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

Stanford University

Status and phase: Completed; Phase 2

Conditions: Hodgkin Lymphoma; T-cell Lymphoma; B-cell Lymphoma; Chronic Lymphocytic Leukemia; Non Hodgkin Lymphoma; Myelodysplastic Syndromes; Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia; Myeloproliferative Disorder

Treatments: Radiation: Total lymphoid irradiation (TLI); Drug: Anti-thymocyte globulin (ATG); Drug: Mycophenolate mofetil (MMF); Radiation: Total body irradiation (TBI); Drug: Tacrolimus

Study type: Interventional

Funder types: Other

Identifiers

NCT03734601

BMT330 (Other Identifier)

IRB-47407 (Other Identifier)

Details and patient eligibility

About

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)

Full 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.

Enrollment: 22 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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%

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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22 participants in 1 patient group

TBI+TLI

Experimental group

Description:

TBI, single exposure on Day -1, 80 centigray (cGy) in addition to total lymphoid irradiation (TLI, 120 cGy/day for 9 days, weekends excluded) and anti-thymocyte globulin (ATG) 1.5 mg/kg (conditioning regimen)

Treatment:

Drug: Tacrolimus

Drug: Mycophenolate mofetil (MMF)

Radiation: Total body irradiation (TBI)

Radiation: Total lymphoid irradiation (TLI)

Drug: Anti-thymocyte globulin (ATG)