Ignite Creation Date:
2025-12-24 @ 1:39 PM
Ignite Modification Date:
2025-12-27 @ 10:13 PM
Study NCT ID:
NCT04646395
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-01-30
First Post:
2020-11-17
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Study of Acalabrutinib and Tafasitamab in MZL Patients
Sponsor:
International Extranodal Lymphoma Study Group (IELSG)
Organization:
Study Overview
Official Title:
Phase II Trial of Acalabrutinib in Combination With Tafasitamab in Patients With Previously Treated Marginal Zone Lymphomas (MZL)
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a multicenter open label phase II trial in patients with previously treated Marginal Zone Lymphomas.
The aim of the study is to evaluate the efficacy and the safety of tafasitamab in combination with acalabrutinib.
Twenty-four patients are expected to be enrolled and treated every 28 days with acalabrutinib and tafasitamab for 24 cycles.
The study consists of two parts, which are performed sequentially. The first part is a safety run-in to evaluate the safety data once 6 patients (representing the 25% of the total cohort) have completed the first cycle of treatment. An Independent Data Monitoring Committee (IDMC) will provide an independent assessment of this evaluation.
The second part starts after the outcome of this evaluation and will include the remaining 18 patients. The 6 patients of the safety run-in phase will be considered for the final evaluation of the study.
Between 11 - 13 weeks, patients showing partial or complete response (PR, CR) will continue treatment, while patients showing stable disease (SD) will discontinue it. However, patients in SD who benefit from therapy may continue to be treated, after agreement between the Investigator and the Sponsor.
Patients who complete the 24 cycles of treatment will enter the follow-up phase up to 3 years from patient's last study treatment dose (about 5 years from treatment start).
Patients who discontinue treatment before cycle 24 for any reason will be followed for up to 3 years (every 6 months for the first year and yearly for the second and third year) from the patient's last study treatment dose.
.
The aim of the study is to evaluate the efficacy and the safety of tafasitamab in combination with acalabrutinib.
Twenty-four patients are expected to be enrolled and treated every 28 days with acalabrutinib and tafasitamab for 24 cycles.
The study consists of two parts, which are performed sequentially. The first part is a safety run-in to evaluate the safety data once 6 patients (representing the 25% of the total cohort) have completed the first cycle of treatment. An Independent Data Monitoring Committee (IDMC) will provide an independent assessment of this evaluation.
The second part starts after the outcome of this evaluation and will include the remaining 18 patients. The 6 patients of the safety run-in phase will be considered for the final evaluation of the study.
Between 11 - 13 weeks, patients showing partial or complete response (PR, CR) will continue treatment, while patients showing stable disease (SD) will discontinue it. However, patients in SD who benefit from therapy may continue to be treated, after agreement between the Investigator and the Sponsor.
Patients who complete the 24 cycles of treatment will enter the follow-up phase up to 3 years from patient's last study treatment dose (about 5 years from treatment start).
Patients who discontinue treatment before cycle 24 for any reason will be followed for up to 3 years (every 6 months for the first year and yearly for the second and third year) from the patient's last study treatment dose.
.
Detailed Description:
Marginal zone B cell lymphomas (MZLs) comprise three distinct entities: extranodal MZL (EMZL) of mucosa-associated lymphoid tissue type (MALT) lymphoma, splenic MZL (SMZL) and nodal MZL (NMZL).
Together they represent approximately 5%-15% of all non-Hodgkin lymphomas.
MZL are in general indolent lymphomas with relatively low risk of transformation. The available treatment options can lead to responses but disease recurrence is often observed. For patients with MZL and recurrent disease following initial treatment, currently there is no established standard therapy and new treatment options and treatment combinations are needed.
The proposed trial will evaluate the safety and efficacy of the anti-CD19 monoclonal antibody tafasitamab in combination with the BTK inhibitor acalabrutinib. The B-lymphocyte, lineage specific surface antigen CD19 is broadly and homogeneously expressed in MZLs. This makes CD19 an attractive target for the treatment of MZL patients, in particular those who failed a previous rituximab-containing regimen.
On the other hand, genetic and immunogenetic data point to B-cell receptor signalling as a key oncogenic pathway of MZLs. The activity of single agent ibrutinib in MZLs is an in vivo proof that MZLs are addicted of BTK-driven signalling and that the BCR pathway is a vulnerability of these lymphomas.
The safety profile of the anti CD19 monoclonal antibody tafasitamab and of the BTK inhibitor acalabrutinib indicate the possibility that their combination can be developed without major overlapping side effects.
The proposed trial is a prospective multicenter trial combining tafasitamab and acalabrutinib in patients with MZL (including EMZL, SMZL and NMZL) with disease refractory to or in first or greater relapse after prior systemic therapy.
Together they represent approximately 5%-15% of all non-Hodgkin lymphomas.
MZL are in general indolent lymphomas with relatively low risk of transformation. The available treatment options can lead to responses but disease recurrence is often observed. For patients with MZL and recurrent disease following initial treatment, currently there is no established standard therapy and new treatment options and treatment combinations are needed.
The proposed trial will evaluate the safety and efficacy of the anti-CD19 monoclonal antibody tafasitamab in combination with the BTK inhibitor acalabrutinib. The B-lymphocyte, lineage specific surface antigen CD19 is broadly and homogeneously expressed in MZLs. This makes CD19 an attractive target for the treatment of MZL patients, in particular those who failed a previous rituximab-containing regimen.
On the other hand, genetic and immunogenetic data point to B-cell receptor signalling as a key oncogenic pathway of MZLs. The activity of single agent ibrutinib in MZLs is an in vivo proof that MZLs are addicted of BTK-driven signalling and that the BCR pathway is a vulnerability of these lymphomas.
The safety profile of the anti CD19 monoclonal antibody tafasitamab and of the BTK inhibitor acalabrutinib indicate the possibility that their combination can be developed without major overlapping side effects.
The proposed trial is a prospective multicenter trial combining tafasitamab and acalabrutinib in patients with MZL (including EMZL, SMZL and NMZL) with disease refractory to or in first or greater relapse after prior systemic therapy.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 2019-004396-38 | EUDRACT_NUMBER | None | View |