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Cyclosporin beginning day -4 then stem cells given on Day 0 followed by intravenous Methotrexate on days +1, +3, and +6.

Cyclosporin beginning day -4 and intravenous Methotrexate on days +1, +3, and +6 will be given

methotrexate

Cyclosporin

Richard W Childs, M.D.

The goal of this research study is to identify other types of cancer (malignant neoplasms) that may be treatable with stem cell transplantation (allogenic peripheral blood stem cell transplantation.

Patients with a variety of different types of cancerous tumors that have spread (metastasized) and whose conditions have not improved with stand therapy, will be eligible to participate. Those patients selected to participate in the study will undergo a procedure known as a "mini-transplant". The mini-transplant is a transplantation of stem-cells collected from a sibling (brother or sister) of the patient. Unlike traditional bone marrow transplants, the mini-transplant does not require intense chemotherapy or radiation therapy. Because of this, patients experience fewer and less severe side effects.

This study is open to patients diagnosed with a variety of metastatic solid tumors including esophageal, gastric (stomach), colon, rectal, liver tumors (hepatoma), cancer of the biliary system (cholangiocarcinoma), cancer of the pancreas, lung, breast, prostate, bone (sarcoma), adrenal basal cell, bladder, and adenocarcinomas of unk primary origin.

The main objective of this study is to identify metastatic neoplasms, which may be susceptible to the GVT effect. We will treat patients with progressive metastatic solid tumors refractory to standard therapy with a non-myeloablative allogeneic PBSC transplant from a family donor. A GVT effect from immunocompetent donor immune cells could extend life expectancy and possibly cure such patients.

Eligible patients will be treated with an allogeneic peripheral blood stem cell transplant from an HLA identical or single HLA antigen-mismatched family donor, using an intensive immunosuppressive regimen without myeloablation ("mini-transplant") in an attempt to decrease the transplant related toxicities while preserving the anti-malignancy and/or anti-host marrow effect of the graft. The low intensity non-myeloablative conditioning regimen should provide adequate immunosuppression to allow stem cell and lymphocyte engraftment. A T-cell replete, donor-derived, granulocyte colony stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSC) will be used to establish hematopoietic and lymphoid reconstitution. We will infuse lymphocytes in patients with \<100% donor T-cell chimerism or with evidence of tumor progression in an attempt to prevent graft rejection and enhance a graft-versus-malignancy effect, respectively.

This trial is open to several different types of metastatic, treatment-refractory, solid neoplasms, breast, cholangiocarcinoma, small intestine/colon/rectal adenocarcinoma, esophageal/gastric, hepatocellular, pancreatic, prostate, and bony/soft tissue sarcomas. The trial design permits up to 10 patients with a specific tumor type to be enrolled to screen for anti-tumor effects. A single complete response in a specific tumor type is an indication to exclude further patients with that diagnosis from the study. Subsequently, a new protocol which focuses on further defining a GVT effect in that disease category will be instituted.

Stem Cell Transplantation for Metastatic Solid Tumors

Exploratory Study of Non-Myeloablative Allogeneic Stem Cell Transplantation and Donor Lymphocyte Infusions for Metastatic Neoplasms Refractory to Standard Therapy

To identify an anti-tumor effect of allogenic PNSC transplantation by induction of a graft-versus-tumor (GVT) effect in patients with a diversity of metastatic solid tumors, which are refractory to standard therapy.

Tumor response assessed as follows:

Complete response (CR): disappearance of all signs and symptoms of metastatic disease for a period of at least one month.

Partial response (PR): a 50% or greater decrease in the sum of the products of the longest perpendicular diameters of all measured lesions lasting for a period of at least one month. No new metastatic lesions may appear.

Stable disease (SD): tumor measurements not meeting the criteria of CR, PR, or PD.

Progressive disease (PD): increase of 25% or greater in the sum of the products of the longest perpendicular diameters of all measured lesions compared to the smallest previous measurements, or the development of any new metastatic disease.

Number of participants that achieved engraftment based on blood Chimerism Cluster of differentiation 3 (CD3) analysis that is greater than or equal to 95%.

To evaluate the effects of donor lymphocyte infusion (DLI) and cyclosporine A (CSA) withdrawal on tumor regression in participants who show progressive disease off of CSA and in the absence of grade \> II GVHD, or who are at risk for graft failure due to incomplete donor T-cell engraftment will receive one or more DLI.

Tumor response assessed as follows:

Complete response (CR): disappearance of signs \& symptoms of metastatic disease at least one month.

Partial response (PR): a 50% or greater decrease in the sum of the products of the longest perpendicular diameters of all measured lesions lasting at least one month. No new metastatic lesions may appear.

Stable disease (SD): tumor measurements not meeting the criteria of CR, PR, or PD.

Progressive disease (PD): increase of 25% or greater in the sum of the products of the longest perpendicular diameters of all measured lesions compared to the smallest previous measurements, or development of new metastatic disease.

Number of participants who developed Acute Graft vs Host Disease (GVHD) Grades I, II, III, IV as defined by CIMBTR criteria for Organ Stages of Acute GVHD.

Grades are defined as:

Grade I: Skin = Maculopapular rash\< 25% of body surface area (BSA); Liver = Total Bilirubin 2-3 mg/dL; Lower GI = stool output/day is 500-999 mL/day.

Grade II: Skin = rash on 25-50 percent body surface area; Liver = Total Bilirubin 3.1-6.0 mg/dL; Lower GI = Diarrhea 1001-1500 mL/day.

Grade III: Skin = Rash on \>50% of body surface; Liver = Total Bilirubin 6.1 - 15.0 mg/dL; Lower GI = Diarrhea \> 1500 mL/day.

Grade IV: Skin = Generalized erythroderma plus bullous formation; Liver = Total Bilirubin \>15 mg/dL; Lower GI = Severe abdominal pain with or without ileus.

Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.

Number of participants who developed Chronic Graft vs Host Disease (GVHD).

Chronic GVHD is defined as symptoms that persist or appear after 100 days since the time of stem cell transplantation.

National Heart, Lung, and Blood Institute (NHLBI)

CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given

methotrexate: CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given

cyclosporin: CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given

Stem Cell Transplantation in Patients With Progressive and Incurable Metastatic Solid Tumors

Male

Female

22 male participants and 20 female participants for total of 42 participants

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Richard Childs, M.D. Principal Investigator, NIH, NHLBI

Number of Participants Based on Tumor Response Criteria With Anti-tumor Effect Induce by Graft-versus-tumor Effect.

Number of Participants That Achieved Engraftment

Number of Participants Who Received Donor Lymphocyte Infusion to Achieve Tumor Regression or Prevent Graft Failure

Number of Participants Who Developed Acute GVHD Grade 2 and Higher

1 participant passed away prior to day 100 therefore is not evaluable.

Number of Participants Who Developed Chronic GVHD

Overall Study

Blood and Lymph Conditions

Leukemia

Leukemia, Lymphoid

Leukemia, Large Granular Lymphocytic

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

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Immunoproliferative Disorders

Leukemia, T-Cell

Aggressive NK Cell Leukemia

T-cell Large Granular Lymphocyte Leukemia

Central Nervous System Depressants

Other Dietary Supplements

Liver Extracts

Benzocaine

Tannic Acid

Large Granular Lymphocyte Leukemia (LGL) is a low grade non-Hodgkins lymphoma characterized by tissue invasion of the marrow, spleen, and liver. Cyclosporine 5-10 mg/kg/day was administered as an oral preparation given every 12 hours. Doses are adjusted to maintain a therapeutic level between 200-400 ng/ml.

An oral preparation given every 12 hours, 5-10 mg/kg/day in divided doses. Doses are adjusted to maintain a therapeutic level between 200-400 ng/ml. Levels will be checked twice weekly and once the patient has achieved steady state levels they shall be monitored once every 2 weeks. These therapeutic levels shall be maintained for 3 months.

A permutation test will be performed to examine whether the overall expression profile changes due to treatment. This will be done by comparing the number of significant genes to the distribution of this number if in fact there is no difference between pre-treatment and post-treatment gene expression.

Gene expression analysis

Gene expression profiling will be carried out on Affymetrix microarrays to compare pretreatment and posttreatment samples.

Microarray analysis

Analysis of differential gene expression profiles in patients with LGL leukemia treated with cyclosporine.

Laboratory biomarker analysis

Thomas Waldmann, M.D.

Background:

* Large granular lymphocyte (LGL) leukemia is a low-grade non-Hodgkin's lymphoma.
* LGL is associated with low numbers of white blood cells (leading to recurring infections), red blood cells (causing anemia) and platelets (causing abnormal bleeding).
* Cyclosporine (CSA) is an immunosuppressive drug that improves low blood cell counts in about 50 percent of patients with LGL leukemia.

Objectives:

* To identify what factors determine why cyclosporine works in some patients and not in others.
* To identify what causes low blood counts in LGL leukemia.

Eligibility: Patients 18 years of age and older with LGL leukemia.

Design:

* Patients have a medical history, physical examination blood tests, bone marrow biopsy and x-ray studies, including chest x-rays and computed tomography (CT) scans of the chest, abdomen and pelvis. Patients with an easily accessible enlarged lymph node have a node biopsy (removal of a small piece of tissue for microscopic examination).
* Patients take cyclosporine twice a day by mouth. Blood samples are taken at least weekly to adjust the cyclosporine dosing to maintain therapeutic serum levels.
* Patients undergo apheresis (collection of white blood cells) at a number of different time points in the study (maximum 6 times) to look at the differences in the leukemia cells before and during treatment with cyclosporine. For apheresis, blood is withdrawn through a needle in an arm vein and directed through a catheter (plastic tube) into a machine that separates it into its components. The white cells are extracted and the rest of the blood is returned through the same needle or through a second needle in the other arm.

Background:

* LGL leukemia is a low grade non-Hodgkins Lymphoma characterized by tissue invasion of the marrow, spleen and liver
* Recurrent infections due to chronic neutropenia and transfusion-dependent anemia are the principal causes for initiation of therapy
* Approximately 50% of patients treated with cyclosporine (CSA) respond to treatment. CSA appears to correct the associated cytopenia without decreasing LGL numbers, suggesting it may inhibit LGL secretion of yet unidentified mediators of neutropenia and anemia.
* Analysis of differential gene expression profiles in patients with LGL leukemia treated with cyclosporine has the potential to detect as yet unidentified, therapeutic targets and possibly provide predictors of CSA responsiveness.

Objective:

* Identify changes in gene expression patterns induced by cyclosporine therapy in patients with LGL leukemia
* Identify differences between responding and non-responding patients

Eligibility:

-Patients with Large Granular Lymphocyte leukemia

Design:

* Patients will be treated with cyclosporine at a dose of 5-10mg/kg/day in divided doses, with doses adjusted to maintain a therapeutic serum level between 200-400ng/ml. These therapeutic levels shall be maintained for 3 months.
* Tumor response will be evaluated after 3 months therapy, the dose of CsA may then be tapered to that required to sustain a response or discontinued if no evidence of response, or after relapse.
* Blood sampling or Lymphapheresis for collection of circulating malignant cells will be performed at a number of different time points. Gene expression profiling will be carried out on Affymetrix microarrays to compare pretreatment and post-treatment samples.

Effect of Cyclosporine Therapy on Gene Expression in Patients With Large Granular Lymphocyte Leukemia

Microarray Analysis of the Effect of Cyclosporine Therapy on Gene Expression Patterns in Large Granular Lymphocytic Leukemia

The goal was to examine which genes had a 2-fold gene expression between pre-treatment (baseline) and post treatment (12 weeks). Genes significant at the 0.001 level will be considered as differentially expressed due to treatment.

Here are the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.

National Cancer Institute (NCI)

Principal Investigator

LGL Patients Administered Cyclosporine

Age, Categorical

As there were only 5 patients treated, the primary endpoints of this protocol were not met and there is not enough data generated for statistical analysis. This protocol is being terminated due to low accrual and the investigator leaving the NIH.

This outcome measure was not performed because there were insufficient data points to provide any statistical power.

Changes in Gene Expression Patterns

Number of Participants With Adverse Events

Anti-Inflammatory Agents

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Everolimus

Prednisolone

Mycophenolic Acid

Methylprednisolone

Basiliximab

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Glycyrrhetinic Acid

Sirolimus

Temsirolimus

MTOR Inhibitors

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Glucocorticoids

Hormones

Hormone Antagonists

Protective Agents

Antineoplastic Agents, Hormonal

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

Simulect + cyclosporine + Myfortic + steroid stop at 3 months

Simulect + cyclosporine (decrease dose in one week at month 3 and replace by Everolimus (Certican)) + Myfortic + steroid maintenance

Cyclosporine (Group 1):

basiliximab dose: 1x20 mg IV on Day 0 and 1x20 mg IV on Day 4

Cyclosporine: 8 mg/kg PO given before surgery, followed by 2x4 mg/kg/d. C-0h levels: month 1: 150-250 ng/ml; month 2: 100-200 ng/ml; month 3: withdrawal steroids: 100-150 ng/ml.

C-2h levels: month 1: 900-1100 ng/ml; month 2: 800-1000 ng/ml; month 3: withdrawal steroids: maintain level of 750 ng/ml

Enteric-coated mycophenolate(MPA):720mg PO pre-operatively followed by 1.44 g/day.

Steroids: pre-operatively: 250mg methylprednisolone IV; day 1:125mg IV.

Methylprednisolone:day 2-30:PO 12mg/d; day 31-60:tapered to 8mg/d ,day 61-90 :4mg/d; Month 3:stop

cyclosporine

Everolimus (Group 2):

Basiliximab dose: idem as in group 1

Cyclosporine: first three months idem group 1; month 3: decreased dose by 50%, simultaneously initiate everolimus at a starting dose of 0.75 mg bid.

Once the everolimus blood levels range 6 - 12 ng/ml, cyclosporine will be stopped.

Enteric-coated mycophenolate (MPA) dosing idem as group 1.

Everolimus starting dose: 0.75 mg bid, trough levels: 6-12 ng/ml.

Steroid dosing: idem group 1, but maintained at 4 mg methylprednisolone after day 60.

Jean-Louis Bosmans, MD/PhD

Daniel Abramowicz, MD/PhD

Jacques Sennesael, MD/PhD

Jacques Sennesael, MD

Angelika Jurgens, Study Coord.

Patrick Peeters, MD/PhD

Patrick Peeters, MD

Catherine Bonvoisin, MD/PhD

Catherine Bonvoisin, MD

This study intends to determine whether steroid withdrawal or calcineurin inhibitor withdrawal is superior for graft function and graft survival. Secondary endpoints for this study are: incidence of tumors and cardiovascular events.

The primary objective: To assess if superior graft function (glomerular filtration rate (GFR) difference of 10 ml/min) will be achieved at 1 year after transplantation in cohorts of de novo kidney transplant patients treated with Myfortic-everolimus plus steroids compared to Myfortic-cyclosporine.

Methodology:

* A 5-year, multicentre, prospective, randomized, open-label, controlled study

  * Group 1: Simulect + cyclosporine + Myfortic + steroid stop at 3 months
  * Group 2: Simulect + cyclosporine (decrease dose in one week at month 3 and replace by everolimus) + Myfortic + steroid maintenance.
* In both groups MPA AUC monitoring will be done at 5-7 days and at 3 months, to ensure sufficient MPA protection.

Sample size calculations:

A total of 152 patients will be randomized (76 patients per group)

Population:

De novo kidney transplant recipients.

Study duration:

1.5 years inclusion+ follow-up during the first 5 years

Calcineurin Inhibitor (CNI) Versus Steroid Cessation in Renal Transplantation

Impact of Cyclosporine or Steroid Withdrawal at 3 Months Post Transplantation on Graft Function, Patient Survival and Cardiovascular Surrogate Markers the First 5 Years After Renal Transplantation.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Stem Cell Transplantation for Metastatic Solid Tumors	NCT00001880	Neoplasm Metast...	methotrexate Cyclosporin	10 Years - 80 Years	National Institutes of Health Clinical Center (CC)
Effect of Cyclosporine Therapy on Gene Expression in Patients With Large Granular Lymphocyte Leukemia	NCT00363779	Large Granular ... LGL Leukemia	Cyclosporine Gene expression... Microarray anal... Laboratory biom...	18 Years -	National Institutes of Health Clinical Center (CC)
Calcineurin Inhibitor (CNI) Versus Steroid Cessation in Renal Transplantation	NCT00903188	Renal Transplan...	cyclosporine Everolimus	18 Years -	University Hospital, Antwerp
Stem Cell Transplantation for Metastatic Solid Tumors	NCT00001880	Neoplasm Metast...	methotrexate Cyclosporin	10 Years - 80 Years	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for cyclosporin

Every month we try and update this database with for cyclosporin cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for cyclosporin

Every month we try and update this database with for cyclosporin cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for cyclosporin cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.