Total Body Irradiation +/- Total Lymphoid Irradiation & Anti-Thymocyte Globulin in Non-myeloablative Hematopoietic Cell Transplantation

Acute Myeloid Leukemia Clinical Trial

Official title:

Very Low-dose Total Body Irradiation in Combination With Total Lymphoid Irradiation and Anti-Thymocyte Globulin to Improve Donor Engraftment in Patients Undergoing Non-Myeloablative Hematopoietic Cell Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03734601
• Other study ID #: IRB-47407
• Secondary ID: BMT330IRB-47407
• Status: Completed
• Phase: Phase 2
• Start date: November 5, 2018
• Est. completion date: November 17, 2020

Study information

• Verified date: May 2021
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate whether addition of a low dose of total body irradiation (TBI) to a standard preparation for transplant [total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG)] conditioning will help to augment donor chimerism without reducing tolerability of this regimen or increasing the risk of graft-vs-host disease (GVHD)

Description:

Primary Objective:

• Determine the proportion of patients with full donor T-cell chimerism at Day 28 following hematopoietic cell transplantation.

Secondary Objectives:

• Determine the risk of disease progression, overall and event free survival, and non-relapse mortality, following treatment with TLI; ATG; and TBI.

• Determine the incidence of acute and chronic GVHD following treatment with TLI; ATG; and TBI.

Exploratory Objectives:

• Determine the changes in frequency of hematopoietic stem, progenitor, and mature cell subsets and the changes in cytokine milieu and cellular architecture in the bone marrow of patients receiving TLI compared to TLI+TBI.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: November 17, 2020
• Est. primary completion date: December 26, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

INCLUSION CRITERIA

• Has a human leukocyte antigen (HLA)-matched or single allele mismatched adult sibling donor or unrelated donor.

• Acute myeloid leukemia (AML); myelodysplastic syndrome (MDS); myeloproliferative disease syndrome (MPD)]; chronic lymphocytic leukemia (CLL); B- or T-cell non Hodgkin lymphoma (NHL); Hodgkin lymphoma (HL); or chronic myelomonocytic leukemia (CMML), suitable for treatment with allogeneic transplant after TLI and ATG reduced intensity conditioning.

• Considered at high-risk for regimen-related toxicity from fully-ablative transplant conditioning (therefore reduced-intensity conditioning is recommended).

• Ability to understand and the willingness to sign a written informed consent document. Patients must have signed informed consent to participate in the trial.

EXCLUSION CRITERIA

• Uncontrolled bacterial, viral or fungal infection defined as currently taking medication and progression of clinical symptoms.

• Progressive hemato lymphoid malignancy despite conventional therapy.

• Chronic myelogenous leukemia (CML).

• Active CNS involvement of the underlying malignancy.

• HIV positive

• Pregnant or lactating

• Prior malignancy (EXCEPTION: diagnosed > 5 years ago without evidence of disease, OR treated = 5 years ago but have a greater than 50% chance of life expectancy of = 5 years for that malignancy).

• Have a psychiatric disorder(s) or psychosocial circumstance(s) which in the opinion of the primary physician would place the patient at an unacceptable risk from transplant.

• Left ventricular ejection fraction (LEVF) < 30%, or uncontrolled cardiac failure

• Diffusing capacity of lung for carbon monoxide (DLCO) < 40% predicted

• Total bilirubin > 3 mg/dL

• Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic-pyruvic transaminase (SGPT) > 4 x upper limit of normal (ULN)

• Creatinine > 2 mg/dL and an estimated creatinine clearance < 40 mL/min

• Poorly-controlled hypertension despite multiple antihypertensive medications

• Karnofsky Performance Status (KPS) < 60%

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• B-cell Lymphoma
• Chronic Lymphocytic Leukemia
• Chronic Myelomonocytic Leukemia
• Hodgkin Lymphoma
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• Lymphoma
• Myelodysplastic Syndromes
• Myeloproliferative Disorder
• Myeloproliferative Disorders
• Non Hodgkin Lymphoma
• T-cell Lymphoma

Intervention

Radiation:
• Total body irradiation (TBI)
Administer Total body irradiation (TBI) 80 cGy on Day 1 of standard TLI ATG conditioning

Drug:
• Anti-thymocyte globulin (ATG)
Given intravenous (IV), Dose 1.5 mg/kg x 5 days
• Tacrolimus
Oral, Dose 0.05 mg/kg twice daily, can be given intravenous (IV)
• Mycophenolate mofetil (MMF)
Given Oral, 15 mg/k every 2 hours for peripheral blood stem cells (PBSC) from matched related donors; 15 mg/kg every 8 hours for PBSC from unrelated donors (URDs) or mismatched related donors.

Radiation:
• Total lymphoid irradiation (TLI)
9 x 120 cGy over 11 days

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, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Full-dose Donor Chimerism (FDC) at Day 28 Following TLI/ATG/TBI Conditioning.	Subsequent to TLI/ATG/TBI conditioning, the proportion of participants with full dose donor chimerism (FDC) will be determined by Day 28. FDC is defined as achieving = 95% donor type in the CD3+ lineage within 28 days of donor cell infusion, as assessed by short tandem repeat (STR) testing. The outcome will be expressed as the number of participants that achieve FDC by Day 28, a number without dispersion.	Day 28
Secondary	Disease Progression	Transplant recipients will be assessed for disease progression at 1 year after hematopoietic cell transplantation (HCT). The outcome is reported as the number of transplant recipients who experienced disease progression.	1 year
Secondary	Overall Survival (OS)	Overall survival (OS) is defined as the number of transplant recipients remaining alive at 12 months after transplant. The outcome is expressed as the number of transplant recipients who remained alive at 12 months after treatment, a number without dispersion.	1 year
Secondary	Event-free Survival (EFS) at 1 Year	Event-free survival (EFS) is defined as the number of transplant recipients remaining alive at 12 months after transplant and who did not experience disease relapse defined as blasts < 5%. The outcome is expressed as the number of transplant recipients remaining alive at 12 months after transplant without disease relapse, a number without dispersion.	1 year
Secondary	Non-relapse Mortality (NRM)	Non-relapse mortality (NRM) is defined as death without known disease relapse or recurrence. The outcome is expressed as the number of transplant recipients whose cause of death was not disease relapse or recurrence, a number without dispersion.	1 year
Secondary	Graft vs Host Disease (GvHD)	Recipients will be monitored for Grade 2 to 4 graft vs host disease (GvHD). The outcome is reported as the number of transplant recipients who experienced acute GvHD grades 2 to 4, the number of transplant recipients who experienced chronic and extensive GvHD. In addition, the number of transplant recipients with chronic and extensive GvHD that was refractory to treatment ("persistent") is reported. Per protocol, the result for chronic extensive and persistent GvHD is based on the subset of participants that had chronic and extensive GvHD.	1 year