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Dimethylfumarate (DMF) in Relapsed/Refractory CLL/SLL

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02784834
Recruitment Status : Terminated (lack of funding)
First Posted : May 27, 2016
Results First Posted : September 19, 2019
Last Update Posted : September 19, 2019
Sponsor:
Collaborator:
The Leukemia and Lymphoma Society
Information provided by (Responsible Party):
Michael Choi, University of California, San Diego

Brief 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.


Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Drug: dimethyl fumarate Phase 1

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Clinical Trial to Evaluate Dimethylfumarate (DMF) in Relapsed/Refractory Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.
Actual Study Start Date : June 2016
Actual Primary Completion Date : February 2019
Actual Study Completion Date : February 2019


Arm Intervention/treatment
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
Other Names:
  • Tecfidera
  • DMF




Primary Outcome Measures :
  1. Incidence of Dose Limiting Toxicity [ Time Frame: 2 months ]
    The incidence of dose limiting toxicities (DLTs) will be used to define the maximum tolerated dose or biologically active dose for potential phase 2 studies.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02784834


Locations
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United States, California
UC San Diego Moores Cancer Center
La Jolla, California, United States, 92093
Sponsors and Collaborators
Michael Choi
The Leukemia and Lymphoma Society
Investigators
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Principal Investigator: Michael Choi, MD University of California, San Diego
  Study Documents (Full-Text)

Documents provided by Michael Choi, University of California, San Diego:
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Responsible Party: Michael Choi, Associate Clinical Professor, University of California, San Diego
ClinicalTrials.gov Identifier: NCT02784834    
Other Study ID Numbers: 151657
First Posted: May 27, 2016    Key Record Dates
Results First Posted: September 19, 2019
Last Update Posted: September 19, 2019
Last Verified: August 2019
Keywords provided by Michael Choi, University of California, San Diego:
CLL
cancer
DMF
SLL
dimethylfumarate
relapsed
refractory
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Dimethyl Fumarate
Dermatologic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs