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

Lymphoma, Non-Hodgkin Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00896493
• Other study ID #: IRB-16213
• Secondary ID: SU-04062009-2138
• Status: Completed
• Phase: Phase 2
• Start date: May 2009
• Est. completion date: December 2022

Study information

• Verified date: May 2023
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: December 2022
• Est. primary completion date: November 6, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• anti-thymocyte globulin
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
• cyclosporine
5 mg/kg PO or IV

Radiation:
• Lymphoid radiation
TLI is administered ten times in 80c- 120c Gy fractions on day -11 through day -7 and day -4 through day -1

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Stanford University

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View 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. — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Mortality	Total count of non-relapsed mortality and mortality from relapsed disease.	Up to 5 years
Secondary	Treatment Related Mortality		Up to 5 years
Secondary	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
Secondary	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