Venetoclax and Romidepsin in Treating Patients With Recurrent or Refractory Mature T-Cell Lymphoma
Condition: Anaplastic Large Cell Lymphoma; Recurrent Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, Large-Cell, Anaplastic
Intervention: Laboratory Biomarker Analysis; Romidepsin; Venetoclax
Intervention description: Correlative studies; Given IV; Given PO
Intervention MeSH terms: Anti-Bacterial Agents; Venetoclax; Romidepsin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies the side effects and best dose of venetoclax and romidepsin to
      see how well it works in treating patients with mature T-cell lymphoma that has come back
      (recurrent) or does not respond to treatment (refractory). Venetoclax and romidepsin may stop
      the growth of cancer cells by blocking some of the enzymes needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Documented informed consent of the participant and/or the legally authorized
             representative

          -  Be willing to provide tissue

          -  Eastern Cooperative Oncology Group (ECOG) =< 2

          -  Resolution of all acute toxic effects of prior therapy or surgical procedures to
             Common Terminology Criteria for Adverse Events (CTCAE) grade =< 1 (except alopecia)

          -  Failed at least 2 prior systemic therapies. For anaplastic large cell lymphoma (ALCL)
             histologies this must include failure or intolerable side effects of brentuximab
             vedotin

          -  Histologically confirmed peripheral T-cell lymphoma (PTCL) as defined by the World
             Health Organization (WHO) criteria 2016, excluding cutaneous T-cell lymphoma (CTCL);
             transformed mycosis fungoides is allowed

          -  Measurable disease defined as:

               -  Computed tomography (CT)/magnetic resonance imaging (MRI)/ or positron emission
                  tomography (PET) scan, with at least one nodal site of disease which is 1.5 cm in
                  longest dimension, and/or spleen > 13 cm in vertical length, and/or diffuse
                  enlargement of liver with or without focal nodules (Lugano 2014); extra nodal
                  sites with biopsy proven abnormal lesions are allowed including skin

               -  Patients with only bone marrow involvement will be acceptable

          -  Prior stem cell transplant allowed

               -  If allogeneic hematopoietic cell transplantation (HCT) must have recovered from
                  acute toxicity

               -  Cannot have active acute or chronic graft versus host disease (GvHD) and must be
                  off immunosuppressive therapies

          -  Absolute neutrophil count (ANC) >= 1,000/mm^3 (to be performed within 14 days prior to
             day 1 of protocol therapy)

               -  NOTE: Growth factor is not permitted within 7 days of ANC assessment unless
                  cytopenia is secondary to disease involvement

               -  Exception: Unless documented bone marrow involvement by lymphoma

          -  Platelets >= 30,000/mm^3 (to be performed within 14 days prior to day 1 of protocol
             therapy)

               -  NOTE: Platelet transfusions are not permitted within 7 days of platelet
                  assessment unless cytopenia is secondary to disease involvement

               -  Exception: Unless documented bone marrow involvement by lymphoma

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN) (=< 3 x ULN for Gilbert's
             syndrome or documented hepatic involvement by lymphoma) (to be performed within 14
             days prior to day 1 of protocol therapy)

          -  Aspartate aminotransferase (AST) =< 3 x ULN (to be performed within 14 days prior to
             day 1 of protocol therapy)

               -  If hepatic involvement by lymphoma: AST =< 5 x ULN

          -  Alanine aminotransferase (ALT) =< 3 x ULN (to be performed within 14 days prior to day
             1 of protocol therapy)

               -  If hepatic involvement by lymphoma: ALT =< 5 x ULN

          -  Creatinine clearance of >= 50 mL/min per 24 hour urine or the Cockcroft-Gault formula
             (to be performed within 14 days prior to day 1 of protocol therapy)

          -  Women of childbearing potential (WOCBP): negative urine or serum pregnancy test

               -  If the urine test is positive or cannot be confirmed as negative, a serum
                  pregnancy test will be required

          -  Agreement by WOCBP and males of childbearing potential* to use an adequate method of
             birth control (hormonal contraception is inadequate) or abstain from heterosexual
             activity for the course of the study through 90 days after the last dose of protocol
             therapy

               -  Childbearing potential defined as not being surgically sterilized (men and women)
                  or have not been free from menses for > 1 year (women only)

        Exclusion Criteria:

          -  Bcl2 inhibitors

          -  Any systemic anti-lymphoma therapy, including monoclonal antibody within 28 days or 5
             half-lives (whichever is shorter) of initiating protocol therapy

          -  Radiation and/or surgery (except lymph node or other diagnostic biopsies) within 14
             days prior to day 1 of protocol therapy

          -  Short course systemic corticosteroids for disease control, improvement of performance
             status or non-cancer indication within 7 days prior to day 1 of protocol therapy;
             stable ongoing corticosteroid use (i.e. at least 30 days) up to an equivalent dose of
             20 mg of prednisone is permissible

          -  Strong or moderate CYP3A inhibitors within 7 days prior to day 1 of protocol therapy

          -  Strong or moderate CYP3A inducers within 7 days prior to day 1 of protocol therapy

          -  P-gp inhibitors within 7 days prior to day 1 of protocol therapy

          -  Narrow therapeutic index P-gp substrates within 7 days prior to day 1 of protocol
             therapy

          -  Any other investigational agent or used an investigational device within 21 days prior
             to day 1 of protocol therapy

          -  Prior surgery or gastrointestinal dysfunction that may affect drug absorption (e.g.,
             gastric bypass surgery, gastrectomy)

          -  Active human immunodeficiency virus (HIV) or hepatitis C virus (HCV) or hepatitis B
             virus (HBV); subjects who have an undetectable HIV viral load with CD4 > 200 and are
             on highly active antiretroviral therapy (HAART) medication are allowed; subjects who
             are positive for hepatitis B core antibody or hepatitis B surface antigen must have a
             negative polymerase chain reaction (PCR) result before enrollment; those who are PCR
             positive will be excluded; patients who have had hepatitis C but have finished
             treatment and are PCR negative will be allowed (testing to be done only in patients
             suspected of having infections or exposures)

          -  Concurrent malignancy requiring active therapy

          -  Known central nervous system or meningeal involvement (in the absence of symptoms,
             investigation into central nervous system involvement is not required)

          -  Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II
             to IV definitions

          -  Patients with known cardiac abnormalities such as:

               -  Congenital long QT syndrome

               -  QTc (corrected QT interval on electrocardiogram [ECG]) interval > 480
                  milliseconds

               -  Any cardiac arrhythmia requiring anti-arrhythmic medication

          -  Patients with a history of sustained ventricular tachycardia (VT), ventricular
             fibrillation (VF), Torsade de Pointes, or cardiac arrest, unless currently addressed
             with an automatic implantable cardioverter defibrillator (AICD)

          -  Active infection requiring systemic therapy

          -  Unable to swallow capsules, has a partial or small bowel obstruction, or has a
             gastrointestinal condition resulting in a malabsorptive syndrome (e.g. small bowel
             resection with malabsorption)

          -  WOCBP: Pregnant or breastfeeding

          -  Any other condition that would, in the investigator's judgment, contraindicate the
             patient's participation in the clinical study due to safety concerns with clinical
             study procedures

          -  Prospective participants who, in the opinion of the investigator, may not be able to
             comply with all study procedures (including compliance issues related to
             feasibility/logistics)