Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Follicular

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Follicular Lymphoma

Patients with relapsed or refractory grade 1, 2, or 3A follicular lymphoma will receive TGR-1202.

Treatment will be self-administered on an outpatient basis. Patients will take TGR-1202 800 mg, oral, one tablet daily on a continuous basis. Each cycle lasts 28 days.

TGR-1202

Changchun Deng, MD

The primary objective is to determine the overall response rate (ORR) of TGR-1202 in R/R FL.

Secondary Objectives

* Determine the genetic and other novel biological markers that may be predictive of response or resistance to TGR-1202 in patients with relapsed or refractory FL.
* Describe the Progression Free Survival (PFS), Duration of Response (DoR) after treatment with TGR-1202.
* Describe the number of dose delays and dose reductions and other safety profile.

This is an open label, phase II study of TGR-1202 in patients with relapsed or refractory (R/R) Grade 1, 2, or 3A follicular lymphoma (FL). FL is the most common subtype of indolent lymphoma. The prognosis of FL depends on the histologic grade, stage, treatment and age of the patient. More recently, efforts have been made to find novel regimens for the treatment of relapsed FL that do not contain non-specific cytotoxic agents.

One of the important goals of this phase II study is to discover novel genetic, biochemical, and immunological markers that are associated with the response and safety of TGR-1202 in patients with FL. TGR-1202 blocks PI3K, a signal that is required for cancer to grow.

TGR1202 in Relapsed and Refractory Follicular Lymphoma

Study of the Phosphoinositide-3-Kinase-Delta Inhibitor TGR-1202 in Patients With Relapsed or Refractory Follicular Lymphoma

The sum of patients with partial responses and complete responses.

The length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse.

The time of initial response until documented tumor progression.

The number of instances of patients having a dose of study drug delayed 1 or more days.

The number of instances of patients having to reduce the dosage of study drug based on specified toxicities.

Incidence of Treatment-Emergent Adverse Events \[Safety and Tolerability\] broken down by adverse event and CTCAE v4.0 grade of each event.

TG Therapeutics, Inc.

Columbia University

Patients with relapsed or refractory grade 1, 2, or 3A follicular lymphoma will receive TGR-1202.

TGR-1202: Treatment will be self-administered on an outpatient basis. Patients will take TGR-1202 800 mg, oral, one tablet daily on a continuous basis. Each cycle lasts 28 days.

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Ana Ignat

The data was not collected or analyzed due to the study was terminated prematurely due to slow to accrual and PI left the institution.

Overall Response Rate

Progression Free Survival (PFS) After Treatment With TGR-1202

Duration of Response (DoR) After Treatment With TGR-1202

Number of Dose Delays

Number of Dose Reductions

Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0

Overall Study

All Drugs and Chemicals

Antineoplastic Agents

Antirheumatic Agents

Anti-Inflammatory Agents

Anti-Infective Agents

Antibodies

Antibodies, Monoclonal

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Obinutuzumab

Prednisone

Bendamustine Hydrochloride

Rituximab

Vincristine

Immunomodulating Agents

Lenalidomide

Antibodies, Bispecific

Immunoglobulins

Alkylating Agents

Vinca Alkaloids

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Antineoplastic Agents, Immunological

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Tubulin Modulators

Antimitotic Agents

Angiogenesis Inhibitors

Growth Inhibitors

Epcoritamab (weekly for cycles 1 and 2 and on day 1 of cycles 3-12 for up to 12 cycles) and lenalidomide (daily for days 1-21 of each cycle for up for 12 cycles), cycles will be 28 day cycles.

Choice of therapy to be selected by the Investigator for each patient prior to randomisation. The Investigator will choose between; RCHOP, RCVP, rituximab and bendamustine, rituximab and lenalidomide or bendamustine and obinutuzumab.

Epcoritamab

Bendamustine

The drug used in round 2 is yet to be confirmed, round 2 is estimated to open in Q4 2025 and the record will be updated when the drug has been confirmed

Investigation agent 2

The drug used in round 3 is yet to be confirmed, round 3 is estimated to open in Q3 2027 and the record will be updated when the drug has been confirmed

Investigation agent 3

Trial Coordinator

The aim of the REFRACT clinical trial is to find new therapies with improved outcomes compared to the current standard treatment available, in patients with relapsed or refractory follicular lymphoma. This will be done by comparing patients who have received a new treatment against patients who receive standard treatment based on their response to the treatment received.

In the REFRACT trial patients with relapsed or refractory follicular lymphoma (rrFL) will be randomised (randomly allocated) to receive a new treatment (experimental treatment) or standard treatment which will be chosen by their doctor prior to entering the trial (called investigator choice standard therapy (ICT)). There are 3 treatment rounds which will happen one after another, testing 3 different experimental treatments. The experimental treatment in each round will be compared to ICT. ICT will be a choice of 1 of 5 standard treatment options including RCHOP, RCVP, lenalidomide and rituximab, bendamustine and rituximab or obinutuzumab and bendamustine. Patients in Round 1 (R1) will be randomised using a 1:1 allocation ratio (meaning patients have a 50/50 chance of receiving the experimental treatment). In Round 1 the experimental treatment is epcoritamab combined with lenalidomide. Patients randomised to epcoritamab and lenalidomide will receive up to 12 28-day cycles of therapy; epcoritamab will be delivered as a subcutaneous injection weekly for cycles 1 and 2 and on day 1 of cycles 3-12. Lenalidomide will be taken orally on days 1-21 of each cycle. Patients in Rounds 2 (R2) and 3 (R3) (experimental treatments yet to be determined) will be randomised using a 1:4 allocation ratio in favour of the experimental treatment (meaning patients are more likely to receive the experimental treatment). The study will recruit 284 patients with rrFL over 5 years. The aim is to identify new therapies which have better outcomes compared to ICT based on patients response to treatment (tested by PET scan) after 24 weeks of therapy. Following treatment patients will be followed up yearly until the end of the trial (up to 10 years).

Relapsed Follicular Lymphoma Randomised Trial Against Standard ChemoTherapy

Relapsed Follicular Lymphoma Randomised Trial Against Standard ChemoTherapy (REFRACT): A Randomised Phase II Trial of Investigator Choice Standard Therapy Versus Sequential Novel Therapy Experimental Arms

CMR will be assessed by PET-CT using the Deauville 5-point scale and Lugano 2014 criteria. Patients who die from any cause or relapse/progress prior to this time-point will be considered non-responders. Patients who don't have a PET-CT scan within the protocol defined window or withdraw from the trial prior to this time-point will be considered non outcome evaluable. Patients who undergo stem-cell transplant (SCT) within 24 weeks of randomisation, patients who fail to start treatment and patients whose ineligibility is deemed to impact upon response to treatment will be replaced and hence not included in the analysis of this outcome

Complete metabolic response (CMR) and partial metabolic response (PMR) will be assessed by PET-CT. Patients who die from any cause or relapse/progress prior to this time-point will be considered non-responders. Patients who undergo stem-cell transplant (SCT) within 24 weeks of randomisation, patients who fail to start treatment and patients whose ineligibility is deemed to impact upon response to treatment will be replaced and hence not included in the analysis of this outcome

The time from randomisation to the date of first disease progression or death. Patients who are alive and relapse/progression at the time of analysis will be censored at their date last seen

The time from randomisation to the date of death from any cause. Patients who are alive at the time of analysis will be censored at their date last seen

The time from complete and partial metabolic response by PET-CT to relapse/progression or death from any cause. Patients who are alive and relapse/progression free at the time of analysis will be censored at their date last seen

The time from complete metabolic response by PET-CT to relapse/progression or death from any cause. Patients who are alive and relapse/progression free at the time of analysis will be censored at their date last seen

The time from randomisation to the start date of next treatment for lymphoma. Patients who are responding (CMR or PMR) who receive consolidation radiotherapy will not be considered an event and will be censored at their date last seen if no other treatment for lymphoma is reported. Patients who die without having started next lymphoma treatment will be considered a competing risk at their date of death, and patients who are alive and have not started next lymphoma treatment at the time of analysis will be censored at their date last seen

Collected and reported in accordance with CTCAE version 5 defined as the number of patients who experience one or more grade 3 or 4 adverse events or serious adverse events of any grade

Cancer Research UK

Genmab

University of Birmingham

Symptoms and General Pathology

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, B-Cell, Marginal Zone

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Hematologic Diseases

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

B-cell Lymphoma

Marginal Zone Lymphoma

Diffuse Large B-Cell Lymphoma

Richter Syndrome

Participants with R/R B-cell NHL (including diffuse large B-cell lymphoma \[DLBCL\], follicular lymphoma \[FL\], marginal zone lymphoma \[MZL\], transformed B-cell NHL (B-NHL), and Richter's transformation to DLBCL) will receive BGB-21447 once a day.

Participants with relapsed/refractory (R/R) Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) will receive BGB-21447 once a day.

Participants will receive BGB-21447 with up to two dose levels from Cohort A1 for further evaluation of safety and efficacy.

BGB-21447

BeiGene

This study is testing the safety and tolerability of BGB-21447 monotherapy in participants with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The study aims to determine the maximum tolerated dose (MTD), maximum adminstered dose (MAD), recommended Phase 2 dose (RP2D), and pharmacokinetic profile of the drug. Additionally, preliminary antitumor activity will be characterized. The study is divided into 2 main parts: Part 1 "Monotherapy Dose Finding" and Part 2 "Monotherapy Dose Expansion."

A Study of BGB-21447, a Bcl-2 Inhibitor, in Mature B-Cell Malignancies

A Phase 1/1b Open-Label Dose-Escalation Study of Bcl-2 Inhibitor BGB-21447 in Patients With Mature B-Cell Malignancies

Number of participants with dose limiting toxicities, defined as \[see text in SAP or protocol for specific definition\]

Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) assessed and graded based upon the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0).

TLS will be determined via laboratory values and assessed by the investigator.

In laboratory tumor lysis syndrome, 2 or more metabolic abnormalities must be present during the 24-hour period within 3 days before the start of study drug treatment or up to 7 days afterward. Clinical tumor lysis syndrome requires the presence of laboratory tumor lysis syndrome plus an increased creatinine level, seizures, cardiac dysrhythmia, or death.

defined as the percentage of patients who achieve partial response or better for diffuse large B-cell lymphoma, marginal zone lymphoma, follicular lymphoma, transformed B-NHL, and Richter's transformation to DLBCL as per the Lugano Classification for non-Hodgkin lymphoma

defined as the time from the first response documentation to the date that progression is documented after treatment initiation or death due to any cause, whichever occurs first.

defined as the time from treatment initiation to the first documentation of response.

defined as the time from treatment initiation to the first documented disease progression or death due to any cause, whichever occurs first.

Amino Acids

Venetoclax

Ibrutinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

Ibrutinib (capsule) - 420mg Venetoclax (tablet) - 400mg

Each medication is taken daily. Treatment cycles are 28 days long.

Ibrutinib (capsule) - 560mg Venetoclax (tablet) - 400mg

Each medication is taken daily. Treatment cycles are 28 days long.

Ibrutinib (capsule) - 560mg Venetoclax (tablet) - 600mg

Each medication is taken daily. Treatment cycles are 28 days long.

Ibrutinib (capsule) - 560mg Venetoclax (tablet) - 800mg

Each medication is taken daily. Treatment cycles are 28 days long.

The Phase II dose will be the maximum tolerated dose as determined in the Phase I portion.

Chaitra Ujjani, MD

This is a phase I/II study in which patients will be enrolled in a standard 3+3 design. Once the maximum tolerated dose (MTD) is determined amongst patients with relapsed or refractory grade 1-3a follicular lymphoma, there will be a 17-patient phase II study.

In vitro studies of ibrutinib and venetoclax have noted significant cytotoxicity and synergy in mantle cell lymphoma and chronic lymphocytic leukemia cell lines.Data have demonstrated synergy between the two agents in various other B-cell Non-Hodgkin Lymphoma (NHL) cell lines. The investigators theorize that the combination of ibrutinib and venetoclax will provide dual, yet unique, targeted inhibition for patients with follicular lymphoma, resulting in both significant efficacy and less nonspecific toxicity.

Ibrutinib and Venetoclax in Relapsed and Refractory Follicular Lymphoma

The maximum tolerated dose of Ibrutinib and Venetoclax as determined by number of DLTs observed. • If 0/3 DLT is observed, dose escalation will continue to the next upper dose level. • If ≥ 2/3 DLTs are observed, then the dose finding procedure will be terminated.

• If 1/3 DLT is observed, then 3 additional patients will be enrolled in the same dose level. If no DLT is observed from the additional 3 patients, then dose escalation will continue to the next upper dose level. If any DLT is observed from the 3 additional patients, then the previously lower dose will be chosen as the MTD and the dose finding procedure will be terminated.

Number of participants on the recommended phase II dose level 2, with a partial or complete response, as determined by the revised Lugano Response Criteria for Non-Hodgkin Lymphoma,

Steady-state plasma concentrations of ibrutinib

Steady-state plasma concentrations of venetoclax

Toxicity (attribute and grade) will be summarized for each dose level for all patients who receive at least one dose of study treatment

AbbVie

Pharmacyclics LLC.

Hackensack Meridian Health

Georgetown University

Ibrutinib (capsule) - 420mg Venetoclax (tablet) - 400mg Each medication is taken daily. Treatment cycles are 28 days long. Ibrutinib: Ibrutinib is dispensed as a capsule. Venetoclax: Venetoclax is dispensed as a tablet.

Phase 1- Dose Level 0

Ibrutinib (capsule) - 560mg Venetoclax (tablet) - 400mg Each medication is taken daily. Treatment cycles are 28 days long. Ibrutinib: Ibrutinib is dispensed as a capsule. Venetoclax: Venetoclax is dispensed as a tablet.

Phase 1 - Dose Level 1

Ibrutinib (capsule) - 560mg Venetoclax (tablet) - 600mg Each medication is taken daily. Treatment cycles are 28 days long. Ibrutinib: Ibrutinib is dispensed as a capsule. Venetoclax: Venetoclax is dispensed as a tablet.

Phase 1 - Dose Level 2

Ibrutinib (capsule) - 560mg Venetoclax (tablet) - 800mg Each medication is taken daily. Treatment cycles are 28 days long. Ibrutinib: Ibrutinib is dispensed as a capsule. Venetoclax: Venetoclax is dispensed as a tablet.

Phase 1- Dose Level 3

The Phase II dose will be the maximum tolerated dose as determined in the Phase I portion. Phase II Dose = Dose level 2, Ibrutinib (560mg), Venetoclax (600mg).

Phase II- Dose Level 2

Ibrutinib (capsule) - 420mg Venetoclax (tablet) - 400mg

Each medication is taken daily. Treatment cycles are 28 days long.

Ibrutinib: Ibrutinib is dispensed as a capsule.

Venetoclax: Venetoclax is dispensed as a tablet.

Phase I - Dose Level 0

Ibrutinib (capsule) - 560mg Venetoclax (tablet) - 400mg

Each medication is taken daily. Treatment cycles are 28 days long.

Ibrutinib: Ibrutinib is dispensed as a capsule.

Venetoclax: Venetoclax is dispensed as a tablet.

Phase I - Dose Level 1

Ibrutinib (capsule) - 560mg Venetoclax (tablet) - 600mg

Each medication is taken daily. Treatment cycles are 28 days long.

Ibrutinib: Ibrutinib is dispensed as a capsule.

Venetoclax: Venetoclax is dispensed as a tablet.

Phase I - Dose Level 2

Ibrutinib (capsule) - 560mg Venetoclax (tablet) - 800mg

Each medication is taken daily. Treatment cycles are 28 days long.

Ibrutinib: Ibrutinib is dispensed as a capsule.

Venetoclax: Venetoclax is dispensed as a tablet.

Phase I - Dose Level 3

The Phase II dose will be the maximum tolerated dose as determined in the Phase I portion.

Ibrutinib: Ibrutinib is dispensed as a capsule.

Venetoclax: Venetoclax is dispensed as a tablet.

Phase II Dose

Total

Dose Level 0: Ibrutinib (capsule) - 420mg, Venetoclax (tablet) - 400mg

Each medication is taken daily. Treatment cycles are 28 days long.

Recommended Phase 2 Dose (RP2D)

Recommended Phase II Dose Level = Dose level 2, Ibrutinib (560mg), Venetoclax (600mg).

Dose Level 2

Combined Phase I and Phase II participant on RP2D, Dose Level 2

Dose Level 2 Overall Response Rate

Pharmacokinetics of Ibrutinib

Pharmacokinetics of Venetoclax

Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.03

Idelalisib

Loncastuximab tesirine

Participants will be administered loncastuximab tesirine as an intravenous (IV) infusion on Day 1 of each cycle, where 1 cycle is 3 weeks. Loncastuximab tesirine will be administered at a dose of 150 μg/kg for 2 cycles, then at a dose of 75 μg/kg for subsequent cycles.

Participants will be administered 150 mg idelalisib, orally, twice a day throughout each cycle, where 1 cycle is 4 weeks.

Loncastuximab Tesirine

This study aims to evaluate the efficacy of single agent loncastuximab tesirine compared to idelalisib in participants with relapsed or refractory follicular lymphoma.

Study to Evaluate the Efficacy and Safety of Loncastuximab Tesirine Versus Idelalisib in Participants With Relapsed or Refractory Follicular Lymphoma

A Phase 2 Randomized Study of Loncastuximab Tesirine Versus Idelalisib in Patients With Relapsed or Refractory Follicular Lymphoma (LOTIS-6)

CRR was defined as the percentage of participants who experienced a best overall response (BOR) of complete response (CR) assessed prior to any subsequent anticancer treatment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
TGR1202 in Relapsed and Refractory Follicular Lymphoma	NCT03178201	Follicular Lymp...	TGR-1202	18 Years -	Columbia University
TGR1202 in Relapsed and Refractory Follicular Lymphoma	NCT03178201	Follicular Lymp...	TGR-1202	18 Years -	Columbia University
Relapsed Follicular Lymphoma Randomised Trial Against Standard ChemoTherapy	NCT05848765	Relapsed Follic... Refractory Foll...	Epcoritamab Lenalidomide Rituximab Obinutuzumab Bendamustine Vincristine Doxorubicin Cyclophosphamid... Prednisone Investigation a... Investigation a...	18 Years -	University of Birmingham
A Study of BGB-21447, a Bcl-2 Inhibitor, in Mature B-Cell Malignancies	NCT05828589	Relapsed Non-Ho... Refractory Non-... Relapsed Chroni... Refractory Chro... Relapsed Follic... Relapsed Margin... Relapse Diffuse... Relapsed Small ... Refractory Foll... Refractory Marg... Refractory Smal... Richter Transfo... Refractory Diff... Transformed Non...	BGB-21447	18 Years -	BeiGene
A Study of BGB-21447, a Bcl-2 Inhibitor, in Mature B-Cell Malignancies	NCT05828589	Relapsed Non-Ho... Refractory Non-... Relapsed Chroni... Refractory Chro... Relapsed Follic... Relapsed Margin... Relapse Diffuse... Relapsed Small ... Refractory Foll... Refractory Marg... Refractory Smal... Richter Transfo... Refractory Diff... Transformed Non...	BGB-21447	18 Years -	BeiGene
Ibrutinib and Venetoclax in Relapsed and Refractory Follicular Lymphoma	NCT02956382	Refractory Foll... Relapsed Follic...	Ibrutinib Venetoclax	18 Years -	Georgetown University
Study to Evaluate the Efficacy and Safety of Loncastuximab Tesirine Versus Idelalisib in Participants With Relapsed or Refractory Follicular Lymphoma	NCT04699461	Relapsed Follic... Refractory Foll...	Loncastuximab T... Idelalisib	18 Years -	ADC Therapeutics S.A.
A Phase III Multicenter, Randomized Study Comparing RIT Vs ASCT in Patients With Relapsed/Refractory (FL)	NCT01827605	Relapsed Follic...	ZEVALIN BEAM	18 Years - 65 Years	Fondazione Italiana Linfomi - ETS
Phase 2 Study of VELCADE (Bortezomib) in Patients With Relapsed Follicular Lymphoma	NCT00715208	Relapsed Follic...	rituximab cyclophosphamid... doxorubicin VELCADE prednisone	18 Years -	Millennium Pharmaceuticals, Inc.
Study to Evaluate the Efficacy and Safety of Loncastuximab Tesirine Versus Idelalisib in Participants With Relapsed or Refractory Follicular Lymphoma	NCT04699461	Relapsed Follic... Refractory Foll...	Loncastuximab T... Idelalisib	18 Years -	ADC Therapeutics S.A.

Spots Global Cancer Trial Database for relapsed follicular lymphoma