Chronic Lymphocytic Leukaemia or Small Lymphocytic Lymphoma With Unmutated IGHV
Conditions
Keywords
Leukaemia, Lymphoma, Monoclonal IgG4 antibody, Consolidation therapy, Therapeutic benefit, Induction therapy, B-cell malignancy
Brief summary
The purpose of this study is to evaluate the therapeutic benefit and safety of subcutaneous (SC) Surovatamig monotherapy as consolidation therapy in patients with Chronic Lymphocytic Leukaemia (CLL)/ Small Lymphocytic Lymphoma (SLL) with unmutated IGHV (uIGHV).
Detailed description
This is a Phase III global, randomised, open-label, multicentre study. The study will consist of 2 sequential parts- the Dose Optimisation and Safety Run-in part and the Phase-III part. During the dose optimisation and safety run-in part, Surovatamig will be initiated in 2 dose levels. This part will help to determine the recommended phase III dose (RP3D) of Surovatamig to be used in Phase III part. Phase III would comprise of 2 arms, Arm A where the Surovatamig dose (RP3D) will be administered as a consolidation therapy (post standard of care \[SOC\] induction therapy) and Arm B where participants will be observed. In Phase 3 participants will be randomized in a 1:1 ratio to Arm A or Arm B.
Interventions
DRUGSurovatamig
Surovatamig will be administered as a subcutaneous injection.
Sponsors
AstraZeneca
Parexel
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Documented diagnosis of CLL/SLL with genomic features defined by unmutated IGHV. * Treatment received and response at the end of 1L (first-line) finite therapy. * Participants with SLL (except those in CR in Phase III part) must have measurable disease (nodal or extranodal) with at least one measurable target lesion. * ECOG performance status of 0 to 2. * Adequate haematologic, liver, renal and cardiac function. * Female participants: must be either women not of childbearing potential or must use a highly effective form of contraception. * Male participants who intend to be sexually active with females of childbearing potential must agree to use barrier contraception (eg, condoms).
Exclusion criteria
* Suspected or confirmed transformation of CLL/SLL to a more aggressive form of lymphoma (ie, Richter's transformation, prolymphocytic leukaemia, or DLBCL). * Evidence of active or history of Central Nervous System (CNS) involvement by CLL/SLL. * History of or ongoing confirmed progressive multifocal leukoencephalopathy. * Participants who have any concurrent or history of malignancy. * Participants with: * Active or uncontrolled infection (including Epstein-Barr virus-EBV) requiring systemic therapy. * Participants with known history of Heamophagocytic lymphohistiocytosis (HLH). * Human Immunodeficiency Virus (HIV) infection, or participants with chronic or active infection with Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV). * Major cardiac abnormalities. * Prior CLL/SLL-specific therapies. * Requires chronic immunosuppressive therapy for active autoimmune/inflammatory condition or prior allogeneic stem cell or solid organ transplant. * Major surgical procedure. * Known hypersensitivity to surovatamig or any of the excipients of the product.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DOSRI- Number of participants with adverse events (AEs) and Serious Adverse Events (SAEs) | Up to 5 years | To assess the safety and tolerability of SC surovatamig as consolidation therapy using dose optimisation in CLL/SLL participants with uIGHV. Also, to determine the RP3D of SC surovatamig monotherapy as consolidation therapy in CLL/SLL participants with uIGHV. |
| Phase III- Progression Free Survival (PFS) | Until disease progression or death (up to 5 years) | PFS is defined as the time from date of randomisation until disease progression or death due to any cause, whichever occur first based on International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria, as assessed by independent review committee (IRC). |
| DOSRI- Number of participants with study intervention discontinuations, dose reductions and dose delays due to AEs | Up to 5 years | To assess the safety and tolerability of SC surovatamig as consolidation therapy using dose optimisation in CLL/SLL participants with uIGHV. Also, to determine the RP3D of SC surovatamig monotherapy as consolidation therapy in CLL/SLL participants with uIGHV. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to 5 years | ORR is defined as the proportion of participants achieving either a partial response (PR) or complete response (CR)/complete response with incomplete haematological recovery (CRi) based on response criteria iwCLL 2018, as assessed by IRC or investigator at any point during therapy/observation. |
| Complete Response rate (CR rate) | Up to 5 years | CR rate is defined as the proportion of participants achieving a CR or CRi as best response based on response criteria for iwCLL 2018. |
| Duration of response (DoR) | Up to 5 years | The DoR is defined as the time from the date of first documented response until date of documented progression based on response criteria for iwCLL 2018. |
| DOSRI- PFS | Until disease progression or death (up to 5 years) | PFS for Safety Run-in phase is defined as the time from first dose until the date of documented progression or death due to any cause whichever comes first, based on iwCLL 2018 criteria. |
| Overall Survival (OS) | Up to 5 years | OS is defined as the time from first dose until death due to any cause. |
| Serum concentrations of Surovatamig | At pre-defined intervals from date offirst dose (C1D1) up to 30 days from last dose (approximately 5 years) | To characterise the serum concentration of SC surovatamig as consolidation therapy in CLL/SLL participants with uIGHV. |
| Maximum concentration observed (Cmax) | At pre-defined intervals from date of first dose up to 30 days from last dose (approximately 5 years) | To characterise the pharmacokinetics (PK) of SC surovatamig as consolidation therapy in CLL/SLL participants with uIGHV. |
| Time to Maximum Concentration (tmax) | At pre-defined intervals from date of first dose up to 30 days from last dose (approximately 5 years) | To characterise the PK of SC surovatamig as consolidation therapy in CLL/SLL participants with uIGHV. |
| Trough concentration (Ctrough) | At pre-defined intervals from date of first dose up to 30 days from last dose (approximately 5 years) | To characterise the PK of SC surovatamig as consolidation therapy in CLL/SLL participants with uIGHV. |
| Number of participants with Anti-drug antibodies (ADA) | At predefined intervals from the date of first dose to approximately 5 years | DOSRI- To evaluate the immunogenicity of SC surovatamig as consolidation therapy in CLL/SLL participants with uIGHV. Phase III- To determine the immunogenicity of SC surovatamig in CLL/SLL participants with uIGHV. |
| Phase III- PFS | Until disease progression or death (up to 5 years) | PFS is defined as the time from date of randomisation until disease progression or death due to any cause , whichever comes first based on iwCLL 2018 criteria, as assessed by investigator. |
| Phase III- Number of participants with AEs and SAEs | Up to 5 years | To assess safety and tolerability of SC surovatamig compared to observation in CLL/SLL participants with uIGHV. |
Countries
Australia, Canada, Turkey (Türkiye), United Kingdom
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed