Dimethylfumarate (DMF) in Relapsed/Refractory CLL/SLL
Study Details
Study Description
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 |
|---|---|---|
|
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.
Study Design
Arms and Interventions
| 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:
|
Outcome Measures
Primary Outcome Measures
- Incidence of Dose Limiting Toxicity [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.
Eligibility Criteria
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.
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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.
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UC San Diego Moores Cancer Center | La Jolla | California | United States | 92093 |
Sponsors and Collaborators
- Michael Choi
- The Leukemia and Lymphoma Society
Investigators
- Principal Investigator: Michael Choi, MD, University of California, San Diego
Study Documents (Full-Text)
More Information
Publications
None provided.- 151657
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Dimethyl Fumarate (DMF) |
|---|---|
| Arm/Group Description | Cohort 1: dimethyl fumarate 120 mg PO BID (approximately 12 hours apart) for 2 x 28 day cycles. |
| Period Title: Overall Study | |
| STARTED | 2 |
| COMPLETED | 1 |
| NOT COMPLETED | 1 |
Baseline Characteristics
| Arm/Group Title | Dimethyl Fumarate (DMF) |
|---|---|
| Arm/Group Description | Cohort 1: dimethyl fumarate 120 mg PO BID (approximately 12 hours apart) for 2 x 28 day cycles. |
| Overall Participants | 2 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
0
0%
|
| >=65 years |
2
100%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
1
50%
|
| Male |
1
50%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
0
0%
|
| Not Hispanic or Latino |
2
100%
|
| Unknown or Not Reported |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
1
50%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
0
0%
|
| White |
1
50%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (Count of Participants) | |
| United States |
2
100%
|
Outcome Measures
| Title | Incidence of Dose Limiting Toxicity |
|---|---|
| Description | 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. |
| Time Frame | 2 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Dimethyl Fumarate (DMF) |
|---|---|
| Arm/Group Description | Cohort 1: dimethyl fumarate 120 mg PO BID (approximately 12 hours apart) for 2 x 28 day cycles. |
| Measure Participants | 2 |
| Count of Participants [Participants] |
0
0%
|
Adverse Events
| Time Frame | 4 months | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Dimethyl Fumarate (DMF) | |
| Arm/Group Description | Cohort 1: dimethyl fumarate 120 mg PO BID (approximately 12 hours apart) for 2 x 28 day cycles. | |
All Cause Mortality |
||
| Dimethyl Fumarate (DMF) | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/2 (0%) | |
Serious Adverse Events |
||
| Dimethyl Fumarate (DMF) | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/2 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| Dimethyl Fumarate (DMF) | ||
| Affected / at Risk (%) | # Events | |
| Total | 2/2 (100%) | |
| Blood and lymphatic system disorders | ||
| Lymph node pain | 1/2 (50%) | 1 |
| General disorders | ||
| Fatigue | 1/2 (50%) | 1 |
| Immune system disorders | ||
| Allergic Reaction | 1/2 (50%) | 1 |
| Investigations | ||
| Thrombocytopenia | 2/2 (100%) | 2 |
| Vascular disorders | ||
| Flushing | 2/2 (100%) | 2 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Michael Choi |
|---|---|
| Organization | UC San Diego |
| Phone | (858) 534-1765 |
| mychoi@ucsd.edu |
- 151657