Clinical trial NCT03023878: Safety and Efficacy of Blinatumomab in Adults With Newly Diagnosed High-risk Diffuse Large B-Cell Lymphoma
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: High-risk Diffuse Large B-Cell Lymphoma
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2017-01-18
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed description: The safety profile of blinatumomab after frontline rituximab (R)-chemotherapy, consisting of either R-CHOP (14 or 21) (rituximab/cyclophosphamide/doxorubicin/vincristine/prednisone) or R-DA-EPOCH (rituximab and dose adjusted-etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin), or R-CHOEP (rituximab and cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide), 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.

Eligibility 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 atleast one of the following:

  * International Prognostic Index (IPI) for Diffuse Large B-cell Lymphoma 3 to 5 (representing high intermedidate - high ratings),
  * 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 standard of care (SOC) rituximab-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 ≥1\*10\^9/L; Platelet count ≥75\*10\^9/L;Hemoglobin ≥8g/dL
  * Renal: Creatinine clearance ≥50mL/min;
  * Hepatic: Aspartate aminotransferase/Alanine aminotransferase \<3\*upper limit of normal (ULN); Total bilirubin \<2\*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 progressive disease (PD) are not eligible for treatment with blinatumomab and will end the study.

Exclusion Criteria:

* Clinically relevant central nervous system (CNS) 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.

Primary outcomes:
measure: Participants With Treatment-Emergent (Blinatumomab) Adverse Events
timeFrame: From the start of first infusion of IP to 30 days after the end of last infusion of IP; median (min, max) treatment duration was 56 (16, 84) days
measure: Participants With Treatment-Emergent Adverse Events Related to Blinatumomab Treatment
timeFrame: From the start of first infusion of IP to 30 days after the end of last infusion of IP; median (min, max) treatment duration was 56 (16, 84) days
Secondary outcomes:
measure: Overall Objective Response Rate (ORR) Expressed as the Percentage of Participants Achieving Complete Metabolic Response (CMR) and Partial Metabolic Response (PMR) Using Lugano 2014 Criteria During Cycle 1 and During Treatment Period
timeFrame: Cycle 1: Day 78 (3 weeks following end of Cycle 1 IP treatment) Treatment Period: Either the Cycle 1 timeframe or approximately Day 128 (3 weeks after Cycle 2 ended) for participants who completed Cycle 2
measure: Kaplan-Meier Estimates for Duration of Response
timeFrame: The median (range) follow-up time was 11.5 (8.2, 14.5) months
measure: Complete Response Rate Expressed as the Percentage of Participants Achieving Complete Metabolic Response (CMR) Using Lugano 2014 Criteria During Cycle 1 and During Treatment Period
timeFrame: Cycle 1: Day 78 (3 weeks following end of Cycle 1 IP treatment) Treatment Period: Either the Cycle 1 timeframe or approximately Day 128 (3 weeks after Cycle 2 ended) for participants who completed Cycle 2
measure: Kaplan-Meier Estimates for Overall Survival (OS) From First Dose of Blinatumomab
timeFrame: The median (range) follow-up time was 12.0 (10.7, 14.5) months.
measure: Kaplan-Meier Estimates for Progression Free Survival (PFS) From First Dose of Blinatumomab
timeFrame: The median (range) follow-up time was 12.0 (8.2, 14.5)
measure: Percentage of Participants Who Had Hematopoietic Stem Cell Transplantation (HSCT)
timeFrame: Day 1 up to 14.5 months
measure: Pharmacokinetics (PK) Results for Blinatumomab: Steady-State Concentrations at Week 1, Week 2 and Week 3 for Cycle 1
timeFrame: Day 2 at least 24 hours after blinatumomab was started and on Day 9 and Day 16 at least 24 hours after blinatumomab dose was increased in the cycle
measure: Pharmacokinetics (PK) Results for Blinatumomab: Clearance for Cycle 1
timeFrame: Day 2 at least 24 hours after blinatumomab was started and on Day 9 and Day 16 at least 24 hours after blinatumomab dose was increased in the cycle
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Maywood
country: United States
facility: Research Site
state: Illinois
city: New Orleans
country: United States
facility: Research Site
state: Louisiana
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: New Brunswick
country: United States
facility: Research Site
state: New Jersey
city: Oklahoma City
country: United States
facility: Research Site
state: Oklahoma
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Greenville
country: United States
facility: Research Site
state: South Carolina
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Sault Ste. Marie
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Créteil Cedex
country: France
facility: Research Site
city: Paris Cedex 10
country: France
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Ulm
country: Germany
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
state: Andalucía
city: Salamanca
country: Spain
facility: Research Site
state: Castilla León
city: Barcelona
country: Spain
facility: Research Site
state: Cataluña
city: L Hospitalet De Llobregat
country: Spain
facility: Research Site
state: Cataluña
city: Valencia
country: Spain
facility: Research Site
state: Comunidad Valenciana
city: A coruña
country: Spain
facility: Research Site
state: Galicia
city: Madrid
country: Spain
facility: Research Site
city: Bristol
country: United Kingdom
facility: Research Site
city: Sheffield
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Katz DA, Morris JD, Chu MP, David KA, Thieblemont C, Morley NJ, Khan SS, Viardot A, Martin Garcia-Sancho A, Rodriguez-Garcia G, Bastos-Oreiro M, Lee ST, Kormany W, Chen Y, Wong HL, Anderson AA, Katlinskaya Y, Avilion AA, Dai T, Gonzalez-Barca E. Open-label, phase 2 study of blinatumomab after frontline R-chemotherapy in adults with newly diagnosed, high-risk DLBCL. Leuk Lymphoma. 2022 Sep;63(9):2063-2073. doi: 10.1080/10428194.2022.2064981. Epub 2022 May 3.