Clinical trial NCT03734601: Total Body Irradiation +/- Total Lymphoid Irradiation & Anti-Thymocyte Globulin in Non-myeloablative Hematopoietic Cell Transplantation
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Myelodysplastic Syndromes
Myeloproliferative Disorder
Chronic Lymphocytic Leukemia
B-cell Lymphoma
T-cell Lymphoma
Non Hodgkin Lymphoma
Hodgkin Lymphoma
Chronic Myelomonocytic Leukemia
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2018-11-08
Enrollment: 22
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: 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)

Detailed 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.

Eligibility criteria: 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%

Primary outcomes:
measure: Full-dose Donor Chimerism (FDC) at Day 28 Following TLI/ATG/TBI Conditioning.
timeFrame: Day 28
Secondary outcomes:
measure: Disease Progression
timeFrame: 1 year
measure: Overall Survival (OS)
timeFrame: 1 year
measure: Event-free Survival (EFS) at 1 Year
timeFrame: 1 year
measure: Non-relapse Mortality (NRM)
timeFrame: 1 year
measure: Graft vs Host Disease (GvHD)
timeFrame: 1 year
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Robert Lowsky, MD
role: PRINCIPAL_INVESTIGATOR
References: