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

Primary Purpose

Acute Myeloid Leukemia, Myelodysplastic Syndromes, Myeloproliferative Disorder

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Total body irradiation (TBI)
Anti-thymocyte globulin (ATG)
Tacrolimus
Mycophenolate mofetil (MMF)
Total lymphoid irradiation (TLI)
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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%

Sites / Locations

  • Stanford University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TBI+TLI

Arm 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)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.

Full Information

First Posted
November 6, 2018
Last Updated
May 17, 2021
Sponsor
Stanford University
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1. Study Identification

Unique Protocol Identification Number
NCT03734601
Brief Title
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

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
November 5, 2018 (Actual)
Primary Completion Date
December 26, 2019 (Actual)
Study Completion Date
November 17, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Myelodysplastic Syndromes, Myeloproliferative Disorder, Chronic Lymphocytic Leukemia, B-cell Lymphoma, T-cell Lymphoma, Non Hodgkin Lymphoma, Hodgkin Lymphoma, Chronic Myelomonocytic Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
TBI+TLI
Arm Type
Experimental
Arm 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)
Intervention Type
Radiation
Intervention Name(s)
Total body irradiation (TBI)
Intervention Description
Administer Total body irradiation (TBI) 80 cGy on Day 1 of standard TLI ATG conditioning
Intervention Type
Drug
Intervention Name(s)
Anti-thymocyte globulin (ATG)
Intervention Description
Given intravenous (IV), Dose 1.5 mg/kg x 5 days
Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Other Intervention Name(s)
Fujimycin
Intervention Description
Oral, Dose 0.05 mg/kg twice daily, can be given intravenous (IV)
Intervention Type
Drug
Intervention Name(s)
Mycophenolate mofetil (MMF)
Other Intervention Name(s)
Cellcept, MMF
Intervention Description
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
Radiation
Intervention Name(s)
Total lymphoid irradiation (TLI)
Intervention Description
9 x 120 cGy over 11 days
Primary Outcome Measure Information:
Title
Full-dose Donor Chimerism (FDC) at Day 28 Following TLI/ATG/TBI Conditioning.
Description
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.
Time Frame
Day 28
Secondary Outcome Measure Information:
Title
Disease Progression
Description
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.
Time Frame
1 year
Title
Overall Survival (OS)
Description
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.
Time Frame
1 year
Title
Event-free Survival (EFS) at 1 Year
Description
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.
Time Frame
1 year
Title
Non-relapse Mortality (NRM)
Description
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.
Time Frame
1 year
Title
Graft vs Host Disease (GvHD)
Description
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.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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%
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Lowsky, MD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University School of Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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