Dimethylfumarate (DMF) in Relapsed/Refractory CLL/SLL
Condition: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma
MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: dimethyl fumarate
Intervention MeSH terms: Dimethyl Fumarate
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: CLL; cancer; DMF; SLL; dimethylfumarate; relapsed; refractory

Summary:

      The purpose of the study is to investigate the safety of the investigational drug called
      dimethylfumarate (DMF). DMF is a type of drug called an immunomodulatory drug. This drug is
      approved by the United States (U.S.) Food and Drug Administration (FDA) as a treatment for
      patient with multiple sclerosis.

      Although there is evidence from tests on laboratory animals that DMF can decrease the number
      of CLL cells, we do not know if this will work in humans with CLL. This drug will be given to
      humans with CLL for the first time in this study. Therefore, the goal of this study is to see
      if DMF is safe and tolerable in study participants. Participants will be evaluated to find
      out what effects (good and bad) DMF has on the body and see how long the drug stays in the
      body.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Clinical and phenotypic verification of B cell CLL/ SLL/ or MBL and measurable
             disease.

          -  Relapsed or refractory disease

          -  Previously treated with at least 1 regimen for CLL/SLL

          -  Not appropriate or amenable to all approved therapies.

               -  All patients must have progressed on or after B-cell receptor targeted kinase
                  inhibitor (eg: ibrutinib, idelalisib, ACP-196, CC-292), unless there is a
                  relative contraindication (eg: history of recent bleeding, history of atrial
                  fibrillation, unacceptable high out-of-pocket cost despite patient assistance
                  programs).

               -  Patients with Del(17p) CLL must have progressed on or after BCL-2 inhibitor
                  therapy (eg: venetoclax), unless there is a relative contraindication (eg:
                  Creatinine clearance < 50ml/min, or unable to monitor for TLS due to living
                  remotely from the medical center, unacceptably high out-of-pocket cost).

               -  Patients must have received a CD20-directed monoclonal antibody (eg:
                  obinutuzumab, ofatumumab, rituximab), unless there is a relative contraindication
                  (eg: history of hepatitis virus infection).

          -  Has recovered from the toxic effects of prior therapy to their clinical baseline.

          -  Women of childbearing potential must agree not to become pregnant for the duration of
             the study.

          -  Both men and women must agree to use a barrier method of contraception for the
             duration of the study and until 8 weeks after the final dose.

          -  Subjects must have at least one of the following indications for treatment:

               -  Symptomatic or progressive splenomegaly;

               -  Symptomatic lymph nodes, nodal clusters, or progressive lymphadenopathy;

               -  Progressive anemia;

               -  Progressive thrombocytopenia;

               -  Weight loss > 10% body weight over the preceding 6 month period;

               -  Fatigue attributable to CLL;

               -  Fever or night sweats for > 2 weeks without evidence of infection;

               -  Progressive lymphocytosis with an increase of > 50% over a 2-month period or an
                  anticipated doubling time of less than 12 months.

          -  ECOG performance status of 0-2.

          -  Adequate hematologic function

          -  Adequate renal function

          -  Adequate hepatic function

        Exclusion Criteria:

          -  Pregnant or breast-feeding women will not be entered on this study.

          -  Patients who are currently receiving another investigational agent are excluded.

          -  Patients who have had chemotherapy (e.g., purine analogues, alkylating agents),
             radiation therapy, or participation in any investigational drug treatment within 4
             weeks of initiation of DMF or at any time during the study.

          -  Patients who have had prior (within 8 weeks of initiation of DMF) or concurrent
             antibody therapy directed against CLL (i.e. Rituxan and Campath)

          -  Patients who have had tyrosine kinase inhibitor therapy (eg: ibrutinib or idelalisib)
             within 7 half lives (or 28 days, which ever is shorter) of initiation of DMF.

          -  Current infection requiring parenteral antibiotics.

          -  Active malignancy within the previous 2 years (other than completely resected
             non-melanoma skin cancer or carcinoma in situ).

          -  Insufficient recovery from surgical-related trauma or wound healing.

          -  Impaired cardiac function including any of the following:

               -  Myocardial infarction within 6 months of starting study drug;

               -  Other clinically significant heart disease