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

Phase 2

Completed

• Conditions: Lymphoma, T-Cell, Cutaneous; Cutaneous T-cell Lymphoma; Mycoses; Sezary Syndrome; Bone Marrow Transplant Failure; Lymphoma, Non-Hodgkin
• Interventions: Drug: anti-thymocyte globulin; Drug: cyclosporine; Radiation: Lymphoid radiation

• Registration Number: NCT00896493
• Lead Sponsor: Stanford University

Brief Summary

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

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.

Study Timeline

• Study Start: 2009-05
• Study First Submitted: 2009-05-07
• Study First Submitted QC: 2009-05-08
• Study First Posted: 2009-05-11
• Primary Completion: 2021-11-06
• Study Completion: 2022-12
• Results First Submitted: 2023-03-28
• Status Verified: 2023-05
• Results First Submitted QC: 2023-05-09
• Last Update Submitted: 2023-05-09
• Results First Posted: 2023-05-11
• Last Update Posted: 2023-05-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 38

Inclusion Criteria

1. Stage IIB-IV mycosis fungoides or Sezary syndrome, who have failed at least 1 standard systemic therapy or are not candidates for standard therapy.
2. Pathology reviewed and the diagnosis confirmed at Stanford University Medical Center.
3. Age > 18 years and <= 75 years.
4. Karnofsky Performance Status >= 70%.
5. Corrected DLCO >= 40%
6. Left ventricle ejection fraction (LVEF) > 30%.
7. ALT and AST must be <= 3X normal. Total bilirubin <= 3 mg/dL unless hemolysis or Gilbert's disease.
8. Estimated creatinine clearance >= 50 ml/min.
9. Have a related or unrelated HLA-identical donor or one antigen/allele mismatched in HLA-A, B, C or DRB1.
10. Signed informed consent.
11. Patients with prior malignancies diagnosed > 5 years ago without evidence of disease are eligible.
12. 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

1. Age >=17.
2. HIV seronegative.
3. No contraindication to the administration of G-CSF.
4. Willing to have a central venous catheter placed for apheresis if peripheral veins are inadequate

Exclusion Criteria

1. Uncontrolled active infection.
2. Uncontrolled congestive heart failure or angina.
3. Pregnancy or nursing patients will be excluded from the study.
4. 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

1. Serious medical or psychological illness.
2. Pregnant or lactating women are not eligible
3. Prior malignancies within the last 5 years except for non-melanoma skin cancers

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Total lymphoid irradiation & anti-thymocyte immunoglobulin	cyclosporine	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.
Total lymphoid irradiation & anti-thymocyte immunoglobulin	Lymphoid radiation	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.
Total lymphoid irradiation & anti-thymocyte immunoglobulin	anti-thymocyte globulin	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.

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS) at 180 Days	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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Stanford University School of Medicine; 🇺🇸 Stanford, California, United States