Clinical trial NCT00896493: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mycoses
Sezary Syndrome
Lymphoma, T-Cell, Cutaneous
Bone Marrow Transplant Failure
Lymphoma, Non-Hodgkin
Cutaneous T-cell Lymphoma
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2009-05-11
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-Free Survival (PFS) at 180 Days
timeFrame: 180 days
Secondary outcomes:
measure: Number of Participants With Acute Graft-versus-host Disease (GVHD)
timeFrame: 6 months
measure: Number of Participants With Chronic Graft-versus-host Disease (GVHD)
timeFrame: 2 years
measure: Overall Survival (OS)
timeFrame: 2 years
measure: Overall Survival (OS)
timeFrame: 5 years
measure: Mortality
timeFrame: Up to 5 years
measure: Treatment Related Mortality
timeFrame: Up to 5 years
measure: Event Free Survival (EFS)
timeFrame: 2 years
measure: Event Free Survival (EFS)
timeFrame: 5 years
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Wen-Kai Weng
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.