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

This study is currently recruiting participants.
See Contacts and Locations
Verified July 2017 by Matthew Lunning, MD, University of Nebraska Medical Center
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Matthew Lunning, MD, University of Nebraska Medical Center
ClinicalTrials.gov Identifier:
NCT02874404
First received: August 17, 2016
Last updated: July 7, 2017
Last verified: July 2017
  Purpose
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.

Condition Intervention Phase
Recurrent Diffuse Large B-Cell Lymphoma Refractory Diffuse Large B-Cell Lymphoma Drug: Ibrutinib Other: Laboratory Biomarker Analysis Drug: PI3K-delta Inhibitor TGR-1202 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Matthew Lunning, MD, University of Nebraska Medical Center:

Primary Outcome Measures:
  • Incidence of adverse events assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 [ Time Frame: Up to 112 days (course 4) ]

Secondary Outcome Measures:
  • Duration of response [ Time Frame: Time or number of courses between documentation of first response and progression, change of therapy, death, or date of last contact (if still alive without progression), assessed up to 4 years ]
  • Overall response rate defined as the percentage of patients achieving a best response of complete response/complete response, partial response at any disease assessment time point [ Time Frame: Up to 4 years ]
  • Progression-free survival [ Time Frame: Time between study registration and documented progression or death if no progression was observed, assessed up to 4 years ]
  • Time to response [ Time Frame: Time or number of courses between study registration and documentation of first response, assessed up to 4 years ]

Estimated Enrollment: 24
Study Start Date: October 2016
Estimated Study Completion Date: August 30, 2021
Estimated Primary Completion Date: August 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A (PI3K delta inhibitor TGR-1202, ibrutinib)
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
Given PO
Other Names:
  • BTK Inhibitor PCI-32765
  • CRA-032765
  • Imbruvica
  • PCI-32765
Other: Laboratory Biomarker Analysis
Correlative markers
Drug: PI3K-delta Inhibitor TGR-1202
Given PO
Other Names:
  • RP5264
  • TGR-1202
Experimental: Group B (Ibrutinib, PI3K delta inhibitor TGR-1202)
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
Given PO
Other Names:
  • BTK Inhibitor PCI-32765
  • CRA-032765
  • Imbruvica
  • PCI-32765
Other: Laboratory Biomarker Analysis
Correlative markers
Drug: PI3K-delta Inhibitor TGR-1202
Given PO
Other Names:
  • RP5264
  • TGR-1202
Experimental: Group C (PI3K delta inhibitor TGR-1202, ibrutinib)
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
Given PO
Other Names:
  • BTK Inhibitor PCI-32765
  • CRA-032765
  • Imbruvica
  • PCI-32765
Other: Laboratory Biomarker Analysis
Correlative markers
Drug: PI3K-delta Inhibitor TGR-1202
Given PO
Other Names:
  • RP5264
  • TGR-1202

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   19 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
    • Pregnancy testing is not required for post-menopausal or surgically sterilized women
  • Male and female patients of reproductive potential must agree to follow accepted birth control measures throughout the study period and for 30 days after the last dose of either study drug for females and 3 months after the last dose of study drug for males
  • Patient must be able to adhere to the study visit schedule and other protocol requirements
  • Patient must be aware of the neoplastic nature of his/her disease and willingly sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study
  • No serious disease or condition that, in the opinion of the investigator, would compromise the patient's ability to participate in the study

Exclusion Criteria:

  • 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

    • Symptomatic, or history of documented congestive heart failure New York Heart Association (NYHA) functional classification III-IV (NYHA)
    • Corrected QT interval using Fridericia's formula (QTcF) > 470 msec (unless related to pacemaker) on echocardiogram (EKG) within 7 days of initiation of treatment
    • Angina not well-controlled by medication
    • Poorly controlled or clinically significant atherosclerotic vascular disease including cerebrovascular accident (CVA), transient ischemic attack (TIA), angioplasty, cardiac or vascular stenting within 6 months prior to enrollment
  • Prior malignancies within the past 1 year with exception of adequately treated basal cell, squamous cell skin cancer, or thyroid cancer; carcinoma in situ of the cervix or breast; prostate cancer of Gleason grade 6 or less with stable prostate specific antigen (PSA) levels
  • Women who are pregnant or breastfeeding; women who agree to stop breastfeeding would be eligible
  • Known hypersensitivity to either study drug (TGR-1202 or ibrutinib)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02874404

Locations
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198
Contact: Matthew A. Lunning    402-559-5166    mlunning@unmc.edu   
Principal Investigator: Matthew A. Lunning         
Sponsors and Collaborators
Matthew Lunning, MD
National Cancer Institute (NCI)
Investigators
Principal Investigator: Matthew Lunning University of Nebraska
  More Information

Responsible Party: Matthew Lunning, MD, Principal Investigator, University of Nebraska Medical Center
ClinicalTrials.gov Identifier: NCT02874404     History of Changes
Other Study ID Numbers: 345-16
NCI-2016-01082 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
345-16 ( Other Identifier: University of Nebraska Medical Center )
P30CA036727 ( U.S. NIH Grant/Contract )
Study First Received: August 17, 2016
Last Updated: July 7, 2017

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin

ClinicalTrials.gov processed this record on August 16, 2017