Ignite Creation Date:
2025-12-24 @ 9:19 PM
Ignite Modification Date:
2026-01-02 @ 9:57 AM
Study NCT ID:
NCT02874404
Status:
COMPLETED
Last Update Posted:
2023-10-05
First Post:
2016-08-17
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
TGR-1202 and Ibrutinib in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Sponsor:
University of Nebraska
Organization:
Study Overview
Official Title:
A Single-Center Phase IIa Study Evaluating the Safety and Tolerability of TGR-1202 and Ibrutinib in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma: A Trial of the Lymphoma Precision Medicine Laboratory
Status:
COMPLETED
Status Verified Date:
2023-09
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 phase IIa trial studies the side effects and how well TGR-1202 and ibrutinib work in treating patients with diffuse large B-cell lymphoma that has returned after a period of improvement or does not respond to treatment. TGR-1202 and ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Detailed Description:
PRIMARY OBJECTIVES:
I. To determine the safety and tolerability of PI3K delta inhibitor TGR-1202 (TGR-1202) and ibrutinib in relapsed and refractory (rel/ref) diffuse large B-cell lymphoma (DLBCL).
SECONDARY OBJECTIVES:
I. To determine the overall response rate (ORR) defined as the sum of complete responses (CR) and partial responses (PR).
II. To determine the event-free survival (EFS), time to response (TTR), and duration of response (DOR) in patients with rel/ref DLBCL.
TERTIARY OBJECTIVES:
I. To evaluate molecular profiling of patient samples (optional lymph node biopsies) obtained at days 0 (pre-treatment; core biopsy), day 8 (fine needle aspiration) and end of treatment (progressive disease or end of study treatment-1 year; core biopsy).
II. To evaluate the baseline characteristics and dynamic shifts in mutational Landscape, transcriptional signatures and intracellular signaling cascades in primary tumor cells.
III. To define the mutational status of 384 genes that mutated in DLBCL, including cluster of differentiation (CD)79B, caspase recruitment domain family member 11 (CARD11), and myeloid differentiation primary response 88 (MYD88).
IV. To evaluate signatures of B-cell receptor signaling and the back-up pathway of oxidative phosphorylation.
V. To measure the basal and induced level of activation of components within parallel signaling pathways downstream of the B-cell receptor.
VI. To monitor changes in T-cell characteristics in response to exposure to TGR-1202 and ibrutinib.
VII. To perform quantitative response evaluation by peripheral blood cell-free deoxyribonucleic acid (DNA) sequencing at enrollment, day 8, 1 month, at every response assessment time point compared to standard radiographic response evaluation by positron emission tomography (PET)/ computed tomography (CT) or CT and end of treatment (progressive disease or end of study treatment-1 year).
VIII. To evaluate the genetic profiling for drug resistance mutations. IX. To evaluate DLBCL subtype analysis by immunohistochemistry compared to Nanostring assessment.
OUTLINE: Patients are assigned to 1 of 3 groups.
GROUP A: Patients receive PI3K delta inhibitor TGR-1202 orally (PO) once daily (QD) on days 1-28 and ibrutinib PO QD on days 9-28 of course 1 and days 1-28 of subsequent courses. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
GROUP B: Patients receive ibrutinib PO QD on days 1-28 and PI3K delta inhibitor TGR-1202 PO QD and days 9-28 of course 1 and days 1-28 of subsequent courses. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
GROUP C: Patients then receive PI3K delta inhibitor TGR-1202 PO QD and ibrutinib PO QD on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days and after 1 year.
I. To determine the safety and tolerability of PI3K delta inhibitor TGR-1202 (TGR-1202) and ibrutinib in relapsed and refractory (rel/ref) diffuse large B-cell lymphoma (DLBCL).
SECONDARY OBJECTIVES:
I. To determine the overall response rate (ORR) defined as the sum of complete responses (CR) and partial responses (PR).
II. To determine the event-free survival (EFS), time to response (TTR), and duration of response (DOR) in patients with rel/ref DLBCL.
TERTIARY OBJECTIVES:
I. To evaluate molecular profiling of patient samples (optional lymph node biopsies) obtained at days 0 (pre-treatment; core biopsy), day 8 (fine needle aspiration) and end of treatment (progressive disease or end of study treatment-1 year; core biopsy).
II. To evaluate the baseline characteristics and dynamic shifts in mutational Landscape, transcriptional signatures and intracellular signaling cascades in primary tumor cells.
III. To define the mutational status of 384 genes that mutated in DLBCL, including cluster of differentiation (CD)79B, caspase recruitment domain family member 11 (CARD11), and myeloid differentiation primary response 88 (MYD88).
IV. To evaluate signatures of B-cell receptor signaling and the back-up pathway of oxidative phosphorylation.
V. To measure the basal and induced level of activation of components within parallel signaling pathways downstream of the B-cell receptor.
VI. To monitor changes in T-cell characteristics in response to exposure to TGR-1202 and ibrutinib.
VII. To perform quantitative response evaluation by peripheral blood cell-free deoxyribonucleic acid (DNA) sequencing at enrollment, day 8, 1 month, at every response assessment time point compared to standard radiographic response evaluation by positron emission tomography (PET)/ computed tomography (CT) or CT and end of treatment (progressive disease or end of study treatment-1 year).
VIII. To evaluate the genetic profiling for drug resistance mutations. IX. To evaluate DLBCL subtype analysis by immunohistochemistry compared to Nanostring assessment.
OUTLINE: Patients are assigned to 1 of 3 groups.
GROUP A: Patients receive PI3K delta inhibitor TGR-1202 orally (PO) once daily (QD) on days 1-28 and ibrutinib PO QD on days 9-28 of course 1 and days 1-28 of subsequent courses. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
GROUP B: Patients receive ibrutinib PO QD on days 1-28 and PI3K delta inhibitor TGR-1202 PO QD and days 9-28 of course 1 and days 1-28 of subsequent courses. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
GROUP C: Patients then receive PI3K delta inhibitor TGR-1202 PO QD and ibrutinib PO QD on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days and after 1 year.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
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 |
|---|---|---|---|---|
| NCI-2016-01082 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| P30CA036727 | NIH | None | https://reporter.nih.gov/quic… | View |