSCT
5. Prior allogeneic HSCT
6. Presence of clinically relevant central nervous system (CNS) pathology such as epilepsy, paresis, aphasia, stroke, severe brain injury, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, or psychosis
7. Evidence of CNS involvement by NHL
8. 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)
9. History of malignancy other than B-NHL within the past 3 years 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
10. Subject has known sensitivity to immunoglobulins or any of the products or components to be administered during dosing.
11. 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 and investigator’s knowledge.
12. 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.
13. Female subjects who are pregnant or breastfeeding or planning to become pregnant or breastfeed while receiving blinatumomab and for an additional 48 hours after the last dose of blinatumomab. (Females of child bearing potential should only be included after a confirmed menstrual period and a negative highly sensitive urine or serum pregnancy test.)
14. Female subjects of childbearing potential unwilling to use an effective method of contraception while receiving blinatumomab and for an additional 48 hours after the last dose of blinatumomab.
Note: The pregnancy, breastfeeding and contraceptive requirements are specific for 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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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