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

NCT00896493 | Completed Phase 2 Results DMC FDA Drug

• 4 other identifiers: IRB-16213SU-04062009-213816213BMT206
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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).

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Number of Participants With Acute Graft-versus-host Disease (GVHD)

  6 months

• Number of Participants With Chronic Graft-versus-host Disease (GVHD)

  2 years

• Overall Survival (OS)

  2 years

• Overall Survival (OS)

  5 years

• Mortality

  Up to 5 years

Study Arms (1)

Total lymphoid irradiation & anti-thymocyte immunoglobulin

EXPERIMENTAL

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; Drug: cyclosporine; Radiation: Lymphoid radiation

Interventions

anti-thymocyte globulin DRUG

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

Also known as: ATG

Total lymphoid irradiation & anti-thymocyte immunoglobulin

cyclosporine DRUG

5 mg/kg PO or IV

Also known as: cyclosporin, cyclosporin A

Total lymphoid irradiation & anti-thymocyte immunoglobulin

Lymphoid radiation RADIATION

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

Also known as: Total lymphoid irradiation (TLI)

Total lymphoid irradiation & anti-thymocyte immunoglobulin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age \>=17.
• HIV seronegative.
• No contraindication to the administration of G-CSF.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Related Publications (4)

• 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.

  PMID: 25529383 BACKGROUND

• 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.

  PMID: 7581076 BACKGROUND

• 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.

  PMID: 32941647 RESULT

• 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.

  PMID: 24307695 DERIVED

MeSH Terms

Conditions

Mycoses; Sezary Syndrome; Lymphoma, T-Cell, Cutaneous; Lymphoma, Non-Hodgkin

Interventions

Antilymphocyte Serum; Cyclosporine; Lymphatic Irradiation

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections; Lymphoma, T-Cell; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Radiotherapy; Therapeutics

Results Point of Contact

• Title: Wen-Kai Weng, Associate Professor of Medicine
• Organization: Stanford University Medical Center

wkweng@stanford.edu

650-723-7689

Study Officials

• Wen-Kai Weng

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: May 7, 2009
• First Posted: May 11, 2009
• Study Start: May 1, 2009
• Primary Completion: November 6, 2021
• Study Completion: December 1, 2022
• Last Updated: May 11, 2023
• Results First Posted: May 11, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)