Neoplasms

All Conditions

Rare Diseases

Glioblastoma

Gliosarcoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Dermatologic Agents

Temozolomide

Dimethyl Fumarate

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

CONCOMITANT THERAPY: Between 21 days (3 weeks) and 42 days (6 weeks) following the last surgical procedure, patients receive temozolomide PO QD for 42-49 days and dimethyl fumarate PO BID or TID continuously. Patients also undergo radiation therapy 5 days a week over 6 weeks for a total of 30 fractions

MAINTENANCE THERAPY: Patients continue to receive dimethyl fumarate PO BID or TID continuously. Four weeks after completing concomitant temozolomide and radiation therapy, patients also receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Radiation Therapy

Mark G Malkin, MD

This phase 1 trial studies the side effects and best dose of dimethyl fumarate when given together with temozolomide and radiation therapy(RT) in treating patients with newly diagnosed glioblastoma multiforme (GBM). Dimethyl fumarate may help radiation therapy work better by making tumor cells more sensitive to the radiation therapy. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving dimethyl fumarate with temozolomide and radiation therapy may work better in treating glioblastoma multiforme.

PRIMARY OBJECTIVES:

I. To determine the recommended phase 2 dose (RP2D) of dimethyl fumarate (DMF) when combined with standard concurrent temozolomide and RT in subjects with newly diagnosed glioblastoma multiforme (GBM).

SECONDARY OBJECTIVES:

I. To evaluate the safety, tolerance, and toxicity of DMF when combined with standard concurrent temozolomide and RT in subjects with newly diagnosed GBM.

II. To obtain a preliminary estimate of the efficacy of DMF when combined with standard concurrent temozolomide and RT in subjects with newly diagnosed GBM.

OUTLINE: This is a dose-escalation study of dimethyl fumarate.

CONCOMITANT THERAPY: Between 21 days (3 weeks) and 42 days (6 weeks) following the last surgical procedure, patients receive temozolomide orally (PO) once daily (QD) for 42-49 days and dimethyl fumarate PO twice daily (BID) or thrice daily (TID) continuously. Patients also undergo radiation therapy 5 days a week over 6 weeks for a total of 30 fractions.

MAINTENANCE THERAPY: Patients continue to receive dimethyl fumarate PO BID or TID continuously. Four weeks after completing concomitant temozolomide and radiation therapy, patients also receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days and then every 2 months thereafter.

Dimethyl Fumarate, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

Phase I Trial of Dimethyl Fumarate, Temozolomide, and Radiation Therapy in Glioblastoma Multiforme

Subjects' treatment dosing level, dose modification, DLTs, and evaluability for DLTs and response will be listed and summarized by basic descriptive statistics (such as frequency and proportion).

Subjects' demographics, adverse events, serious adverse events, and treatment status will be listed and summarized by descriptive statistics (such as frequency, proportion, mean, standard deviation, median, and range).

The Kaplan-Meier method will be conducted to describe PFS, and median PFS will be estimated, along with 95% confidence intervals. A Cox regression model may be used to model the PFS and adjusting for any effects of potential clinical characteristics.

The Kaplan-Meier method will be conducted to describe OS, and median OS will be estimated, along with 95% confidence intervals. A Cox regression model may be used to model the OS and adjusting for any effects of potential clinical characteristics.

The clinical response rate will be calculated for each cohort, along with their corresponding 95% confidence intervals. Logistic regression may be used to model the rate by adjusting potential clinical characteristics (such as age, gender, and tumor grade). Mean and standard deviation of duration of response (overall response, complete response, and stable disease, respectively), along with its 95% confidence interval, will be estimated based on the method proposed by Ellis et al. via the exponential distribution.

National Cancer Institute (NCI)

Virginia Commonwealth University

Blood and Lymph Conditions

Immune System Diseases

Lymphoma

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Lymphoma, T-Cell, Cutaneous

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Peripheral T-cell Lymphoma

Cutaneous T-cell Lymphoma

patients are treated with dimethylfumarate over 24 weeks. Dosage will be escalated weekly from 30 mg/d to 720 mg/d over 9 weeks. The dose escalation scheme is the same as approved for psoriasis treatment in Germany

dose escalation from 30 mg/d to maximally 720 mg/d over 9 weeks, then continuing with the highest tolerated dose following a preset design in psoriasis treatment in Germany, oral medication in tablet form. Treatment will last 24 weeks or until either progression or unacceptable side effects occur

Dimethyl fumarate

The main objective of the trial is to investigate whether oral treatment of patients suffering from cutaneous T cell lymphoma with dimethylfumarate is leading to a significant improvement of modified severity assessment tool (mSWAT) values in the skin after 24 weeks of treatment (primary endpoint). Secondary endpoints are dermatologic life quality index, itching and pain measured by a NRS and the blood involvement if applicable.

Primary: safety and efficacy of DMF treatment in CTCL Secondary: Dermatologic Life Quality index, NRS for itching and pain, blood involvement if appl.

Study on Therapy With Dimethylfumarate (DMF) in Patients With Cutaneous T Cell Lymphoma (CTCL)

Phase IIA Study on Therapy With the NF-κB Inhibiting and Apoptosis Inducing Drug Dimethylfumarate (DMF) in Patients With Cutaneous T Cell Lymphoma (CTCL)

Number of patients with Treatment-related Adverse Events as assessed by CTCAE v4.0

Changes in the mSWAT scores range from 0 \[no patches, Plaques or tumors on the Skin \] to 400 \[complete Body covered by Tumors\]

Scores range from 0 \[no restriction of life Quality\] to 30 \[maximal restriction of life Quality\]

Scores range from 0 \[no Pruritus\] to 10 \[worst possible Pruritus\]

Klinikum Minden

Klinikum Krefeld

Wuerzburg University Hospital

KKS Netzwerk

Klinikum Ludwigshafen

Universitätsklinikum Kiel

Universitätsmedizin Mannheim

MD MSc

Symptoms and General Pathology

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Hematologic Diseases

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

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.

dimethyl fumarate

Michael Choi, MD

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.

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.

Dimethylfumarate (DMF) in Relapsed/Refractory CLL/SLL

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

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.

The Leukemia and Lymphoma Society

Michael Choi

Associate Clinical Professor

Cohort 1: dimethyl fumarate 120 mg PO BID (approximately 12 hours apart) for 2 x 28 day cycles.

Dimethyl Fumarate (DMF)

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Michael Choi

Incidence of Dose Limiting Toxicity

Overall Study

Nervous System Diseases

Neoplasm Metastasis

Sclerosis

Multiple Sclerosis

Multiple Sclerosis, Chronic Progressive

Disease Progression

Autoimmune Diseases

Demyelinating Autoimmune Diseases, CNS

Autoimmune Diseases of the Nervous System

Demyelinating Diseases

Neoplastic Processes

BG00012 120 mg (1 BG00012 120 mg capsule + 1 matching placebo capsule) orally twice daily (BID) for 1 week, followed by BG00012 240 mg orally BID thereafter.

BG00012 120 mg capsule orally once a day supplemented with matching placebo capsules for the first 4 weeks of treatment, as an additional blinding measure. Matched placebo capsules only thereafter.

Placebo

Medical Director

The primary objective of the study is to investigate whether treatment with BG00012 (dimethyl fumarate) compared with placebo slows the accumulation of disability not related to relapses in participants with secondary progressive multiple sclerosis (SPMS). The secondary objective of the study is to assess the effect of BG00012 compared with placebo on patient-reported outcomes, brain atrophy, and cognitive function.

BG00012 and Delay of Disability Progression in Secondary Progressive Multiple Sclerosis

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of BG00012 in Delaying Disability Progression in Subjects With Secondary Progressive Multiple Sclerosis

Time to onset of confirmed progression of disability is defined as 1 or more of the following criteria, confirmed at ≥ 6 months after start of treatment and at Week 108 using 1 or more of the following assessments: Expanded Disability Status Scale (EDSS) score increased from Baseline of ≥ 1 point if baseline EDSS ≤ 5.5, or ≥ 0.5 point if Baseline EDSS ≥ 6.0; Timed 25-Foot Walk (T25FW) ≥ 20% increase from Baseline in the time taken for the 25-foot walk; worsening on the 9-Hole Peg Test (9HPT; ≥ 20% increase from Baseline in the time taken for the 9HPT, confirmed in the same hand). The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. The T25FW is a quantitative mobility and leg function performance test where the participant is timed while walking for 25 feet. The 9HPT is a quantitative test of upper extremity function that measures the time it takes to place 9 pegs into 9 holes and then remove the pegs.

MSWS-12 is a participant self-assessment of walking limitations due to multiple sclerosis (MS) during the past 2 weeks. It contains 12 items that measure the impact of MS on walking. Items are summed to generate a total score and transformed to a scale with a range of 0 to 100, where high scores indicate greater negative impact on walking.

The ABILHAND Questionnaire measures the participant's perceived difficulty in performing everyday manual activities in the last 3 months. Participants fill in the 56-item questionnaire by estimating their own difficulty or ease in performing each of the 56 activities. Items are summed to generate a total score and transformed to a scale with a range of 0 to 100, where high scores indicate greater impact on manual ability.

Whole brain volume is measured by magnetic resonance imaging (MRI).

The SDMT measures the time to pair abstract geometric symbols with specific numbers. The score is the number of correctly coded items from 0-110 in 90 seconds. A higher score indicates a better outcome.

Biogen

Data summaries of adverse events are descriptive in nature and the comparison between treatment groups might not be appropriate due to the small number of participants and limited study follow-up duration.

BG00012 120 mg capsule orally QD supplemented with matching placebo capsules for the first 4 weeks of treatment. Matched placebo capsules only thereafter for up to 108 weeks.

BG00012 120 mg orally BID for 1 week, followed by BG00012 240 mg orally BID beginning on Day 8 for up to 108 weeks.

Tecfidera 240 mg BID

Total

Age, Continuous

< 20 years

20 to 29 years

30 to 39 years

40 to 49 years

>= 50 years

Age, Customized

The study was terminated early by the sponsor for business reasons. Efficacy, patient-reported outcomes, and pharmacodynamic data were not analyzed.

Biogen Study Medical Director

BG00012 120 mg capsule orally once a day (QD) supplemented with matching placebo capsules for the first 4 weeks of treatment. Matched placebo capsules only thereafter for up to 108 weeks.

BG00012 120 mg orally twice daily (BID) for 1 week, followed by BG00012 240 mg orally BID beginning on Day 8 for up to 108 weeks.

The limited number of participants enrolled and the early termination of the study resulted in efficacy data not collected, and efficacy outcomes not analyzed, as per the pre-specified plan of analysis.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Dimethyl Fumarate, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme	NCT02337426	Adult Brain Gli... Adult Giant Cel... Adult Gliosarco...	Dimethyl Fumara... Temozolomide Radiation Thera...	18 Years -	Virginia Commonwealth University
Study on Therapy With Dimethylfumarate (DMF) in Patients With Cutaneous T Cell Lymphoma (CTCL)	NCT02546440	Cutaneous T Cel...	Dimethyl fumara...	18 Years -	Universitätsmedizin Mannheim
Study on Therapy With Dimethylfumarate (DMF) in Patients With Cutaneous T Cell Lymphoma (CTCL)	NCT02546440	Cutaneous T Cel...	Dimethyl fumara...	18 Years -	Universitätsmedizin Mannheim
Study on Therapy With Dimethylfumarate (DMF) in Patients With Cutaneous T Cell Lymphoma (CTCL)	NCT02546440	Cutaneous T Cel...	Dimethyl fumara...	18 Years -	Universitätsmedizin Mannheim
Dimethylfumarate (DMF) in Relapsed/Refractory CLL/SLL	NCT02784834	Chronic Lymphoc... Small Lymphocyt...	dimethyl fumara...	18 Years -	University of California, San Diego
BG00012 and Delay of Disability Progression in Secondary Progressive Multiple Sclerosis	NCT02430532	Multiple Sclero...	dimethyl fumara... Placebo	18 Years - 58 Years	Biogen

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