Combination of Pembrolizumab With TGR-1202 in Patients With Relapsed/Refractory CLL and B-cell NHL

NCT03283137 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: IRB17-0901
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

Brief Summary

This study will be a standard 3+3 design with a lead in of TGR-1202 at dose of 600mg (dose level 1) or 800mg daily (dose level 2) for 6 weeks, i.e. 2 cycles, followed by pembrolizumab at 200mg every 3 weeks for 8 cycles along with TGR-1202 for patients with relapsed/refractory B-cell NHL or CLL. If the dose of 600mg daily of TGR-1202 (dose level 1) is tolerated in the first cohort the dose will be increased to 800mg qd which is the only and final dose escalation. If TGR-1202 is not tolerated at 600mg daily the dose will be decreased to 400mg daily. The lead in of TGR-1202 was chosen to ensure clinical benefit and to minimize the occurrence of early overlapping toxicity with pembrolizumab as most toxicities were observed early on in the treatment with idelalisib, a related PI3K-inhibitor, and rituximab.

Conditions

CLL; B-cell Non Hodgkin Lymphoma

Keywords

CLL; B-cell Non Hodgkin Lymphoma; pembrolizumab; TGR-1202

Outcome Measures

Primary Outcomes (1)

• Number of patients with adverse events

  To determine the maximally tolerated dose of TGR-1202 in combination with pembrolizumab by finding the number of patients with adverse events. This information will be used to determine the recommended phase II dose for this combination for patients with relapsed/refractory CLL/SLL and B-cell NHL.

  Up to 3 years.

Secondary Outcomes (6)

• proportion of patients with complete remission (CR)

  Up to 3 years

• duration of response (DOR)

  Up to 3 years

• progression free survival (PFS) rate

  From the start of treatment until the date of first documented progression or date of death from any cause, whichever comes first, up to 100 months

• MRD negativity rate

  Up to 3 years

• nodal response rate

  Up to 3 years

Study Arms (1)

TGR-1202 and pembrolizumab

EXPERIMENTAL

All patients will receive TGR-1202 and pembrolizumab. Patients will start receiving TGR-1202 daily for 6 weeks (2 cycles). Pembrolizumab will be given every 3 weeks for 8 cycles. If the daily dose of TGR-1202 (dose level 1) is tolerated in the first cohort the dose will be increased which is the only and final dose escalation. If TGR-1202 is not tolerated the dose will be decreased.

Drug: TGR-1202; Drug: Pembrolizumab

Interventions

TGR-1202 DRUG

TGR-1202 will be given at a dose of 600mg (dose level 1) or 800mg (dose level 2). If the dose of 600mg is tolerated in the first cohort, then the dose will be increased to 800mg which is the only and final dose escalation. If the dose of 600mg is not tolerated, then the dose will be decreased to 400mg daily.

Also known as: umbralisib

TGR-1202 and pembrolizumab

Pembrolizumab DRUG

Pembrolizumab will be given at 200 mg every 3 weeks. The dose will not be adjusted throughout the course of the study.

Also known as: Keytruda

TGR-1202 and pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent for the trial.
• Be greater than or equal to 18 years of age on day of signing informed consent.
• Have measurable disease based on iwCLL or Lugano criteria.
• Have had at least 1 prior line of standard therapy
• Be willing to provide tissue from a bone marrow biopsy if suspected involvement and/or lymph node at enrollment, as well, as a repeat bone marrow biopsy (if involved at diagnosis) after 3 of therapy and at the time of progression and/ or completion of therapy whichever comes first.
• Have a performance status of 0-1 on the ECOG Performance Scale.
• Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation.
• Hematological Absolute neutrophil count (ANC) ≥1000 /mcL Platelets ≥50,000 / mcL (if bone marrow involvement ≥30,000 mcL) Hemoglobin ≥8 g/dL
• Renal Serum creatinine OR ≤1.5 X upper limit of normal (ULN) OR Measured or calculateda ≥60 mL/min for subject with creatinine levels \> 1.5 X institutional Hepatic ULN creatinine clearance (GFR can also be used in place of creatinine or CrCl)
• Hepatic Serum total bilirubin ≤1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN AST (SGOT) and ALT (SGPT) ≤2.5 X ULN Albumin \>2.0 mg/dL
• Coagulation International Normalized ≤1.5 X ULN unless subject is receiving anticoagulant therapy as Ratio (INR) or long as PT or PTT is within therapeutic range of intended use Prothrombin Time (PT) of anticoagulants
• Activated Partial ≤1.5 X ULN unless subject is receiving anticoagulant therapy as Thromboplastin Time long as PT or PTT is within therapeutic range of intended use (aPTT) of anticoagulants
• aCreatinine clearance should be calculated per institutional standard.
• Female subject of childbearing potential should have a negative urine or serum pregnancy prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year.

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• i. Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• ii. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• \- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has a history of non-infectious pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (3)

Yale University

New Haven, Connecticut, 06520, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

umbralisib; pembrolizumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Michael Thirman, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2017
• First Posted: September 14, 2017
• Study Start: January 23, 2018
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: February 7, 2025

Record last verified: 2025-02

Locations

US (3)