Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

Infections

Rare Diseases

Syndrome

Lymphoma

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Mycoses

Mycosis Fungoides

Lymphoma, T-Cell, Cutaneous

Sezary Syndrome

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Communicable Diseases

Bacterial Infections

Bacterial Infections and Mycoses

Lymphoma, Non-Hodgkin

Lymphosarcoma

Peripheral T-cell Lymphoma

Cutaneous T-cell Lymphoma

3 x 200 mg tablets p.o., 5 days treatment followed by 9 days rest (cycles until progress or unacceptable toxicity)

3 tablets p.o. matching verum, 5 days treatment followed by 9 days rest (cycles until progress or unacceptable toxicity)

resminostat

Placebo

Rudolf Stadler, Prof.

The purpose of this study is to determine whether resminostat will be able to delay or prevent worsening of disease in patients with advanced stage mycosis fungoides or Sézary Syndrome that have recently achieved disease control with previous systemic therapy.

Resminostat for Maintenance Treatment of Patients With Advanced Stage Mycosis Fungoides (MF) or Sézary Syndrome (SS)

A Multicentre, Double Blind, Randomised, Placebo-controlled, Phase II Trial to Evaluate Resminostat for Maintenance Treatment of Patients With Advanced Stage (Stage IIB-IVB) Mycosis Fungoides (MF) or Sézary Syndrome (SS) That Have Achieved Disease Control With Systemic Therapy - the RESMAIN Study

Compare time to progression (TTP) in patients when treated with resminostat vs placebo

Compare time to next treatment (TTNT) in patients when treated with resminostat vs placebo

Assess the effect of maintenance treatment with resminostat by means of PFS of subsequent treatments (PFS2, PFS3)

Compare overall response rate (ORR, including CR, PR) in patients when treated with resminostat vs placebo

Compare duration of response (DOR) in patients when treated with resminostat vs placebo

Compare overall survival (OS) in patients when treated with resminostat vs placebo

Assess the safety and tolerability of resminostat

Compare changes in health related quality of life (HrQoL) parameters in patients when treated with resminostat vs placebo

Assess the maximum plasma concentration \[Cmax\] of resminostat and metabolites

Assess the Area Under the Curve \[AUC\] of resminostat and metabolites

The primary objective is to determine if maintenance treatment with resminostat increases progression free survival (PFS) compared to placebo in patients with advanced stage (Stage IIB-IVB) MF or SS that have achieved disease control (complete response \[CR\], partial response \[PR\] or stable disease \[SD\]) with previous systemic therapy.

To determine if maintenance treatment with resminostat increases time to symptom (pruritus) worsening (TTSW) compared to placebo.

4SC AG

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Immunoglobulins

Brentuximab Vedotin

Antineoplastic Agents, Immunological

Immunotoxins

Immunoconjugates

Immunologic Factors

(Eligible patients with Stage IB, IIA, IIB, and IIIA \[if N0-1\])

Brentuximab Vedotin 1.8 mg/kg IV every 3 weeks for 3 doses beginning 3 weeks prior to initiation of TSEB.

TSEB 12 Gy in 6 fractions at 2 Gy/fraction treated twice/week.

(Eligible patients with Stage IIA, IIB, IIIA \[if N2-3\]; IIIB; Stage IVA; and transformed CTCL)

Brentuximab Vedotin 1.8 mg/kg IV every 3 weeks for 3 doses beginning 3 weeks prior to initiation of TSEB.

TSEB 12 Gy in 6 fractions at 2 Gy/fraction treated twice/week.

Continuation of brentuximab every 3 weeks until disease progression or unacceptable toxicity or for up to 2 years as a study participant, (whichever occurs first).

TSEB is a type of radiation treatment in which the skin over the whole body is treated with electron radiation beams. All participants will receive the same standard TSEB dose and treatment schedule. During TSEB, patients are treated in a standing position on a rotating platform.

TSEB Therapy

An antibody-drug conjugate (ADC) that targets CD30. A standard dose of brentuximab vedotin will be administered to all patients by intravenous infusion 3 weeks prior to initiation of TSEB and then every 3 weeks for 3 cycles.

Brentuximab vedotin

Shiyu Song, M.D., Ph.D.

The purpose of this study is to evaluate the cutaneous toxicity and treatment response associated with administering concurrent TSEB and brentuximab vedotin in patients with mycosis fungoides or Sézary Syndrome.

This study is a 2-cohort, open-label, phase 1B trial to evaluate the cutaneous toxicity, overall toxicity, and treatment response associated with administering concurrent low-dose TSEB and brentuximab vedotin in patients with mycosis fungoides or Sézary Syndrome. Duration of complete skin response, DOCB, and tumor response in lymph nodes and blood will also be evaluated. Additionally, skin-related QOL and neurotoxicity will be assessed.

Patients will be enrolled in 1 of 2 cohorts based on disease stage.

Cohort A will include patients with earlier stage disease (selected Stage IB in patients who have had one previous course of therapy) and Stages IIA through IIIA \[if N0-1\]).

Cohort B will include patients with more advanced disease (Stage IIA through IIIA \[if N2-3\], Stage IIIB, Stage IVA, and transformed CTCL) who are candidates for low-dose TSEB and/or systemic therapy.

A standard dose of brentuximab vedotin will be administered to all patients by intravenous infusion 3 weeks prior to initiation of low-dose TSEB and then every 3 weeks for a total of 3 cycles. Cohort A patients will complete brentuximab vedotin after 3 cycles; patients in Cohort B will continue brentuximab vedotin until disease progression or unacceptable toxicity, whichever occurs first. In the absence of progression or unacceptable toxicity, the patient may receive brentuximab vedotin for up to 2 years as a study participant. A total of 12 Gy TSEB (ie, low-dose TSEB) will be administered to both cohorts per standard protocol in 6 fractions (2 fractions per week) beginning 3 weeks after the first dose of brentuximab vedotin.

The Modified Severity Weighted Assessment Tool (mSWAT) (16), completed by the investigator, will be used to determine skin involvement at baseline and skin response to treatment beginning after administration of the 3 doses of brentuximab vedotin and low-dose TSEB. Skindex-16, a patient-completed form that measures symptoms and perceptions of toxicity in patients with skin disease will be used to assess skin-related QOL. Additionally, Form NTX will be completed by patients in Cohort A to assess symptoms of CIPN which is a side effect of brentuximab vedotin.

The sample size for this study will be a maximum of 15 patients for a total of 12 evaluable patients with no more than 6 patients in Cohort B. However, if the number of patients with severe toxicity exceeds the established acceptable incidence, accrual will end before reaching the sample size goal of 12 evaluable patients.

TSEB and Brentuximab for Treatment of Mycosis Fungoides & Sezary Syndrome

Phase 1B Trial: Evaluation of the Safety of Adding Brentuximab Vedotin to Low-Dose Total Skin Electron Beam (TSEB) for Treatment of Patients With Mycosis Fungoides and Sézary Syndrome

Selected cutaneous adverse events (AEs) that occurred during treatment or during the 3 months following initiation of study treatment and that are characterized and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI CTCAE v4.0) including ≥ grade 3 AEs and selected grade 2 AEs

Number of patients who have achieved cutaneous CR to treatment defined as 100% clearance of skin lesions or cutaneous partial response (PR) defined as 50%-99% clearance of skin disease from baseline without new tumors in patients with T1-, T2-, or T4-only skin disease.

Duration of skin response defined as the time from first determination of CR until relapse in the skin based on mSWAT assessment.

Tumor response in lymph nodes for patients with N2 or N3 disease at baseline.

Tumor response in blood for patients with B1 or B2 disease at baseline.

AEs reported using criteria in the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) and AEs defined in the protocol.

Patient responses to questions on Skindex-16 (standardized assessment measures for patients with skin disease) that will be administered at baseline and at 2, 4, 10, and 16 weeks following completion of TSEB

Patient responses to questions on Form NTX (standardized patient-completed assessment tool to evaluate CIPN) that will be administered at baseline and at 2, 4, 10, and 16 weeks following completion of TSEB.

DOCB defined as the time from initial response until any total skin-equivalent treatment (eg, topical treatment to \> 50% of body surface, phototherapy, second TSEB treatment) or systemic therapy is initiated, or until disease progression.

Seagen Inc.

Virginia Commonwealth University

Panobinostat

Histone Deacetylase Inhibitors

Enzyme Inhibitors

Participants received panobinostat, 20 milligrams (mg), capsules, orally, thrice weekly on alternate Days 1, 3, and 5 per week of a 28-day treatment cycle until unacceptable toxicity, disease progression, and/or physician's discretion to discontinue the treatment.

Panobinostat, 20 mg, hard gelatin capsules, orally, thrice weekly.

Novartis Pharmaceuticals

This study evaluated the safety and efficacy of LBH589B in adult participants with refractory/resistant Cutaneous T-Cell Lymphoma and prior Histone Deacetylase (HDAC) inhibitor therapy.

Study of Oral LBH589 in Adult Participants With Refractory/Resistant Cutaneous T-Cell Lymphoma (CTCL)

A Phase II Study of Oral LBH589 in Adult Patients With Cutaneous T-Cell Lymphoma Who Are Intolerant to or Have Progressed on or After Prior HDAC Inhibitor

ORR was defined as the percentage of participants with best overall response (OR) of complete response (CR) or partial response (PR) based on mSWAT score, (OR = CR + PR). mSWAT score represents the product of the percentage total body surface area (%TBSA) involvement of each lesion type (patch, plaque, and tumor or ulceration), multiplied by a weighting factor: modified SWAT score = (patch %TBSA x 1) + (plaque %TBSA x 2) + (tumor or ulcer %TBSA x 4). The sum of these 3 numbers gave the modified SWAT score, on a 0 (no lesions) to 400 (lesions covering all areas) scale. CR based on mSWAT score was defined as the absence of skin disease. PR was defined as ≥ 50% decrease of the modified SWAT score compared to the Baseline score.

Response rate was defined as the percentage of participants with CR or PR based on PGA scale. PGA is a 7-point grading scale for the investigator's assessment of the overall extent of improvement or worsening of the participant's disease as compared to Baseline. CR corresponds to Grade 0 (Completely clear) on PGA scale and was defined as no evidence of disease; 100% improvement. PR corresponds to Grade 2 (marked improvement) on PGA scale and was defined as significant improvement (≥75% - \<90%); some evidence of disease remains.

Response rate was defined as the percentage of participants with CR or PR based on mSWAT skin score. mSWAT score represents the product of the %TBSA involvement of each lesion type (patch, plaque, and tumor or ulceration), multiplied by a weighting factor: mSWAT score = (patch %TBSA x 1) + (plaque %TBSA x 2) + (tumor or ulcer %TBSA x 4). The sum of these 3 numbers gave the modified SWAT score, on a 0 (no lesions) to 400 (lesions covering all areas) scale. CR based on mSWAT score was defined as the absence of skin disease. PR was defined as ≥ 50% decrease of the modified SWAT score compared to the Baseline score.

Index lesions in each participant were selected as four to six of the prominent lesions amenable to bi-dimensional measurements. The longest diameter and its perpendicular measurement were used to determine the surface area and a weighted sum was determined as: Lesion 1 + lesion 2 + ... + lesions 6 = Total sum of weighted score where Lesion 1: cm\^2 x \[1 (for patch); 2 (for plaque); 4 (for tumor or ulcer)\]; Lesion 2: cm\^2 x \[1 (for patch); 2 (for plaque); 4 (for tumor or ulcer)\]; Lesion 6: cm\^2 x \[1 (for patch); 2 (for plaque); 4 (for tumor or ulcer)\]. These lesions were photographed at Baseline and at the time of response determined by either mSWAT or PGA

ORR was defined as the percentage of participants with best OR of CR or PR based on PGA scale (OR = CR + PR). The PGA is a 7-point grading scale for the investigator's assessment of the overall extent of improvement or worsening of the participant's disease as compared to Baseline. CR corresponds to Grade 0 (completely clear) of PGA scale and was defined as no evidence of disease; 100% improvement. PR corresponds to Grade 2 (marked improvement) of PGA scale and was defined as significant improvement (≥75%-\<90%); some evidence of disease remains.

DOR was defined as the time from first documented evidence of CR or PR until the earliest date of documented progression or death due to any cause among participants who achieved a confirmed CR or PR. The DOR was calculated in two ways. The DOR among responders only included participants who responded to the drug. The overall DOR included non-responders as having a DOR of zero days.

TTR was defined as the time from the start of treatment until the first documented evidence of CR or PR among participants who achieved a confirmed CR or PR.

PFS was defined as the time from the start of treatment until the earliest date of disease progression or death due to any cause, if sooner.

Safety population included all participants who received at least one dose of study drug and had at least one valid post-baseline assessment.

Participants received panobinostat, 20 mg, capsules, orally, thrice weekly on alternate Days 1, 3 and 5 per week of a 28-day treatment cycle until unacceptable toxicity, disease progression and/or physician's discretion to discontinue the treatment.

Panobinostat 20 mg

Age, Continuous

Sex: Female, Male

Full Analyses Set (FAS) population was defined according to the Intention-to-Treat (ITT) principle and included all participants enrolled into the study.

The study was terminated early due to low accrual, no formal efficacy analyses were conducted for this study.

Study Director

Since the study was terminated early due to low prevalence of study population and slow accrual Since the study was terminated early due to low accrual, no analyses were conducted for this study.

Overall Response Rate (ORR) in Participants With Resistant Cutaneous T-Cell Lymphoma (CTCL) Treated With Oral Panobinostat by Using the Modified Severity-Weighted Assessment Tool (mSWAT)

Response Rate of Participants With Refractory CTCL Using the Physician's Global Assessment of Clinical Condition (PGA)

Response Rate in Participants With Refractory CTCL Using Modified Skin Score

Responses in Index Lesions in Participants With Refractory CTCL by Lesion Measurements With Photographic Supporting Documentation

ORR of Participants With Resistant CTCL Treated With Oral Panobinostat by Using the Modified PGA to Assess Skin Disease and the Evaluation of Disease in the Viscera, Lymph Nodes and Blood (Circulating Sézary Syndrome Cells)

Duration of Response (DOR)

Time to Response (TTR)

Progression-Free Survival (PFS)

Overall Study

Skin and Connective Tissue Diseases

Pruritus

Skin Diseases

Skin Manifestations

Narcotic Antagonists

Analgesics

Central Nervous System Depressants

Naloxone

Opiate Alkaloids

Narcotics

Naloxone Hydrochloride Lotion, 0.5%

Placebo Lotion

Scott B Phillips, MD

This multi-center, double-blind, vehicle-controlled, randomized crossover design study will evaluate the safety and efficacy of topically applied naloxone lotion, 0.5%, for the treatment of pruritus in patients with the mycosis fungoides (MF) or Sézary syndrome (SS) Forms of Cutaneous T-cell Lymphoma (CTCL). This study will also determine if there is systemic absorption of the drug in a subset of subjects and if so, describe the range and mean plasma levels reached after two weeks of three time daily (TID) dosing.

Funding Source - FDA OOPD

There will be 160 subjects enrolled in the study. The study consists of a Screening Period of up to 7 days during which inclusion / exclusion criteria will be reviewed. Subjects meeting inclusion / exclusion criteria including the diagnostic criteria for MF or SS and a score of at least 5 on the 11-Point Numeric Rating Scale (NRS) for Pruritus will complete the one week Screening Period. Subjects will complete a daily diary for NRS for Pruritus scores and Sleep scores. At the end of the Screening Period, subjects who have a NRS for Pruritus score of at least 5 recorded in the diary on at least 4 of the 7 days preceding Day 0 will be eligible to continue. Baseline assessments will be recorded for vital signs, pruritic body surface area, skin integrity, PQOL, and laboratory results. The Baseline period will be followed by a 2 week Treatment Period 1 in which subjects will be randomized to Naloxone Lotion 0.5% or Placebo Lotion to be applied TID for 14 days. During the 2 week Treatment Period subjects will complete daily diaries of NRS for Pruritis scores and Sleep scores. On Day 14 subjects will return to the clinic to review diaries, adverse events (AEs), concomitant medications, and to record body surface area for pruritus, skin integrity, PQOL, and laboratory results. Subjects will then enter a Washout Period for up to 56 days until the subject again scores at least 5 on the NRS for Pruritus on 4 consecutive or 4 of the past 7 days or 56 days pass. Subjects will then enter a 2 week Treatment Period 2 during which the same procedures as Treatment Period 1 will be performed except subjects will receive the alternate treatment to that assigned in Treatment Period 1. Subjects will then have the option to enter a 26 Week Open Label Treatment Period 3 during which the same procedures as Treatment Period 1 and 2 will be performed except subjects will return only at Week 13 and Week 26 and all subjects will be treated with Naloxone Lotion 0.5%.

Naloxone Hydrochloride Study for Relief of Pruritus in Patients With MF or SS Forms of CTCL

A Double Blind Randomized Vehicle Controlled Crossover Study to Evaluate the Safety and Efficacy of Topical Naloxone Hydrochloride Lotion 0.5% for the Relief of Pruritus in Patients With the MF or SS Forms of Cutaneous T-Cell Lymphoma

Change from Baseline to Day 14 in average NRS for Pruritus for each Treatment Period

The difference in the proportion of subjects with a meaningful clinically significant improvement at the end of the two periods. A clinically significant improvement is defined as an improvement of at least one category on the 4-point (none, mild, moderate, severe) Likert Scale verbal rating scale (VRS) and at least two points on the 11-point NRS for Pruritus. The NRS for Pruritus scores will be converted to VRS scores as follows for the analysis: 0=none, 1-3=mild, 4-6=moderate, and 7-10=severe.

The change from Baseline at each week of the NRS for Sleep average score for each Treatment Period.

The change from Baseline at Week 1 of the NRS for Pruritus average score for each Treatment Period.

The change from Baseline at Week 2 of the CRS for Skin Integrity for each Treatment Period.

The change from Baseline in the final categorization of the PQOL at Day 14 of each Treatment Period

Elorac, Inc.

Anti-Inflammatory Agents

Antirheumatic Agents

Herbal and Botanical

Turmeric extract

Curcumin

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Antioxidants

Protective Agents

Turmeric

Chew then swallow 2 sticks per day for up to 6 months.

2 sticks = 1 packet of curcumin = 8 grams

Curcumin (Turmeric)

Quality of life (QOL) questionnaires completed on Day 1, Weeks 2, 4, 8, 12, 16, 20, and at end of treatment visit.

Questionnaires

Photos of up to 6 selected skin lesion(s) and half-body photos taken on Day 1, Weeks 2, 4, 12, and at end of treatment visit.

Photos

Madeleine Duvic, MD

The goal of this clinical research study is to learn if treatment with curcumin can help to decrease the size of lesions and/or decrease itching in patients with MF or SS. The safety of curcumin will also be studied.

Curcumin:

Curcumin, a yellow substance taken from a plant, is commonly used in cooking as a spice called turmeric. In this study, participants will receive much higher doses of curcumin than can be received through food.

Curcumin may block proteins that help cells to divide. These proteins also may stop cancer cells from dying.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will swallow 2 sticks of curcumin per day. You should take the 2 sticks each morning with food and enough water for you to be able to swallow them. If you miss taking a dose of curcumin in the morning, you can take it later that day (as soon as you remember). However, if you miss a dose all day, do not take 2 doses the next day to make up for it.

Study Visits:

You will be asked to return for study visits.

At "baseline" (Day 1), the following tests and procedures will be performed:

* You will have a physical exam, including measurement of your vital signs.
* You will be asked to rate your itching on a scale of 0-10.
* You will complete the 2 quality-of-life questionnaires.
* The study staff will take photos of up to 6 selected skin lesion(s). These will be close-up photos of the lesions and a small area of surrounding skin. "Half-body" photos will also be taken. These will be front, back, and/or side views of the top and bottom half of your body, depending on where the lesions are. For the half-body photos, your private areas will be covered (as much as possible), and your face will not be included in the photos unless there are lesions there.
* Blood (about 3 teaspoons) will be drawn for routine tests
* You will complete 2 "quality-of-life" questionnaires that ask how the symptoms of the disease may be affecting your life. This should take about 5 minutes.
* You will have a physical exam, including having skin lesions and affected areas of your skin looked at by the study doctor.
* If the study doctor thinks it is needed, you will have a skin biopsy performed. To perform a skin biopsy, the area is numbed with anesthetic and a small amount of tissue (about the size of a pencil eraser) is removed with a special tool.

The following tests and procedures will be performed at Weeks 2, 4, 8, 12, 16, and 20:

* You will have a physical exam, including having skin lesions and affected areas of your skin looked at by the study doctor.
* You will complete the 2 quality-of-life questionnaires.
* Your vital signs will be measured.
* You will be asked to rate your itching on a scale of 0-10.

At Weeks 2, 4, and 12 only, the following additional test will be performed:

-Just like at baseline, you will have skin lesion photos and half-body photos taken.

At Weeks 4, 12, and 20 only, the following additional test will be performed:

-Blood (about 3 teaspoons) will be drawn for routine tests.

If the doctor decides it is needed based on abnormal blood tests at screening, additional blood (about 1 teaspoon) will be drawn to check the status of the disease at Weeks 2, 4, 8, and 12.

If at any time during the study the skin disease seems to have cleared, you will have a skin biopsy performed in order to confirm the response.

Length of Study Participation:

You may continue receiving the study drug for up to 6 months, as long as you and the study doctor think you are benefitting from taking curcumin. If the disease gets worse or intolerable side effects occur at any time during this study, you will be taken off study.

End-of-Treatment Visit:

When you go off study for any reason, you will have an end-of-treatment visit. The following procedures will be performed:

* You will have a physical exam.
* You will be asked to rate your itching on a scale of 0-10.
* Blood (about 2 teaspoons) will be drawn for routine tests.
* If the doctor decides it is needed based on abnormal blood tests at screening, additional blood (about 1 teaspoon) will be drawn to check the status of the disease.
* A skin biopsy will be performed to check the status of the disease.
* Photos of the skin lesion(s) will be taken.
* You will complete the 2 quality-of-life questionnaires.
* You will have a CT and/or PET scan to check the size of the lymph nodes.

Follow-Up:

Every 3 months for 6 months after your last dose of the study drug, the study staff will check the results of any routine tests that were performed at your regular follow-up visits for MF or SS. If you do not visit the clinic during one or both of these two 3-month time periods, you will be called at home at 3 months and/or 6 months after your last dose of the study drug. The purpose of the phone calls is to ask how you are doing.

This is an investigational study. Curcumin is not FDA approved or commercially available for the treatment of cutaneous T-cell lymphoma. For this purpose, it is being used in research only.

Up to 20 patients will take part in this study. All will be enrolled at M. D. Anderson.

Trial of Curcumin in Cutaneous T-cell Lymphoma Patients

Phase II Trial of Curcumin in Cutaneous T-cell Lymphoma Patients

M.D. Anderson Cancer Center

Interleukin-12

Adjuvants, Immunologic

Angiogenesis Inhibitors

Growth Inhibitors

The LD-TSEBT treatment will start on Day 1 of the study. NM-IL-12 will be administered subcutaneously.

NM-IL-12 and TSEBT

Youn H Kim, MD

In the proposed study, NM-IL-12 will be evaluated as immunotherapy to increase antitumor efficacy against CTCL, while reducing skin-related toxicity, when combined with low-dose TSEBT therapy. Determination of the maximum tolerated dose (MTD) for NM-IL-12 is not planned in this study, rather, a pre-defined starting dose will be explored; this dose is based on two safety and tolerability studies of NM-IL-12 in healthy volunteers.

This is a single arm, open-label, non-randomized study with NM-IL-12 dosed in combination with low dose TSEBT in CTCL patients. This study is planned to be conducted in 10 patients, 18 years or older in age, undergoing low dose TSEBT of 12 Gy over a 3-week period.

The study will initially enroll 4 patients and then will be expanded to enroll 6 additional patients (total 10 patients) depending on the presence or absence of Dose Modifying Criteria (DMC). Decision whether to de-escalate will be made after first 4 patients are followed up for 28 days from the first dose of NM-IL-12.

Safety monitoring will continue throughout the whole period of drug administration and the treatment will be discontinued if intolerable toxicity or disease progression occurs during this period.

NM-IL-12 in Cutaneous T-Cell Lymphoma (CTCL) Undergoing Total Skin Electron Beam Therapy (TSEBT)

A Single Arm, Open-Label Study To Evaluate The Safety, Tolerability And Preliminary Efficacy Of NM-IL-12 (rHuIL-12) In Patients With Cutaneous T Cell Lymphoma (CTCL) Undergoing Low Dose Total Skin Electron Beam Therapy (TSEBT)

General safety: Vital signs (temperature, blood pressure, pulse rate, respiratory rate) and physical examination.

Toxicity according to the NCI CTCAE (v4.03) for AEs and clinical laboratory profile; AEs will be collected in all patients who received at least one dose of NM-IL-12 and up to four weeks post last NM-IL-12 dose.

Immunogenicity of NM-IL-12 will be evaluated by the presence of anti-drug antibody (ADA)

Exploratory skin clinical responses measured by a modified severity-weighted assessment tool (mSWAT)

Progression free survival based on every 4 week follow up after the monthly dose until one of the events below occurs first:

* Progressive disease is documented
* Another treatment for CTCL is administered (topical or systemic)
* 107 weeks are completed after the patient's first dose of NM-IL-12

National Cancer Institute (NCI)

Neumedicines Inc.

APO866 is administered as 0.126 mg/m²/hr for 4 consecutive days (96 hours), every 3 weeks for a total of 3 cycles

APO866

Reinhard Dummer, MD PhD

René Goedkoop, MD

This phase II study is designed to determine the efficacy and safety of APO866 for the treatment of patients with advanced forms of cutaneous T-cell lymphoma (CTCL). APO866 has shown to induce growth inhibition in cultures of human CTCL cells as well as in animal models with subcutaneously implanted human CTCL tumors. APO866 was considered to be safe and well-tolerated in a phase I study that treated 24 patients with advanced cancer. APO866 is administered by intravenous infusion continuously for 96 hours and that is repeated every 4 weeks. Patients will receive 3 cycles of treatment and the primary efficacy endpoint will be assessed at Week 16. patients will be followed up for 12 months

CTCL is the most frequent occurring cutaneous non-Hodgkin lymphoma characterized by an indolent and protracted course of patches, plaques and tumors. It is highly symptomatic, debilitating, disfiguring and impacting on the patient's quality of life. The treatment strategy for CTCL is based on the exact diagnosis including the stage of disease and aims to preserve cellular immune function, while achieving an anti-tumor effect. Given the nature of the disease and the cumulative and additive toxicities of treatments used, the intensity and duration of long-term therapy is limited.

APO866 is novel drug that induces cell death by specifically inhibiting the biosynthesis of NAD+ from niacinamide, which is essential for the cellular metabolism, protein modification (e.g. PARP mediated DNA repair, sirtuins (histone deacetylation)) and Calcium dependent messenger synthesis. APO866 is not subject to the commonly known mechanisms of MDR. Its activity is cell cycle independent. APO866 exerted high anti-tumor activity on a broad range of different tumor cells derived from both human solid cancers and leukemias in vitro and on large number of human xenografts in nude mice and rats in vivo. Hematologic cancer cells were highly sensitive to APO866. Lymphocytes are the most sensitive normal cells to APO866 resulting to lymphocytopenia and reticulocytopenia in rats, monkeys and cancer patients. Furthermore, APO866 may have anti-angiogenic properties as shown in vivo and in patients.

APO866 has shown to induce, at low nM level, growth inhibition of human Myla CTCL cells as well as in human subcutaneous xenografts of Myla CTCL in Balb-C nude mice.

APO866 was investigated in 24 patients with advanced cancers in a phase I study aiming to determine the DLT and MTD. Treatment was well tolerated and safe. The unique DLT was thrombocytopenia. At dose levels higher than 0.036 mg/m2/hr CTC grade III lymphocytopenia, thought not be clinically relevant, preceded all other toxicities. The recommended dose for phase II studies of APO866 is 0.126 mg/m2/hr administered by civ infusion for 4 consecutive days (MTD). This dose was selected because of its safety profile, and the translational observation that Css of APO866 at MTD was similar or higher as compared to the concentrations at which efficacy was established in vitro and in vivo.

No objective tumor response was observed. However, 4 patients had stable disease for at least 3 months: prostate cancer (4 months), melanoma (5 months), sarcomatoid mesothelioma (3 months) and oropharyngeal cancer (5 months). In addition, lesion size reductions were observed in the melanoma patient (80% size reduction and stable size of other lesions) at an APO866 dose level of 0.072 mg/m2/hr, and in the mesothelioma patient (moderate size reductions of pleural lesions) at 0.108 mg/m2/hr.

Treatment with APO866 was safe and well tolerated. The anti-tumor effect of APO866, in particular on hematological cancer cells in vitro and ex vivo, and its lymphocytopenic effect in patients support the rationale to conduct an open phase II study of APO866 in patients with refractory or relapsed CTCL qualifying for systemic chemotherapy

A Study of APO866 for the Treatment of Cutaneous T-cell Lymphoma

A Multicenter Open Label Phase II Study of to Assess the Efficacy and Safety of APO866 in the Treatment of Patients With Refractory or Relapsed Cutaneous T-cell Lymphoma

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Resminostat for Maintenance Treatment of Patients With Advanced Stage Mycosis Fungoides (MF) or Sézary Syndrome (SS)	NCT02953301	Mycosis Fungoid... Sezary Syndrome Lymphoma, T-Cel...	resminostat Placebo	18 Years -	4SC AG
Resminostat for Maintenance Treatment of Patients With Advanced Stage Mycosis Fungoides (MF) or Sézary Syndrome (SS)	NCT02953301	Mycosis Fungoid... Sezary Syndrome Lymphoma, T-Cel...	resminostat Placebo	18 Years -	4SC AG
TSEB and Brentuximab for Treatment of Mycosis Fungoides & Sezary Syndrome	NCT02822586	Mycosis Fungoid... Sézary Syndrome	TSEB Therapy Brentuximab ved...	18 Years -	Virginia Commonwealth University
Study of Oral LBH589 in Adult Participants With Refractory/Resistant Cutaneous T-Cell Lymphoma (CTCL)	NCT00490776	Cutaneous T-Cel...	Panobinostat	18 Years -	Novartis
Resminostat for Maintenance Treatment of Patients With Advanced Stage Mycosis Fungoides (MF) or Sézary Syndrome (SS)	NCT02953301	Mycosis Fungoid... Sezary Syndrome Lymphoma, T-Cel...	resminostat Placebo	18 Years -	4SC AG
Naloxone Hydrochloride Study for Relief of Pruritus in Patients With MF or SS Forms of CTCL	NCT02811783	Mycosis Fungoid... Lymphoma, T-Cel... Sézary Syndrome	Naloxone Hydroc... Placebo Lotion	21 Years -	Elorac, Inc.
Trial of Curcumin in Cutaneous T-cell Lymphoma Patients	NCT00969085	Cutaneous T-cel...	Curcumin (Turme... Questionnaires Photos	-	M.D. Anderson Cancer Center
NM-IL-12 in Cutaneous T-Cell Lymphoma (CTCL) Undergoing Total Skin Electron Beam Therapy (TSEBT)	NCT02542124	Cutaneous T Cel... Mycosis Fungoid... Sézary Syndrome	NM-IL-12 and TS...	18 Years -	Neumedicines Inc.
A Study of APO866 for the Treatment of Cutaneous T-cell Lymphoma	NCT00431912	Cutaneous T-cel...	APO866	18 Years -	Valerio Therapeutics
TSEB and Brentuximab for Treatment of Mycosis Fungoides & Sezary Syndrome	NCT02822586	Mycosis Fungoid... Sézary Syndrome	TSEB Therapy Brentuximab ved...	18 Years -	Virginia Commonwealth University
Study of Pralatrexate in Patients With Relapsed or Refractory Cutaneous T-cell Lymphoma	NCT00554827	Cutaneous T-cel...	Vitamin B12 Folic Acid Pralatrexate	18 Years -	Acrotech Biopharma Inc.

Spots Global Cancer Trial Database for sézary syndrome