Chronic Lymphocytic LeukemiaPhase 1NCT02784834
Dimethylfumarate (DMF) in Relapsed/Refractory CLL/SLL
A Phase 1 study testing dimethyl fumarate in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Michael Choi at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
- What is being tested?
- dimethyl fumarate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2016to Feb 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
UC San Diego Moores Cancer Center
La Jolla, California, 92093
About this study
Official title: 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.
Read the 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.
- Being tested
- dimethyl fumarate
- Keywords
- CLL, cancer, DMF, SLL, dimethylfumarate, relapsed, refractory
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell, Neoplasms, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dimethyl fumarateDrug
Also called Tecfidera, DMF
| Study group | Role | What they receive |
|---|---|---|
| Dimethyl fumarate (DMF) | Experimental | 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. Receives: Drug: dimethyl fumarate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Dose Limiting Toxicity
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.
Measured: 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2016 (estimated)
- Study startJun 2016
- Primary completionFeb 2019
- Study completionFeb 2019
Why it stopped: lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Michael Choi
- Sponsor type
- University, hospital or other
- Collaborators
- The Leukemia and Lymphoma Society
- Responsible party
- Sponsor-investigator, Michael Choi, University of California, San Diego
- Investigators
- Michael Choi, MD, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02784834
- Sponsor's protocol ID
- 151657
- Status last verified
- Aug 2019
- First submitted
- 23 May 2016
- Last updated
- 19 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Clinical Trial to Evaluate Dimethylfumarate (DMF) in Relapsed/Refractory Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.
- ClinicalTrials.gov ID
- NCT02784834
- Acronym / sponsor ID
- 151657
- Keywords
- CLL, cancer, DMF, SLL, dimethylfumarate, relapsed, refractory
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: lack of funding
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Michael ChoiUniversity, hospital or other
- Collaborators
- The Leukemia and Lymphoma Society
- Study start
- Jun 2016 (actual)
- Primary completion
- Feb 2019 (actual)
- Study completion
- Feb 2019 (actual)
- First posted
- 27 May 2016 (estimated)
- Results
- Posted 19 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dimethyl fumarate (DMF) | Experimental | Drug: dimethyl fumarateCohort 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- 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.
- Has recovered from the toxic effects of prior therapy to their clinical baseline.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| dimethyl fumarateAlso: Tecfidera, DMF | Drug | Dimethyl fumarate (DMF) |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Choi, MD principal investigator
University of California, San Diego
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing dimethyl fumarate in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Michael Choi at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Dose Limiting Toxicity (time frame: 2 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2019.