High-risk Diffuse Large B-cell Lymphoma Clinical Trial
Official title:
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.
| Verified date | September 2020 |
| Source | Amgen |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Terminated |
| Enrollment | 10 |
| Est. completion date | September 30, 2019 |
| Est. primary completion date | September 30, 2019 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 100 Years |
| Eligibility |
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. |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Research Site | Clayton | Victoria |
| Australia | Research Site | Geelong | Victoria |
| Australia | Research Site | St Leonards | New South Wales |
| Australia | Research Site | Westmead | New South Wales |
| Belgium | Research Site | Charleroi | |
| Belgium | Research Site | Leuven | |
| Belgium | Research Site | Liege | |
| France | Research Site | Créteil Cedex | |
| France | Research Site | Lille | |
| France | Research Site | Marseille | |
| France | Research Site | Montpellier cedex 5 | |
| France | Research Site | Paris Cedex 10 | |
| France | Research Site | Pessac Cedex | |
| France | Research Site | Pierre Benite Cedex | |
| France | Research Site | Rouen | |
| Greece | Research Site | Athens | |
| Greece | Research Site | Athens | |
| Greece | Research Site | Thessaloniki | |
| Italy | Research Site | Bergamo | |
| Italy | Research Site | Brescia | |
| Italy | Research Site | Firenze | |
| Italy | Research Site | Milano | |
| Italy | Research Site | Palermo | |
| Italy | Research Site | Torino | |
| Switzerland | Research Site | Bellinzona | |
| Switzerland | Research Site | Bern | |
| Switzerland | Research Site | Lausanne | |
| Switzerland | Research Site | Zurich | |
| United States | Research Site | Atlanta | Georgia |
| United States | Research Site | Cleveland | Ohio |
| United States | Research Site | Dallas | Texas |
| United States | Research Site | Maywood | Illinois |
| Lead Sponsor | Collaborator |
|---|---|
| Amgen |
United States, Australia, Belgium, France, Greece, Italy, Switzerland,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | MRD-Negative Rate at the End of Cycle 1 | 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). | 12 weeks (84 days) | |
| Secondary | Kaplan-Meier Estimate: Progression-Free Survival (PFS) | 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. | up to 1 year from first dose of blinatumomab | |
| Secondary | Kaplan-Meier Estimate: Duration of MRD-Negative Status | 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. | up to 1 year from first dose of blinatumomab | |
| Secondary | Kaplan-Meier Estimate: Overall Survival (OS) | 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. | up to 1 year from first dose of blinatumomab | |
| Secondary | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 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). | 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. |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT03023878 -
Safety and Efficacy of Blinatumomab in Adults With Newly Diagnosed High-risk Diffuse Large B-Cell Lymphoma
|
Phase 2 |