Acute Myeloid LeukemiaPhase 2NCT03734601
Total Body Irradiation +/- Total Lymphoid Irradiation & Anti-Thymocyte Globulin in Non-myeloablative Hematopoietic Cell Transplantation
A Phase 2 study testing Total body irradiation (TBI), Anti-thymocyte globulin (ATG) and Tacrolimus in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by Stanford University at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Myelodysplastic Syndromes, Myeloproliferative Disorder
- What is being tested?
- Total body irradiation (TBI), Anti-thymocyte globulin (ATG) and Tacrolimus
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Nov 2018to 17 Nov 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 15Show fewer
- 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 locations and contacts
1 site in 1 country.
United States1 site
Stanford University School of Medicine
Stanford, California, 94305
About this study
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
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)
Read the 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.
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndromes, Myeloproliferative Disorder, Chronic Lymphocytic Leukemia, B-cell Lymphoma, T-cell Lymphoma
- Being tested
- Total body irradiation (TBI), Anti-thymocyte globulin (ATG), Tacrolimus, Mycophenolate mofetil (MMF), Total lymphoid irradiation (TLI)
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Myeloproliferative Disorders, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, B-Cell, Lymphoma, T-Cell, Lymphoma, Non-Hodgkin, Hodgkin Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Total body irradiation (TBI)Radiation
Administer Total body irradiation (TBI) 80 cGy on Day 1 of standard TLI ATG conditioning
Anti-thymocyte globulin (ATG)Drug
Given intravenous (IV), Dose 1.5 mg/kg x 5 days
TacrolimusDrug
Also called Fujimycin
Oral, Dose 0.05 mg/kg twice daily, can be given intravenous (IV)
Mycophenolate mofetil (MMF)Drug
Also called Cellcept, 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.
Total lymphoid irradiation (TLI)Radiation
9 x 120 cGy over 11 days
| Study group | Role | What they receive |
|---|---|---|
| TBI+TLI | Experimental | 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) Receives: Radiation: Total body irradiation (TBI); Drug: Anti-thymocyte globulin (ATG); Drug: Tacrolimus; Drug: Mycophenolate mofetil (MMF); Radiation: Total lymphoid irradiation (TLI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 28
Secondary outcomes (5)
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.
Measured: 1 year
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.
Measured: 1 year
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.
Measured: 1 year
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.
Measured: 1 year
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.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2018
- Study start5 Nov 2018
- Primary completion26 Dec 2019
- Study completion17 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Robert Lowsky, Stanford University
- Investigators
- Robert Lowsky, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03734601
- Sponsor's protocol ID
- IRB-47407
- Other IDs
- BMT330, IRB-47407
- Status last verified
- May 2021
- First submitted
- 6 Nov 2018
- Last updated
- 12 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03734601
- Acronym / sponsor ID
- IRB-47407
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndromes, Myeloproliferative Disorder, Chronic Lymphocytic Leukemia, B-cell Lymphoma, T-cell Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- 5 Nov 2018 (actual)
- Primary completion
- 26 Dec 2019 (actual)
- Study completion
- 17 Nov 2020 (actual)
- First posted
- 8 Nov 2018 (actual)
- Results
- Posted 11 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TBI+TLI | Experimental | Radiation: Total body irradiation (TBI), Drug: Anti-thymocyte globulin (ATG), Drug: Tacrolimus, Drug: Mycophenolate mofetil (MMF), Radiation: Total lymphoid irradiation (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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Total body irradiation (TBI)Administer Total body irradiation (TBI) 80 cGy on Day 1 of standard TLI ATG conditioning | Radiation | TBI+TLI |
| Anti-thymocyte globulin (ATG)Given intravenous (IV), Dose 1.5 mg/kg x 5 days | Drug | TBI+TLI |
| TacrolimusAlso: FujimycinOral, Dose 0.05 mg/kg twice daily, can be given intravenous (IV) | Drug | TBI+TLI |
| Mycophenolate mofetil (MMF)Also: Cellcept, MMFGiven 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. | Drug | TBI+TLI |
| Total lymphoid irradiation (TLI)9 x 120 cGy over 11 days | Radiation | TBI+TLI |
Primary outcome
Full-dose Donor Chimerism (FDC) at Day 28 Following TLI/ATG/TBI Conditioning.
Time frame: Day 28
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.
5 secondary outcomes
Disease Progression
Time frame: 1 year
Overall Survival (OS)
Time frame: 1 year
Event-free Survival (EFS) at 1 Year
Time frame: 1 year
Non-relapse Mortality (NRM)
Time frame: 1 year
Graft vs Host Disease (GvHD)
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Lowsky, MD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Total body irradiation (TBI), Anti-thymocyte globulin (ATG) and Tacrolimus in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by Stanford University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Full-dose Donor Chimerism (FDC) at Day 28 Following TLI/ATG/TBI Conditioning. (time frame: Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2023.