Dimethylfumarate (DMF) in Relapsed/Refractory CLL/SLL
Ključne besede
Povzetek
Opis
This is a phase I clinical trial to evaluate the safety, tolerability, and maximum tolerated dose of DMF in patients with chronic lymphocytic leukemia. Patients with relapsed/refractory CLL not amenable to available therapies are eligible. This patient population is in need of novel therapies, particularly if progressing after, intolerant of, or unable to receive oral tyrosine kinase inhibitors (ie ibrutinib, idelalisib).
For Dose Level 1, DMF (Tecfidera formulation) will be administered at a dose of 120 mg PO BID (approximately 12 hours apart) for 2 x 28 day cycles.
For Dose Level 2, DMF will be administered at the currently used dose for patients with multiple sclerosis: at the standard FDA approved dose of 120 mg PO BID (approximately 12 hours apart) for 1 week, then escalating to the assigned dose of (240mg PO BID for the remainder of 2 x 28 day cycles. The 1 week lead-in at 120 mg is to assist in toleration and initial side effects and is as per the standard prescribing information.
For Dose Level 3, DMF will be administered at the currently used dose for patients with multiple sclerosis: 120 mg PO BID for 1 week, then escalate to the dose of 360mg PO BID for the remainder of 2 x 28 day cycles.
Datumi
| Nazadnje preverjeno: | 07/31/2019 |
| Prvič predloženo: | 05/22/2016 |
| Predviden vpis oddan: | 05/23/2016 |
| Prvič objavljeno: | 05/26/2016 |
| Zadnja posodobitev oddana: | 08/15/2019 |
| Zadnja posodobitev objavljena: | 09/18/2019 |
| Datum prvič predloženih rezultatov: | 08/15/2019 |
| Datum prve oddaje rezultatov QC: | 08/15/2019 |
| Datum prvič objavljenih rezultatov: | 09/18/2019 |
| Dejanski datum začetka študija: | 05/31/2016 |
| Predvideni datum primarnega zaključka: | 01/31/2019 |
| Predvideni datum zaključka študije: | 01/31/2019 |
Stanje ali bolezen
Intervencija / zdravljenje
Drug: Dimethyl fumarate (DMF)
Faza
Skupine rok
| Roka | Intervencija / zdravljenje |
|---|---|
| Experimental: Dimethyl fumarate (DMF) Cohort 1: dimethyl fumarate 120 mg PO BID (approximately 12 hours apart) for 2 x 28 day cycles.
Cohort 2: dimethyl fumarate 120 mg PO BID (approximately 12 hours apart) for 1 week, then escalating to the assigned dose of (240mg PO BID for the remainder of 2 x 28 day cycles.
Cohort 3: dimethyl fumarate 120 mg PO BID for 1 week, then escalate to the dose of 360mg PO BID for the remainder of 2 x 28 day cycles. | Drug: Dimethyl fumarate (DMF) |
Merila upravičenosti
| Starost, primerna za študij | 18 Years Za 18 Years |
| Spol, upravičen do študija | All |
| Sprejema zdrave prostovoljce | Da |
| Merila | 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 |
Izid
Primarni izidni ukrepi
1. Incidence of Dose Limiting Toxicity [2 months]
