Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Antineoplastic Agents

Anti-Infective Agents

Vaccines

Molgramostim

Sargramostim

Imiquimod

Freund's Adjuvant

Dimethyl Sulfoxide

Immunologic Factors

Immunomodulating Agents

Adjuvants, Immunologic

Interferons

Protective Agents

Antioxidants

incomplete Freund's adjuvant

multi-epitope melanoma peptide vaccine

sargramostim

tetanus toxoid helper peptide

dimethyl sulfoxide

imiquimod

adjuvant therapy

Craig L. Slingluff, MD

RATIONALE: Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Biological therapies, such as imiquimod, may stimulate the immune system in different ways and stop tumor cells from growing. Giving vaccine therapy together with imiquimod after surgery may help the body kill any remaining tumor cells.

PURPOSE: This randomized phase I trial is studying the side effects and best way to give vaccine therapy with or without imiquimod in treating patients who have undergone surgery for stage II, stage III, or stage IV melanoma.

OBJECTIVES:

* Determine the safety of adjuvant transdermal vaccine therapy comprising multi-epitope melanoma peptides (MP), tetanus toxoid helper peptide (TET), and sargramostim (GM-CSF) in combination with Montanide ISA-51 or dimethyl sulfoxide with or without imiquimod in patients who have undergone surgical resection for stage II-IV melanoma.
* Determine, preliminarily, the immunogenicity of these regimens in these patients.
* Correlate, preliminarily, transdermal administration of these vaccines with the recruitment and maturation of epidermal Langerhans cells in these patients.
* Determine, preliminarily, the effects of timing of subsequent vaccine therapy comprising MP, TET, and GM-CSF emulsified in Montanide ISA-51, administered intradermally and subcutaneously, on the persistence of immune response in these patients.

OUTLINE: This is a randomized, open-label study. Patients are randomized to 1 of 4 treatment arms.

* Arm I: Patients receive vaccine therapy comprising multi-epitope melanoma peptides (MP), tetanus toxoid helper peptide (TET), and sargramostim (GM-CSF) emulsified in Montanide ISA-51 transdermally (TD) on days 1, 8, and 15. Patients then receive the vaccine intradermally (ID) and subcutaneously (SC) on days 29, 50, 71, 92, 113, and 134.
* Arm II: Patients receive vaccine therapy as in arm I. Patients also receive imiquimod topically on days 0, 7, and 14.
* Arm III: Patients receive vaccine therapy comprising MP, TET, GM-CSF, and dimethyl sulfoxide TD on days 1, 8, and 15. Patients then receive vaccine therapy comprising MP, TET, and GM-CSF emulsified in Montanide ISA-51 ID and SC on days 29, 50, 71, 92, 113, and 134.
* Arm IV: Patients receive vaccine therapy as in arm III and imiquimod as in arm II.

In all arms, treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 3 and 5 weeks and then at disease progression.

PROJECTED ACCRUAL: A maximum of 26 patients (approximately 6 per treatment arm) will be accrued for this study within approximately 2 years.

Vaccine Therapy With or Without Imiquimod in Treating Patients Who Have Undergone Surgery for Stage II, Stage III, or Stage IV Melanoma

Evaluation of Different Adjuvants for the Transdermal Administration of a Peptide-Based Vaccine in Participants With High-Risk Melanoma

National Cancer Institute (NCI)

Craig L Slingluff, Jr

Professor, Department of Surgery

Wounds and Injuries

Breast Neoplasms

Dermatitis

Radiodermatitis

Breast Diseases

Radiation Injuries

Acute Graft Versus Host Disease

Central Nervous System Depressants

Other Dietary Supplements

Melatonin

25 mg melatonin in 1 g cream twice daily for the duration of the radiation therapy

Placebos

Dennis B Zetner, MD

The aim of the present randomized double-blinded placebo-controlled clinical trial is to investigate if melatonin can protect against acute radiation dermatitis in patients with early breast cancer receiving radiation therapy, and whether this has an impact on the patients' quality of life.

The study will be a randomized, placebo-controlled, double-blinded clinical pivotal trial. Patients will be allocated in a ratio of 1:1 to the melatonin or placebo group. Patients will be stratified according to the type of surgery (lumpectomy or mastectomy). Randomization will be performed in blocks of randomized sizes. The study will be performed in the Department of Oncology, Rigshospitalet, Denmark.

Eligible patients with early breast cancer receive adjuvant radiation therapy over 15 to 30 daily fractions (5 fractions per week) of ionizing megavoltage photon radiation to a total of 40 - 60 Gy within 3-5 weeks according to the guidelines of the Danish Breast Cancer Cooperative Group. In this study, the patients will administer approximately 1 g of cream containing melatonin (25 mg/g) and dimethyl sulfoxide (DMSO) (150 mg/g) or a placebo cream topically twice daily on the irradiated skin area. The patients are scheduled to do this every day from the first to the last fraction of radiation therapy, including the days where they do not receive radiation therapy. The investigators have chosen placebo as the comparator due to it being safe and the most reasonable method of evaluating any effects of the intervention. On days where the patients receive radiation, the melatonin/DMSO or placebo cream will be applied no less than 2 hours prior to radiation. Throughout the study, the patients will meet with an investigator once weekly who will monitor compliance and assess outcomes.

Melatonin Cream Against Acute Radiation Dermatitis in Patients With Early Breast Cancer

MELADERM-trial: Melatonin Cream Against Acute Radiation Dermatitis in Patients With Early Breast Cancer: a Pivotal Phase 2, Double-blind, Randomized, Placebo-controlled Trial

This scale ranges from 0 to 4, being:

0: No change over baseline

1. Follicular, faint or dull erythema/epilation/dry desquamation/decreased sweating
2. Tender or bright erythema, patchy moist desquamation/moderate edema
3. Confluent, moist desquamation other than skin folds, pitting edema
4. Ulceration, hemorrhage, necrosis

Erythema has previously been evaluated by a validated method using software analysis (Image J, version 1.45S, National Institute of health, USA) of digital photos \[32\]. A "color space converter" function will be used to convert the clinical photos into grayscale in the software analysis. Erythema will be quantified by pixel color analyses where all white colored pixels represent erythema. An a\*-value will represent degree of erythema (high a\*-values represent a high degree of erythema).

The quality of life questionnaire determines patient-reported quality of life through a series of questions. All questions in the BR23-module (Breast cancer module) are answered on a scale of 1-4, meaning:

1. Not at all
2. A little
3. A lot
4. Very much The questions vary between symptoms, feelings and activities of daily living.

Only item 20-23 (specifically questions about the breast area) are defined as a primary outcome. All other outcomes in the questionnaire are considered secondary outcomes.

The quality of life questionnaire determines patient-reported quality of life through a series of questions. 28 of 30 questions in the C30-module (Core questionnaire) are answered on a scale of 1-4, meaning:

1. Not at all
2. A little
3. A lot
4. Very much The questions vary between symptoms, feelings and activities of daily living.

The remaining two questions are answered on a scale of 1 (Very bad) to 7 (Very well).

The quality of life questionnaire determines patient-reported quality of life through a series of questions. All questions in the BR23-module (Breast cancer module) are answered on a scale of 1-4, meaning:

1. Not at all
2. A little
3. A lot
4. Very much The questions vary between symptoms, feelings and activities of daily living.

Item 1-19 are defined as a secondary outcomes outcome.

Patients will be questioned once weekly about usage of steroid cream. The questions will be:

Have you used any steroid cream throughout your radiation therapy? (Yes/No) If yes, when did you begin using steroid cream? (Date) If yes, how many days have you used steroid cream? (Number of days)

Dennis Bregner Zetner

Principal Investigator

Symptoms and General Pathology

Blood and Lymph Conditions

Immune System Diseases

Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Hodgkin Disease

Primary Myelofibrosis

Lymphoma, Non-Hodgkin

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Bone Marrow Diseases

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Myeloproliferative Disorders

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Lymphocytic Leukemia

Chronic Myeloid Leukemia

Hodgkin Lymphoma

Chronic Myeloproliferative Disorders

Antirheumatic Agents

Dermatologic Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Melphalan

Cyclosporine

Cyclosporins

Lenograstim

Mycophenolic Acid

Immunosuppressive Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Antimetabolites

Enzyme Inhibitors

Clotrimazole

Miconazole

Antifungal Agents

Calcineurin Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

REDUCED INTENSITY CONDITIONING (RIC):

Flu/Cy/TBI: Patients receive cyclophosphamide IV over 2 hours on day -6 and fludarabine phosphate IV on days -6 to -2 and undergo total-body irradiation on day -1.

Flu/Mel: Patients receive fludarabine daily on days -5 to -2, a single dose of melphalan on day -2, and ATG on day -3 and day-2.

GVHD PROPHYLAXIS: Patients receive cyclosporine PO or IV over 2 hours every 12 hours on beginning on days -5 to 100 with taper beginning on day 100 and mycophenolate mofetil IV or PO BID on days -5 to 100.

TRANSPLANT: Patients undergo a co-transplantation of an intra-osseous umbilical cord blood transplantation and a mesenchymal stem cell transplantation on day 0.

All patients will receive a single IV dose of 50 mg/kg of cyclophosphamide on day -6

cyclophosphamide

Given by IV during prep at 40mg/m2 for 5 days

fludarabine phosphate

Undergo single fraction of reduced intensity conditioning (RIC) regimen of 200 cGy TBI without shielding on day -1

total-body irradiation

Initiated in patients on the day -5. Cyclosporine will be administered orally or intravenously at 2 mg/kg/dose every 12 hours for 2-hour period. Cyclosporine will continue until day +100

cyclosporine

Given at 1g intravenously or orally twice daily from day -5 to +100, or as clinically indicated.

mycophenolate mofetil

Following RIC, on day T+0, dimethylsulphoxide will be removed from the cord blood cells and given as transplant.

umbilical cord blood transplantation

The total dosage of hMSC will be 2x10\^6cells/kg (+/-20%).

mesenchymal stem cell transplantation

Leland Metheny, MD

This clinical trial studies intra-osseous donor umbilical cord blood and mesenchymal stromal cell co-transplant in treating patients with hematologic malignancies. Giving low doses of chemotherapy and total-body irradiation before a co-transplant of donor umbilical cord blood and mesenchymal stromal cells into the bone (intra-osseous) helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil at the time of transplant may stop this from happening.

PRIMARY OBJECTIVES:

I. To estimate the feasibility of combining intra-osseous umbilical cord blood (UCB) hematopoietic stem cells and human mesenchymal stromal cells (hMSC) following reduced intensity conditioning (RIC).

SECONDARY OBJECTIVES:

I. To estimate the time to engraftment of intra-osseous (IO) UCB transplant combined with hMSC following RIC.

II. To estimate the safety profile of IO UBC transplant combined with hMSC.

OUTLINE:

REDUCED INTENSITY CONDITIONING: Patients receive cyclophosphamide intravenously (IV) over 2 hours on day -6 and fludarabine phosphate IV on days -6 to -2 and undergo total body irradiation (TBI) on day -1.

GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive cyclosporine orally (PO) or IV over 2 hours every 12 hours on beginning on days -5 to 100 with taper beginning on day 100 and mycophenolate mofetil IV or PO twice daily (BID) on days -5 to 100.

TRANSPLANT: Patients undergo intra-osseous UCB and hMSC co-transplant on day 0.

After completion of study treatment, patients are followed up at days 28 and 100, and then at 6, 9, and 12 months.

Intra-Osseous Co-Transplant of UCB and hMSC

Intra-osseous Co-transplant of Cord Blood and Mesenchymal Stromal Cells: A Feasibility Study

Primary graft failure is defined by \<10% BM cellularity in bone marrow biopsies. Failure in more than 30% of patients will indicate unfeasibility of treatment

Primary graft failure is defined by \<500 ANC cell/ul in bone marrow biopsies. Failure in more than 30% of patients will indicate unfeasibility of treatment

Primary graft failure is defined by hematopoietic recovery with \<10% donor cell chimerism. Failure in more than 30% of patients will indicate unfeasibility of treatment

Primary graft failure is defined by hematopoietic recovery with \<40% donor cell chimerism. Failure in more than 30% of patients will indicate unfeasibility of treatment

The rate of neutrophil recovery and median time of recovery will be estimated using the methods of Kaplan and Meier.

The rate of platelet recovery and median time of recovery will be estimated using the methods of Kaplan and Meier.

The median time of neutrophil recovery will be estimated using the methods of Kaplan and Meier.

The median time of platelet recovery will be estimated using the methods of Kaplan and Meier.

Case Comprehensive Cancer Center

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Vaccine Therapy With or Without Imiquimod in Treating Patients Who Have Undergone Surgery for Stage II, Stage III, or Stage IV Melanoma	NCT00118313	Melanoma (Skin)	incomplete Freu... multi-epitope m... sargramostim tetanus toxoid ... dimethyl sulfox... imiquimod adjuvant therap...	12 Years - 120 Years	University of Virginia
Vaccine Therapy With or Without Imiquimod in Treating Patients Who Have Undergone Surgery for Stage II, Stage III, or Stage IV Melanoma	NCT00118313	Melanoma (Skin)	incomplete Freu... multi-epitope m... sargramostim tetanus toxoid ... dimethyl sulfox... imiquimod adjuvant therap...	12 Years - 120 Years	University of Virginia
Melatonin Cream Against Acute Radiation Dermatitis in Patients With Early Breast Cancer	NCT03716583	Radiation Derma... Radiation Derma... Breast Cancer	Melatonin Dimethyl Sulfox... Placebos	50 Years -	Herlev Hospital
Melatonin Cream Against Acute Radiation Dermatitis in Patients With Early Breast Cancer	NCT03716583	Radiation Derma... Radiation Derma... Breast Cancer	Melatonin Dimethyl Sulfox... Placebos	50 Years -	Herlev Hospital
Intra-Osseous Co-Transplant of UCB and hMSC	NCT02181478	Acute Lymphobla... Acute Myelogeno... Myelodysplastic... Myelofibrosis Relapsed Non-Ho... Refractory Non-... Hodgkin Lymphom... Refractory Hodg... Relapsed Chroni... Refractory Chro... Lymphoid Malign... Chronic Myeloge...	cyclophosphamid... fludarabine pho... total-body irra... cyclosporine mycophenolate m... umbilical cord ... mesenchymal ste...	18 Years - 75 Years	Case Comprehensive Cancer Center

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