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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00896493

Enrollment

Registered

2009-05-11

Start date

2009-05-31

Completion date

2022-12-31

Last updated

2023-05-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

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.

Interventions

DRUGanti-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

DRUGcyclosporine

5 mg/kg PO or IV

RADIATIONLymphoid radiation

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

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Progression-Free Survival (PFS) at 180 Days	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

Measure	Time frame	Description
Number of Participants With Chronic Graft-versus-host Disease (GVHD)	2 years	Cumulative incidence at 6 months (any grade). GvHD was assessed using the 2015 NIH consensus criteria.
Overall Survival (OS)	2 years	Overall survival (OS) is the time measurement between the day of allogeneic transplant and death from any cause (Kaplan-Meier estimate).
Number of Participants With Acute Graft-versus-host Disease (GVHD)	6 months	Cumulative incidence at 6 months. GvHD was assessed using the 2015 NIH consensus criteria.
Treatment Related Mortality	Up to 5 years	—
Event Free Survival (EFS)	2 years	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).
Mortality	Up to 5 years	Total count of non-relapsed mortality and mortality from relapsed disease.

Countries

United States

Participant flow

Participants by arm

Arm	Count
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.	38
Total	38

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Early disease relapse	3

Baseline characteristics

Characteristic	Total Lymphoid Irradiation & Anti-thymocyte Immunoglobulin
Active disease at the time of conditioning Blood	12 Participants
Active disease at the time of conditioning Lymph node	22 Participants
Active disease at the time of conditioning Skin	35 Participants
Active disease at the time of conditioning Visceral (site: bone marrow)	4 Participants
Active disease at the time of conditioning Visceral (site: tonsil)	1 Participants
Age, Continuous	62 years
Diagnosis Mycosis fungoides	20 Participants
Diagnosis Sezary Syndrome	18 Participants
Donor Sibling	13 Participants
Donor Unrelated - matched	15 Participants
Donor Unrelated - unmatched	7 Participants
Donor-recipient cytomegalovirus (CMV) status Donor and/or recipient seropositive	27 Participants
Donor-recipient cytomegalovirus (CMV) status Donor and recipient seronegative	8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	35 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race/Ethnicity, Customized Asian	2 Participants
Race/Ethnicity, Customized Black	4 Participants
Race/Ethnicity, Customized Caucasian	31 Participants
Race/Ethnicity, Customized Unknown/not reported	1 Participants
Region of Enrollment United States	38 Participants
Retro-CLIPI High risk	18 Participants
Retro-CLIPI Intermediate risk	13 Participants
Retro-CLIPI Low risk	4 Participants
Sex: Female, Male Female	16 Participants
Sex: Female, Male Male	22 Participants
Time from diagnosis to allogeneic HCT	40 months

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	21 / 38
other Total, other adverse events	20 / 38
serious Total, serious adverse events	7 / 38

Outcome results

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

Time frame: 180 days