Back to resultsPh II of Non-myeloablative Allogeneic Transplantation Using TLI & ATG In Patients w/ Cutaneous T Cell Lymphoma
Primary Purpose
Mycoses, Sezary Syndrome, Lymphoma, T-Cell, Cutaneous
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
anti-thymocyte globulin
cyclosporine
Lymphoid radiation
Sponsored by
About this trial
This is an interventional treatment trial for Mycoses
Eligibility Criteria
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
Sites / Locations
- Stanford University School of Medicine
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Total lymphoid irradiation & anti-thymocyte immunoglobulin
Arm Description
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.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Number of Participants With Acute Graft-versus-host Disease (GVHD)
Cumulative incidence at 6 months. GvHD was assessed using the 2015 NIH consensus criteria.
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.
Overall Survival (OS)
Overall survival (OS) is the time measurement between the day of allogeneic transplant and death from any cause (Kaplan-Meier estimate).
Overall Survival (OS)
Overall survival (OS) is the time measurement between the day of allogeneic transplant and death from any cause (Kaplan-Meier estimate).
Mortality
Total count of non-relapsed mortality and mortality from relapsed disease.
Treatment Related Mortality
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).
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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00896493
Brief Title
Ph II of Non-myeloablative Allogeneic Transplantation Using TLI & ATG In Patients w/ Cutaneous T Cell Lymphoma
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
May 2009 (undefined)
Primary Completion Date
November 6, 2021 (Actual)
Study Completion Date
December 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mycoses, Sezary Syndrome, Lymphoma, T-Cell, Cutaneous, Bone Marrow Transplant Failure, Lymphoma, Non-Hodgkin, Cutaneous T-cell Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
38 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Total lymphoid irradiation & anti-thymocyte immunoglobulin
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
anti-thymocyte globulin
Other Intervention Name(s)
ATG
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
cyclosporine
Other Intervention Name(s)
cyclosporin, cyclosporin A
Intervention Description
5 mg/kg PO or IV
Intervention Type
Radiation
Intervention Name(s)
Lymphoid radiation
Other Intervention Name(s)
Total lymphoid irradiation (TLI)
Intervention Description
TLI is administered ten times in 80c- 120c Gy fractions on day -11 through day -7 and day -4 through day -1
Primary Outcome Measure Information:
Title
Progression-Free Survival (PFS) at 180 Days
Description
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
Time Frame
180 days
Secondary Outcome Measure Information:
Title
Number of Participants With Acute Graft-versus-host Disease (GVHD)
Description
Cumulative incidence at 6 months. GvHD was assessed using the 2015 NIH consensus criteria.
Time Frame
6 months
Title
Number of Participants With Chronic Graft-versus-host Disease (GVHD)
Description
Cumulative incidence at 6 months (any grade). GvHD was assessed using the 2015 NIH consensus criteria.
Time Frame
2 years
Title
Overall Survival (OS)
Description
Overall survival (OS) is the time measurement between the day of allogeneic transplant and death from any cause (Kaplan-Meier estimate).
Time Frame
2 years
Title
Overall Survival (OS)
Description
Overall survival (OS) is the time measurement between the day of allogeneic transplant and death from any cause (Kaplan-Meier estimate).
Time Frame
5 years
Title
Mortality
Description
Total count of non-relapsed mortality and mortality from relapsed disease.
Time Frame
Up to 5 years
Title
Treatment Related Mortality
Time Frame
Up to 5 years
Title
Event Free Survival (EFS)
Description
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).
Time Frame
2 years
Title
Event Free Survival (EFS)
Description
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).
Time Frame
5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wen-Kai Weng
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University School of Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
25529383
Citation
Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, Palmer J, Weisdorf D, Treister NS, Cheng GS, Kerr H, Stratton P, Duarte RF, McDonald GB, Inamoto Y, Vigorito A, Arai S, Datiles MB, Jacobsohn D, Heller T, Kitko CL, Mitchell SA, Martin PJ, Shulman H, Wu RS, Cutler CS, Vogelsang GB, Lee SJ, Pavletic SZ, Flowers ME. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015 Mar;21(3):389-401.e1. doi: 10.1016/j.bbmt.2014.12.001. Epub 2014 Dec 18.
Results Reference
background
PubMed Identifier
7581076
Citation
Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995 Jun;15(6):825-8.
Results Reference
background
PubMed Identifier
32941647
Citation
Weng WK, Arai S, Rezvani A, Johnston L, Lowsky R, Miklos D, Shizuru J, Muffly L, Meyer E, Negrin RS, Wang E, Almazan T, Million L, Khodadoust M, Li S, Hoppe RT, Kim YH. Nonmyeloablative allogeneic transplantation achieves clinical and molecular remission in cutaneous T-cell lymphoma. Blood Adv. 2020 Sep 22;4(18):4474-4482. doi: 10.1182/bloodadvances.2020001627.
Results Reference
result
PubMed Identifier
24307695
Citation
Weng WK, Armstrong R, Arai S, Desmarais C, Hoppe R, Kim YH. Minimal residual disease monitoring with high-throughput sequencing of T cell receptors in cutaneous T cell lymphoma. Sci Transl Med. 2013 Dec 4;5(214):214ra171. doi: 10.1126/scitranslmed.3007420.
Results Reference
derived
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Ph II of Non-myeloablative Allogeneic Transplantation Using TLI & ATG In Patients w/ Cutaneous T Cell Lymphoma
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