Dimethylfumarate (DMF) in Relapsed/Refractory CLL/SLL

This is an interventional treatment trial for Chronic Lymphocytic Leukemia focused on measuring CLL, cancer, DMF, SLL, dimethylfumarate, relapsed, refractory Read More

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