Umbralisib in Treating Patients with Relapsed or Refractory Follicular Lymphoma
This phase II trial studies how well umbralisib works in treating patients with follicular lymphoma that has come back or does not respond to treatment. Umbralisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
- Histologically proven diagnosis of grade 1, 2, or 3A FL
- The diagnosis of relapsed FL must have been made within the last 6 months of screening if no other treatment is given for the FL in the interim; if an interim treatment is given within the last 6 month, re-biopsy will be required even if there is already a biopsy proven relapsed FL within the last 6 months
- Pre-treatment biopsy must establish the diagnosis AND have enough remaining tissues to satisfy the mandatory research studies
- Relapse following first line immunotherapy or chemoimmunotherapy; there is no upper limit to the number of therapies received prior to study entry; prior therapies may include high-dose therapy with autologous stem cell rescue
- Measurable disease according to the Lugano classification
- Lymphoma that is amenable to safe pre-treatment and post-treatment biopsy; the safety of the procedures will be determined by the treating physician and the surgeon or other proceduralist, in consultation with the principal investigator (PI), and in accordance with standard clinical practice; acceptable sites of disease include, for example: (1) palpable tumor mass that is accessible under direct visualization or sonogram, (2) non-palpable tumor tissue that is accessible for biopsy under computed tomography (CT) or sonogram guidance, (3) bone marrow
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Absolute neutrophil count >= 1,000/microliter
- Platelet count >= 50,000/microliter
- Bilirubin =< 1.5 X institutional upper limit of normal
- Aspartate transaminase (AST, serum glutamic oxaloacetic transaminase [SGOT])/alanine transaminase (ALT, serum glutamic pyruvic transaminase [SGPT]) =< 3.0 X institutional upper limit of normal
- Serum creatinine =< 2.0 X institutional upper limit of normal or creatinine clearance >= 50 mL/min (according to the Cockroft and Gault equation)
- Negative serum pregnancy test within 7 days prior to cycle 1/day 1 for women of childbearing potential
- All women of childbearing potential must agree to use an effective barrier method of contraception during the treatment period and for at least 1 month after discontinuation of the study drug; male subjects should use effective barrier method of contraception during the treatment period and for at least 1 month after discontinuation of the study drug
- Ability to understand and the willingness to sign a written informed consent document
- Grade 3B FL or evidence of transformation of FL to a more aggressive lymphoma
- Prior and concomitant therapy: * Prior exposure to any PI3 kinase inhibitor * Exposure to chemotherapy, radiotherapy, or immunotherapy within 3 weeks prior to entering the study or lack of recovery from adverse events due to previously administered treatments * Ongoing chronic pharmacologic immunosuppression, e.g. cyclosporine, or systemic steroids that have not been stabilized to the equivalent of =< 10 mg/day prednisone prior to the start of the study drug * Other concurrent investigational agents during the study period
- Prior allogeneic stem cell transplant
- Central nervous system lymphoma, including lymphomatous meningitis
- Acute intercurrent illness including, but not limited to, active infection, unstable congestive heart failure, unstable angina pectoris, psychiatric illness or any social situation that would limit compliance with study participation requirements in the judgement of the investigator
- Major surgery performed within 4 weeks of study entry
- Pregnant or nursing women
- Active concurrent malignancy (except non-invasive non-melanoma skin cancer, carcinoma in situ of the cervix, or prostate intraepithelial neoplasia); if there is a history of prior malignancy, the patient must be disease-free for >= 3-years at the time of study entry
- Documented human immunodeficiency virus (HIV)-infection
- Active hepatitis A, hepatitis B, or hepatitis C infection
- History of tuberculosis treatment within 2 years of study entry
- Administration of a live vaccine within 6 weeks of first dose of study drug
- Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV), or herpes zoster (VZV) at screening
- Prior surgery or gastrointestinal dysfunction that may affect drug absorption (e.g., gastric bypass surgery, gastrectomy)
- Lymphoma that is not amenable for mandatory pre- and cycle 2 day 15 (C2D15) post-treatment biopsy
- Unstable or severe uncontrolled medical condition (e.g. unstable cardiac function, unstable pulmonary condition, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the investigator’s judgment, increase the risk to the patient associated with his or her participation in the study
- Clinically significant cardiovascular abnormalities such as: * Corrected QT interval (QTc) >= 470 msec * Angina not well-controlled by medication * Poorly controlled or clinically significant atherosclerotic vascular disease including cerebrovascular accident (CVA), transient ischemic attack (TIA), angioplasty, cardiac/vascular stenting within 6 months of enrollment * Symptomatic or documented congestive heart failure that meets New York Heart Association (NYHA) class III to IV definitions * History of stroke within the last 6 months prior to screening
Locations & Contacts
Contact: Changchun Deng
Trial Objectives and Outline
I. To determine the overall response rate (ORR) (complete remission [CR] + partial remission [PR]) in patients with relapsed or refractory (R/R) follicular lymphoma (FL).
I. Determine the genetic and other novel biological markers that are predictive of response and resistance to umbralisib (TGR-1202) in patients with relapsed or refractory FL.
II. Describe the progression free survival (PFS), duration of response (DoR) after treatment with TGR-1202.
III. Describe the number of dose delays and dose reductions.
Patients receive umbralisib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 4 weeks and then every 3 months for 1 year.
Trial Phase & Type
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Secondary IDs NCI-2017-01300
Clinicaltrials.gov ID NCT03178201