Dimethylfumarate (DMF) in Relapsed/Refractory CLL/SLL

August 16, 2019 updated by: Michael Choi

Phase I Clinical Trial to Evaluate Dimethylfumarate (DMF) in Relapsed/Refractory Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

2

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • La Jolla, California, United States, 92093
        • UC San Diego Moores Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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:
  • DMF
  • Tecfidera

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
2 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Michael Choi

Collaborators

The Leukemia and Lymphoma Society

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2016

Primary Completion (Actual)

February 1, 2019

Study Completion (Actual)

February 1, 2019

Study Registration Dates

First Submitted

May 23, 2016

First Submitted That Met QC Criteria

May 24, 2016

First Posted (Estimate)

May 27, 2016

Study Record Updates

Last Update Posted (Actual)

September 19, 2019

Last Update Submitted That Met QC Criteria

August 16, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 151657

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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