Ph II of Non-myeloablative Allogeneic Transplantation Using TLI & ATG In Patients w/ Cutaneous T Cell Lymphoma

Study Overview
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Brief Summary
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Non-myeloablative approach for allogeneic transplant is a reasonable option, especially given that the median age at diagnosis is 55-60 years and frequently present compromised skin in these patients, which increases the risk of infection. Therefore, we propose a clinical study with allogeneic hematopoietic stem cell transplantation (HSCT) using a unique non-myeloablative preparative regimen, TLI/ATG, to treat advanced mycosis fungoides/Sezary syndrome (MF/SS).

Detailed Description
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Primary Objectives -To evaluate the graft versus lymphoma effect by monitoring rate of clinical response, event-free and overall survival. Secondary Objectives -To evaluate the incidence and extent of acute and chronic graft-versus-host disease (GVHD) and time to engraftment.

Official Title
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A Phase II Study of Non-myeloablative Allogeneic Transplantation Using Total Lymphoid Irradiation (TLI) and Antithymocyte Globulin (ATG) In Patients With Cutaneous T Cell Lymphoma

Conditions
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Mycoses, Sezary Syndrome, Lymphoma, T-Cell, Cutaneous, Bone Marrow Transplant Failure, Lymphoma, Non-Hodgkin, Cutaneous T-cell Lymphoma

Intervention / Treatment
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* Drug: anti-thymocyte globulin
* Drug: cyclosporine
* Radiation: Lymphoid radiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage IIB-IV mycosis fungoides or Sezary syndrome, who have failed at least 1 standard systemic therapy or are not candidates for standard therapy. Pathology reviewed and the diagnosis confirmed at Stanford University Medical Center. Age > 18 years and <= 75 years. Karnofsky Performance Status >= 70%. Corrected DLCO >= 40% Left ventricle ejection fraction (LVEF) > 30%. ALT and AST must be <= 3X normal. Total bilirubin <= 3 mg/dL unless hemolysis or Gilbert's disease. Estimated creatinine clearance >= 50 ml/min. Have a related or unrelated HLA-identical donor or one antigen/allele mismatched in HLA-A, B, C or DRB1. Signed informed consent. Patients with prior malignancies diagnosed > 5 years ago without evidence of disease are eligible. Patients with a prior malignancy treated < 5 years ago but have a life expectancy of > 5 years for that malignancy are eligible. Donor Inclusion Criteria Age >=17. HIV seronegative. No contraindication to the administration of G-CSF. Willing to have a central venous catheter placed for apheresis if peripheral veins are inadequate Exclusion Criteria: Uncontrolled active infection. Uncontrolled congestive heart failure or angina. Pregnancy or nursing patients will be excluded from the study. Those who are HIV-positive will be excluded from the study due to high risk of lethal infection after hematopoietic cell transplantation. Donor Exclusion Criteria Serious medical or psychological illness. Pregnant or lactating women are not eligible Prior malignancies within the last 5 years except for non-melanoma skin cancers

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Total lymphoid irradiation & anti-thymocyte immunoglobulin<br>TLI is administered from a 6 MeV linear accelerator in 80c- 120c Gy fractions. Anti-thymocyte-Globulin (ATG) is administered intravenously for a total dose of 7.5 mg/kg. | Drug: anti-thymocyte globulin<br>* ATG will be administered five times intravenously at 1.5 mg/kg/day from day -11 through day -7 for a total dose of 7.5 mg/kg<br>* Other names: ATG;Drug: cyclosporine<br>* 5 mg/kg PO or IV<br>* Other names: cyclosporin A;Radiation: Lymphoid radiation<br>* TLI is administered ten times in 80c- 120c Gy fractions on day -11 through day -7 and day -4 through day -1<br>* Other names: Total lymphoid irradiation (TLI);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) at 180 Days | Progression-Free Survival (PFS; time to disease progression or death from any cause) assessed at 180 days (Kaplan-Meier estimate). Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions | 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Acute Graft-versus-host Disease (GVHD) | Cumulative incidence at 6 months. GvHD was assessed using the 2015 NIH consensus criteria. | 6 months | 
| Number of Participants With Chronic Graft-versus-host Disease (GVHD) | Cumulative incidence at 6 months (any grade). GvHD was assessed using the 2015 NIH consensus criteria. | 2 years | 
| Overall Survival (OS) | Overall survival (OS) is the time measurement between the day of allogeneic transplant and death from any cause (Kaplan-Meier estimate). | 2 years | 
| Overall Survival (OS) | Overall survival (OS) is the time measurement between the day of allogeneic transplant and death from any cause (Kaplan-Meier estimate). | 5 years | 
| Mortality | Total count of non-relapsed mortality and mortality from relapsed disease. | Up to 5 years | 
| Treatment Related Mortality |  | Up to 5 years | 
| Event Free Survival (EFS) | Event-free survival (EFS) is the time measurement between the day of allogeneic transplant and the first documented recurrence or death from any cause (Kaplan-Meier estimate). | 2 years | 
| Event Free Survival (EFS) | Event-free survival (EFS) is the time measurement between the day of allogeneic transplant and the first documented recurrence or death from any cause (Kaplan-Meier estimate). | 5 years |