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

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

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).

Study Overview

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

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 Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Total lymphoid irradiation & anti-thymocyte immunoglobulin; 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; 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; Other Names: ATG; Drug: cyclosporine; 5 mg/kg PO or IV; Other Names: cyclosporin; cyclosporin A; 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; Other Names: Total lymphoid irradiation (TLI)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Wen-Kai Weng, Stanford University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): November 6, 2021
• Study Completion (Actual): December 1, 2022

Study Registration Dates

• First Submitted: May 7, 2009
• First Submitted That Met QC Criteria: May 8, 2009
• First Posted (Estimate): May 11, 2009

Study Record Updates

• Last Update Posted (Actual): May 11, 2023
• Last Update Submitted That Met QC Criteria: May 9, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Bacterial Infections and Mycoses; Lymphoma; Lymphoma, Non-Hodgkin; Mycoses; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous; Sezary Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Antilymphocyte Serum; Cyclosporine; Cyclosporins
• Other Study ID Numbers: IRB-16213; SU-04062009-2138 (Other Identifier: Stanford University); 16213 (Other Identifier: Stanford IRB); BMT206 (Other Identifier: OnCore)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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