TGR-1202 and Ibrutinib in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

NCT02874404 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: 0345-16-FBNCI-2016-01082P30CA036727
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Recurrent Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Participants With Adverse Events

  Notable serious or recurrent adverse events (SAEs or AEs) of interest occurring across all cycles regardless of attribution assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

  Up to 112 days (course 4)

Secondary Outcomes (2)

• Overall Response Rate (ORR)

  Up to 4 years

• Estimated Progression-free Survival (PFS) at 6 Months

  Time between study registration and documented progression or death if no progression was observed, assessed up to 4 years (6 Month estimate shown)

Study Arms (3)

Group A (PI3K delta inhibitor TGR-1202, ibrutinib)

EXPERIMENTAL

Patients receive PI3K delta inhibitor TGR-1202 PO 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.

Drug: Ibrutinib; Other: Laboratory Biomarker Analysis; Drug: PI3K-delta Inhibitor TGR-1202

Group B (Ibrutinib, PI3K delta inhibitor TGR-1202)

EXPERIMENTAL

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.

Drug: Ibrutinib; Other: Laboratory Biomarker Analysis; Drug: PI3K-delta Inhibitor TGR-1202

Group C (PI3K delta inhibitor TGR-1202, ibrutinib)

EXPERIMENTAL

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.

Drug: Ibrutinib; Other: Laboratory Biomarker Analysis; Drug: PI3K-delta Inhibitor TGR-1202

Interventions

Ibrutinib DRUG

Given PO

Also known as: BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

Group A (PI3K delta inhibitor TGR-1202, ibrutinib); Group B (Ibrutinib, PI3K delta inhibitor TGR-1202); Group C (PI3K delta inhibitor TGR-1202, ibrutinib)

Laboratory Biomarker Analysis OTHER

Correlative markers

Group A (PI3K delta inhibitor TGR-1202, ibrutinib); Group B (Ibrutinib, PI3K delta inhibitor TGR-1202); Group C (PI3K delta inhibitor TGR-1202, ibrutinib)

PI3K-delta Inhibitor TGR-1202 DRUG

Given PO

Also known as: RP5264, TGR-1202

Group A (PI3K delta inhibitor TGR-1202, ibrutinib); Group B (Ibrutinib, PI3K delta inhibitor TGR-1202); Group C (PI3K delta inhibitor TGR-1202, ibrutinib)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diffuse large B-cell lymphoma (DLBCL) or transformed DLBCL
• Hematoxylin and eosin (H\&E) stain and immunohistochemistry (IHC) slides or a representative formalin-fixed, paraffin-embedded (FFPE) tissue block along with the pathology report from initial diagnosis, (as well as, an optional 8 unstained slides of 4 micron thickness to store for future IHC and DNA specified research use), should be sent to be reviewed, and the diagnosis confirmed by University of Nebraska Medical Center (UNMC) (retrospective diagnostic review: treatment may commence prior to the UNMC review); please NOTE: the diagnostic H\&E slide and IHC slides will be returned after review; only the optional 8 unstained slides will be retained and stored for future unspecified research use
• Patients with relapsed or refractory DLBCL that has relapsed post-transplant or that has been determined to be ineligible or unsuitable for transplant; patients must have to have received at least one prior systemic therapy
• Patients must have measurable (\>= 1.5 cm) or evaluable disease; baseline measurements and evaluations must be obtained within 6 weeks of registration to the study; abnormal PET scans will not constitute evaluable disease, unless verified by CT scan or other appropriate imaging; measurable disease must have at least one objective measurable disease parameter; a clearly defined, bi-dimensionally measurable defect or mass measuring at least 1.5 cm in diameter on a CT scan will constitute measurable disease; proof of lymphoma in the liver is required by a confirmation biopsy; skin lesions can be used as measurable disease provided bi-dimensional measurements are possible
• Absolute neutrophil count (ANC) \>= 1.0 x 10\^9/L
• By automated or manual review, whichever is greatest
• Platelets \>= 100 x 10\^9/L:
• Unless due to bone marrow infiltration then eligible if platelets \> 50 x 10\^9/L)
• Total bilirubin =\< 1.5 x upper normal limit if documented hepatic involvement with lymphoma, or =\< 5 x upper normal limit if history of Gilbert's disease
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x upper limit of normal (ULN) if no liver involvement or =\< 5 x the ULN if documented liver involvement
• Creatinine =\< 2.0 mg/dL OR calculated creatinine clearance \>= 50 mL/min (as calculated by the Cockcroft-Gault method)
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 or expected survival duration of \> 2 months
• Ability to swallow and retain oral medication
• Women must not be pregnant or breast-feeding
• All female patients of child-bearing potential must have a negative serum pregnancy test within 2 weeks prior to treatment to rule out pregnancy

You may not qualify if:

• Currently receiving cancer therapy (i.e., chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy, and surgery and/or tumor embolization) or any investigational drug within 7 days of cycle 1/day 1, 14 days of cycle 1/day 1 for limited palliative radiation, and/or five half-live of an oral therapy
• Corticosteroid therapy started at least 7 days prior to initiation of treatment (prednisone =\< 10 mg daily or equivalent) is allowed as clinically warranted); topical or inhaled corticosteroids are permitted
• Major surgery or a wound that has not fully healed within 4 weeks of enrollment
• History of stroke or intracranial hemorrhage within 6 months prior to enrollment
• Requires anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon)
• Vaccinated with live, attenuated vaccines within 4 weeks of enrollment
• Autologous hematologic stem cell transplant within 3 months of study entry
• Allogeneic hematologic stem cell transplant within 12 months of study entry
• Active graft versus-host disease and must not be on immunosuppression
• Wide field radiotherapy within 28 days of cycle 1/day 1 or active side effects of such therapy
• Active hepatitis B (hepatitis B virus \[HBV\]) or C (hepatitis C virus \[HCV\]) infection (negative serology required excluding those with are seropositive due to prior vaccination) and/or known history of human immunodeficiency virus (HIV)
• Primary central nervous system involvement only
• Require treatment with strong cytochrome P450 family 3 subfamily A (CYP3A) inhibitors
• Known history of drug-induced liver injury, alcoholic liver disease, primary biliary cirrhosis, ongoing extra-hepatic obstruction caused by stones, cirrhosis of the liver or portal hypertension
• Any life-threatening illness, severe and/or uncontrolled medical condition, or organ system dysfunction, laboratory abnormality, psychiatric illness or other condition which, in the Investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, put the study outcomes at undue risk or affect their participation in the study such as

Sponsors & Collaborators

• University of Nebraska: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

ibrutinib; umbralisib

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Dr. Matthew Lunning, DO, Associate Professor
• Organization: University of Nebraska Medical Center

mlunning@unmc.edu

402-559-7164

Study Officials

• Matthew A Lunning, DO

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2016
• First Posted: August 22, 2016
• Study Start: October 7, 2016
• Primary Completion: July 1, 2019
• Study Completion: July 1, 2019
• Last Updated: October 5, 2023
• Results First Posted: February 26, 2020

Record last verified: 2023-09

Locations

US (1)