Secondary Immune Deficiency
Conditions
Keywords
Hematologic Malignancies, B-cell acute lymphoblastic leukemia (B-ALL), Multiple myeloma (MM), Chronic lymphocytic leukemia (CLL), Small lymphocytic lymphoma (SLL), Non-Hodgkin lymphomas (NHL), T-cell engager bispecific antibody (TCE BsAb) therapy, Hypogammaglobulinemia, Lowered serum immunoglobulin levels
Brief summary
This is a prospective, multicenter, open-label, single-arm study to assess the efficacy, safety, and pharmacokinetics (PK) of IgPro20 in adults with hematologic malignancies treated with B-cell targeting Chimeric antigen receptor T-cell (CAR T-cell) and T-cell redirecting therapies (such as T-cell engager bispecific antibody \[TCE BsAb\] therapy). The primary objective is to demonstrate that true annualized rate of serious bacterial infection (SBIs) is less than (\<) 1.0. This study includes two cohorts: 1. Loading Cohort: Participants with serum immunoglobulin G (IgG) \< 500 milligrams per deciliter (mg/dL) at Screening, with or without ongoing immunoglobulin replacement therapy (IgRT) during Screening, who must have received five doses of IgPro20 during the Initial Treatment Period. 2. Maintenance-only Cohort: Participants with serum IgG greater than or equal to (≥) 500 mg/dL and ongoing IgRT at Screening, who must have received one dose of IgPro20 during the Initial Treatment Period.
Interventions
BIOLOGICALIgPro20
IgPro20 infusion administered SC.
Sponsors
CSL Behring
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is open-label study.
Intervention model description
This is single group open-label study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants greater than or equal to (≥) 18 years of age at the time of providing written informed consent. * Confirmed diagnosis of B-cell hematologic malignancy (ie, Multiple myeloma \[MM\], Chronic lymphocytic leukemia \[CLL\], Non-Hodgkin lymphoma \[NHL\], or BALL) according to applicable diagnostic criteria. * Participants treated with Chimeric antigen receptor T-cell (CAR T-cell) therapy or TCE BsAb and are: 1. At least 2 months after receipt of an approved CAR T-cell therapy for the B-cell hematologic malignancy at the time of Screening, or 2. At least 1 month after initiation of an approved TCE BsAb therapy for the B-cell hematologic malignancy at the time of Screening and expected to continue with the therapy. * Documented partial or complete response to CAR T-cell or TCE BsAb therapy based on applicable response criteria at the time of Screening: 1. CLL based on International Workshop on Chronic Lymphocytic Leukemia response criteria 2. MM based on International Myeloma Working Group response criteria 3. NHL based on Lugano Classification criteria 4. B-ALL based on National Comprehensive Cancer Network guidelines * IgG level (excluding paraprotein, if relevant) at Screening: If participant has ongoing IgRT (intravenous immunoglobulin \[IVIG\] or subcutaneous immunoglobulin \[SCIG\]) for SID during Screening, then any IgG level at Screening is acceptable for enrollment. Participants with IgG less than (\<) 500 milligrams per deciliter (mg/dL) are assigned to the Loading Cohort, participants with IgG ≥ 500 mg/dL are assigned to the Maintenance-only Cohort. * IgG level (excluding paraprotein, if relevant) at Screening: If participant does not have ongoing IgRT (IVIG for \> 8 weeks or SCIG for \> 2 weeks) for SID during Screening and are not expected to receive IgRT during Screening, then IgG \< 500 mg/dL is required for enrollment (participant is assigned to the Loading Cohort)
Exclusion criteria
* Documented history of diseases for which IgRT may be indicated: primary immune deficiency, chronic inflammatory demyelinating polyneuropathy, Guillain-Barré syndrome, immune thrombocytopenia, Kawasaki disease, Lambert-Eaton myasthenic syndrome, multifocal motor neuropathy, myasthenia gravis, stiff person syndrome, solid organ transplant, and rejection prior to Screening. * History of thromboembolic event (TEE) within 6 months before Screening. * Eastern Cooperative Oncology Group performance status \> 1. * Presence of any systemic active infection at Screening. * Participants on any prohibited therapies, including anti-infective treatments. * Absolute neutrophil count \< 1 × 10\*9/L (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade 3 or worse), unless proven to be due to the underlying disease and raised above the limit by granulocyte colony-stimulating factor. * Concurrent participation in other interventional clinical studies. Note: a participant may be enrolled if their participation in the other study will not jeopardize their safety and / or the scientific validity of this study (eg, an observational study, a long-term safety follow-up of an interventional study, diagnostic device studies, phase 4 studies with medicines used within their approved indication); the investigator may consult with the medical monitor.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Serious Bacterial Infections (SBIs) per Participant | Up to Month 12 | The SBIs includes: bacteremia / sepsis, bacterial meningitis, osteomyelitis / septic arthritis, bacterial pneumonia, and visceral abscess. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Infections per Participant | Up to Month 12 | — |
| Number of Common Terminology Criteria for Adverse Events (CTCAE) >= Grade 3 Infections per Participant | Up to Month 12 | As per CTCAE, Grade 3 is defined as Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living (self-care activities of daily living refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden). Grade 4: Life-threatening consequences; urgent intervention indicated and Grade 5: Death related to adverse event. Infections of CTCAE Grade 3 or worse will be reported. |
| Number of Days Hospitalized due to Infections | Up to Month 12 | — |
| Number of Days With Anti-infectives Use | Up to Month 12 | — |
| Number of Infection-related Deaths and Complications | Up to Month 12 | — |
| Number of Infection-related Requirement for Intravenous (IV) Therapy | Up to Month 12 | — |
| Number of Infection-related Requirement for Hospitalization per Participant | Up to Month 12 | — |
| Number of Participants with Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs), Infusion Site Reaction and Other Local Reactions | Up to Month 12 | In this study, thromboembolic events are treated as AESIs. The following 3 narrow standardized Medical Dictionary for Regulatory Activities (MedDRA) queries are used for TEE evaluation: * Embolic and thrombotic events, arterial * Embolic and thrombotic events, venous * Embolic and thrombotic events, vessel type unspecified, and mixed arterial and venous. |
| Trough Concentrations of Serum IgG | Up to Week 56 | — |
| Area Under the Serum Concentration Time Curve (AUC) for IgG From Timepoint Zero to tau (AUC[0-t]) | Before IgPro20 dosing at Week 52 and up to Week 54 (after the last dose of IgPro20) | — |
| Maximal Serum Concentration (Cmax) of IgG | Before IgPro20 dosing at Week 52 and up to Week 54 (after the last dose of IgPro20) | — |
| Time to Maximal Serum Concentration (Tmax) of IgG | Before IgPro20 dosing at Week 52 and up to Week 54 (after the last dose of IgPro20) | — |
Countries
Belgium, Canada, Czechia, Denmark, France, Germany, Italy, Poland, Spain, United Kingdom, United States
Contacts
CONTACTTrial Registration Coordinator
Outcome results
None listed