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

NCT ID: NCT03734601

Last Updated: 2023-12-12

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

22 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-11-05

Study Completion Date

2020-11-17

Brief Summary

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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

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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.

Conditions

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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TBI+TLI

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)

Group Type EXPERIMENTAL

Total body irradiation (TBI)

Intervention Type RADIATION

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

Anti-thymocyte globulin (ATG)

Intervention Type DRUG

Given intravenous (IV), Dose 1.5 mg/kg x 5 days

Tacrolimus

Intervention Type DRUG

Oral, Dose 0.05 mg/kg twice daily, can be given intravenous (IV)

Mycophenolate mofetil (MMF)

Intervention Type DRUG

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.

Total lymphoid irradiation (TLI)

Intervention Type RADIATION

9 x 120 cGy over 11 days

Interventions

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Total body irradiation (TBI)

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

Intervention Type RADIATION

Anti-thymocyte globulin (ATG)

Given intravenous (IV), Dose 1.5 mg/kg x 5 days

Intervention Type DRUG

Tacrolimus

Oral, Dose 0.05 mg/kg twice daily, can be given intravenous (IV)

Intervention Type DRUG

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.

Intervention Type DRUG

Total lymphoid irradiation (TLI)

9 x 120 cGy over 11 days

Intervention Type RADIATION

Other Intervention Names

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Fujimycin Cellcept MMF

Eligibility Criteria

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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%
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Stanford University

OTHER

Sponsor Role lead

Responsible Party

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Robert Lowsky

Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Robert Lowsky, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

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Stanford University School of Medicine

Stanford, California, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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BMT330

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-47407

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-47407

Identifier Type: -

Identifier Source: org_study_id