DLBCL, NHL, Non-hodgkin's Lymphoma, Diffuse Large B Cell Lymphoma
Conditions
Keywords
Acalabrutinib, CALQUENCE®, ACP-196, Platform study, Master protocol, PRISM, Hu-5F9, Rituximab, ATR, STAT3, Anti-CD47, BRD4
Brief summary
This is a Phase 1 platform protocol designed to evaluate various targeted agents for the treatment of relapsed/refractory aggressive Non-Hodgkin's Lymphoma (NHL).
Detailed description
This is a Phase 1 platform protocol designed to evaluate various targeted agents for the treatment of relapsed/refractory aggressive Non-Hodgkin's lymphoma (NHL). Each study arm will be conducted in a predefined disease subset. All study arms are open label and allocation to each study arm will not be randomized. As this master platform protocol has multiple study arms, subjects can be screened for several study arms at once. Likewise, a subject who ends participation in one study arm may be rescreened for participation in another (separate) study arm. The primary objective of the study is to evaluate the safety of targeted agents for the treatment of relapsed/refractory aggressive Non-Hodgkin's Lymphoma (NHL). This protocol has a modular design, with the potential for future treatment arms to be added via protocol amendment.
Interventions
DRUGAZD9150
AZD9150 will be administered as a 1-hour intravenous (IV) infusion on Days 1, 3, 5 of Cycle 1, followed by weekly infusions (starting Day 8 of Cycle 1 and beyond).
DRUGAcalabrutinib
Acalabrutinib will be administered orally twice daily (bid).
DRUGAZD6738
AZD6738 will be administered orally twice daily (bid).
DRUGHu5F9-G4
HU5F9-G4 infusions will be given on Weekly (Day 1, 8, 15, and 22) during the first two 28-day cycles, then will be given every two weeks (Day 1 and Day 15) in Cycle 3 and beyond.
DRUGRituximab
Rituximab infusions will be given Weekly starting on Day 8 (Day 8, 15, and 22) during the first 28-day cycle (4 weeks), then Day 1 of each 4 week cycle for Cycles 2-6. Starting with Cycle 8, Rituximab will be infused on Day 1 of every other cycle (every 8 weeks).
DRUGAZD5153
AZD5153 will be administered orally once per day (qd).
Sponsors
AstraZeneca
Acerta Pharma BV
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
Inclusion Criteria For All Arms: 1. Diagnosis of relapsed/refractory aggressive Non Hodgkin's Lymphoma (NHL) with histology based on established World Health Organization (WHO) criteria. 2. Must have received ≥1 prior line of therapy for the treatment of current histology, there are no known curative treatment options available, or subject ineligible for potential curative options. 3. Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy. Not applicable for cutaneous lesions. 4. ECOG performance status of ≤2. Inclusion Criteria for Arm 1: 1\. Must have previously received rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate, and prednisone or equivalent regimen with stem-cell rescue. Or who are ineligible for highdose chemotherapy with stem-cell rescue and/or chimeric antigen receptor (CAR) T cell therapy. Ineligibility for high-dose therapy with stem cell rescue and/or CAR T-cell therapy will be determined by the investigator. Inclusion Criteria for Arm 2: 1\. Must have previously received rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate, and prednisone or equivalent regimen with stem-cell rescue. Or who are ineligible for highdose chemotherapy with stem-cell rescue and/or chimeric antigen receptor (CAR) T-cell therapy. Ineligibility for high-dose therapy with stem cell rescue and/or CAR T-cell therapy will be determined by the investigator. Inclusion Criteria for Arm 3: 1\. Must have previously received rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate, and prednisone or equivalent regimen with stem-cell rescue. Or who are ineligible for highdose chemotherapy with stem-cell rescue and/or chimeric antigen receptor (CAR) T cell therapy. Ineligibility for high-dose therapy with stem cell rescue and/or CAR T-cell therapy will be determined by the investigator. Inclusion Criteria for Arm 4: 1\. Must have previously received rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate, and prednisone or equivalent regimen with stem-cell rescue. Or who are ineligible for highdose chemotherapy with stem-cell rescue and/or chimeric antigen receptor (CAR) T cell therapy. Ineligibility for high-dose therapy with stem cell rescue and/or CAR T-cell therapy will be determined by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of the study treatments when given in combination [Incidence of adverse events] | Through to study completion, an average of 1 year | Incidence of adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of response (DOR) using RECIL 2017 response criteria for the anti-tumour activity of each therapy. | Through to study completion, an average of 1 year | Duration of Response (DOR) is defined as the time from the first objective response of CR or PR to the time of documented disease progression or death due to any cause, whichever occurs first. |
| Progression free survival (PFS) using RECIL 2017 response criteria for the anti-tumour activity of each therapy. | Through to study completion, an average of 1 year | Progression free survival (PFS) is defined as the time from first dose date to documented objective disease progression, or death from any cause, whichever occurs first. Disease progression will be determined by the investigators per standard response criteria as outlined in each respective study arm. |
| Overall Survival (OS) | From the beginning of treatment until the date of death from any cause, assessed up to 12 months | Overall Survival (OS) is defined as the time from first dose until the date of death from any cause. |
| Peak plasma concentration (Cmax) of Study Drug A (Arm 1) | Samples will be collected predose and 1, 4, 6 hours postdose on Cycle 1 Day 8 only; then predose and approximately 1 hr (end of infusion of Study Drug A) on Day 1 of every odd cycle starting with Cycle 3 through study completion, an average of 1 year | — |
| Peak plasma concentration (Cmax) of Study Drug B (Arm 2) | Samples will be collected predose and 1, 4, 8 hours postdose on Cycle 1 Day 8 only; then predose on Cycle 2 Day 1 and Cycle 3 Day 1 | — |
| Area under the plasma concentration versus time curve (AUC) of Study Drug A (Arm 1) | Samples will be collected predose and 1, 4, 6 hours postdose on Cycle 1 Day 8 only; then predose and approximately 1 hr (end of infusion of Study Drug A) on Day 1 of every odd cycle starting with Cycle 3 through study completion, an average of 1 year | — |
| Assessment of the efficacy of each treatment by evaluation of overall response rate using RECIL 2017 response criteria | Through to study completion, an average of 1 year | The overall response rate (ORR) is defined as the rate of subjects who achieve either a partial response (PR) or complete response (CR) as assessed by investigators before receiving any other anticancer therapy. |
| Presence of Anti-Drug Antibody (ADA) titres in subjects treated with Study Drug A | Samples will be collected predose on Days 1 and 8 of Cycle 1 and predose on Day 1 of every odd cycle starting with Cycle 3 | — |
| Peak plasma concentration (Cmax) of acalabrutinib (Arm 1) | Samples will be collected predose and 1, 4, 6 hours postdose on Cycle 1 Day 8 only | — |
| Area under the plasma concentration versus time curve (AUC) for acalabrutinib (Arm 1) | Samples will be collected predose and 1, 4, 6 hours postdose on Cycle 1 Day 8 only | — |
| Peak plasma concentration (Cmax) of acalabrutinib (Arm 2) | Samples will be collected predose and 1, 4, 8 hours postdose on Cycle 1 Day 8 only; then predose on Cycle 2 Day 1 and Cycle 3 Day 1 | — |
| Area under the plasma concentration versus time curve (AUC) for acalabrutinib (Arm 2) | Samples will be collected predose and 1, 4, 8 hours postdose on Cycle 1 Day 8 only; then predose on Cycle 2 Day 1 and Cycle 3 Day 1 | — |
| Area under the plasma concentration versus time curve (AUC) of Study Drug B (Arm 2) | Samples will be collected predose and 1, 4, 8 hours postdose on Cycle 1 Day 8 only; then predose on Cycle 2 Day 1 and Cycle 3 Day 1 | — |
Countries
United Kingdom, United States
Outcome results
None listed