Acute Myeloid LeukemiaPhase 1/2NCT06299462
PTCy and ATG for MSD and MUD Transplants
A Phase 1/2 study testing ATG 5.0, Cyclophosphamide injection and ATG 4.0 in people with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia, run by Instituto Nacional de Cancer, Brazil at 1 site in Brazil.
Trial summary
Hematopoietic stem cell transplantation is a curative treatment for a number of benign and malignant hematologic diseases. One of the key parts of hematopoietic stem cell transplantation is the prophylaxis of graft-versus-host disease. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndromes
- What is being tested?
- ATG 5.0, Cyclophosphamide injection and ATG 4.0
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteBrazil
- Study dates
- 14 Jun 2024to 1 Jun 2031
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Patient with (1) acute leukemia in first or second remission; (2) myelodysplasia with less than 20% blasts; (3) Hodgkin's or non-Hodgkin's lymphoma, in partial remission after salvage therapy
- Who will receive a related or unrelated, HLA-compatible transplant;
- Who is a transplant candidate with FluMel, FluTBI, CyTBI, BuCy or BuFlu conditioning;
- Peripheral blood source;
- Age between 18 and 60 years.
Who cannot join
- Hepatic dysfunction (transaminases x2 the normal value)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Brazil1 site, 1 recruiting
- Recruiting
Instituto Nacional de Cancer
Rio de Janeiro, Rio de Janeiro, 20230-130
Leonardo J Arcuri, MD, +55(21)3207-1304, leonardojavier@gmail.com
Simone Lermontov, +55(21)3207-1261, simonelermontov@globo.com
About this study
Official title: Efficacy Evaluation of Post-transplant Cyclophosphamide-based Graft-versus-host Disease Prophylaxis with ATG, Calcineurin Inhibitor-free, for Matched-sibling or Matched-unrelated Transplantation
Hematopoietic stem cell transplantation is a curative treatment for a number of benign and malignant hematologic diseases. One of the key parts of hematopoietic stem cell transplantation is the prophylaxis of graft-versus-host disease. Since the end of the 1970s, with the introduction of cyclosporine, calcineurin inhibitors (cyclosporine and tacrolimus) have become part of almost all prophylactic regimens, even though they are a group of drugs with a poor toxicity profile that requires monitoring. constant serum level. Since 2008, post-transplant cyclophosphamide has been introduced with great success, associated with a calcineurin inhibitor and mycophenolate, in the prophylaxis of graft-versus-host disease in haploidentical transplantation (50% matched).
Since then, in view of this enormous success, efforts have been made to incorporate post-transplant cyclophosphamide in matched related and unrelated transplants, or with a mismatch.
Read more
This is a prospective, 2-arm, non-randomized study. Arm 1, with related donors, and arm 2, with unrelated donors. Patients will be allocated in these arms according to donor availability (patients with a matched-sibling donor will receive a matched-sibling transplant; patients with no related donors but with unrelated donors, an unrelated transplant).
Patients who are ready for transplantation with matched-sibling or unrelated donors will be recruited to participate in the study.
The stem cell collection target will be 5E6 CD34/kg recipient weight for peripheral source. If a quantity greater than this is collected, the remainder will be cryopreserved according to the institutional protocol.
Graft-versus-host disease prophylaxis will be performed on D+3 and D+4 with cyclophosphamide and with ATG on D-3 and D-2 for matched-sibling or unrelated donors transplants.
- Conditions
- Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndromes, Hodgkin Lymphoma, Non-hodgkin Lymphoma
- Being tested
- ATG 5.0, Cyclophosphamide injection, ATG 4.0
- Keywords
- posttransplant cyclophosphamide, ATG, calcineurin-free GVHD prophylaxis, graft-versus-host disease
- Medical subject headings
- Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Myelodysplastic Syndromes, Hodgkin Disease, Lymphoma, Non-Hodgkin, Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ATG 5.0Drug
ATG 2.5 mg/kg on days -3 and -2
Cyclophosphamide injectionDrug
Cyclophosphamide 50 mg/kg on days +3 and +4
ATG 4.0Drug
ATG 2.5 mg/kg on day -2 + 1.5 mg/kg on day -3
| Study group | Role | What they receive |
|---|---|---|
| Matched-sibling donor transplants | Experimental | Matched sibling transplants will receive PTCy + ATG4.0 Receives: Drug: Cyclophosphamide injection; Drug: ATG 4.0 |
| Matched unrelated donor transplants | Experimental | Unrelated transplants will receive PTCy + ATG5.0 Receives: Drug: ATG 5.0; Drug: Cyclophosphamide injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative incidence of grades III-IV acute GVHD by the MAGIC criteria
Cumulative incidence of acute graft-versus-host disease, grades III-IV by the MAGIC criteria
Measured: 6 months
Secondary outcomes (12)
Cumulative incidence of grades II-IV acute GVHD by the MAGIC criteria
Cumulative incidence of acute graft-versus-host disease, grades II-IV by the MAGIC criteria
Measured: 6 months
Cumulative incidence of steroid-refractory acute GVHD as defined by Mohty et al PMID 32756949
Cumulative incidence of steroid-refractory graft-versus-host disease
Measured: 6 months
Cumulative incidence of chronic GVHD as defined by the NIH criteria
Cumulative incidence of chronic graft-versus-host disease
Measured: 3 years
Cumulative incidence of steroid-requiring chronic GVHD as defined by the NIH criteria
Cumulative incidence of steroid-requiring chronic graft versus host disease
Measured: 3 years
Cumulative incidence of non-relapse mortality, i.e., death not following disease relapse
Cumulative incidence of death not caused by primary malignant disease or following relapse
Measured: 3 years
Cumulative incidence of relapse, defined as > 5% blasts in bone marrow or 1% blasts in peripheral blood (acute leukemias/myelodysplasia) or biopsy proven relapse or positve PET-CT (lymphoma)
Cumulative incidence of relapse of primary malignant disease
Measured: 3 years
Rate of overall survival
Death by any cause
Measured: 3 years
Rate of disease-free survival (death or relapse)
Composite outcome of death or primary disease relapse
Measured: 3 years
Cumulative incidence of clinically significant CMV reactivation (which led to antiviral treatment)
Incidence of cytomegalovirus reactivation
Measured: 3 year
Cumulative incidence of posttransplant lymphoproliferative disorder (biopsy-proven or positive EBV PCR combined with clinical symptoms)
Incidence of posttransplant lymphoproliferative disorder
Measured: 3 years
Cumulative incidence CMV disease (biopsy-proven CMV disease OR suggestive CMV+ BAL)
Cumulative incidence of cytomegalovirus disease
Measured: 3 years
Measuremnt of quality of life using the FACT-BMT scale
Measurement quality of life
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2024
- Study start14 Jun 2024
- Primary completion1 Jun 2031 (estimated)
- Study completion1 Jun 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Patients with a matched sibling donor will be assigned to the PTCy+ATG4.l0 arm, while patients with a matched unrelated donor will be assigned to the PTCy+ATG5.0 arm
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Instituto Nacional de Cancer, Brazil
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Leonardo J Arcuri, MD, PhD, Principal investigator, Instituto Nacional de Cancer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06299462
- Sponsor's protocol ID
- PTCy-ATG-001
- Status last verified
- Mar 2024
- First submitted
- 13 Mar 2023
- Last updated
- 25 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Upon finalization of the study, data will be shared on reasonable requests.
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy Evaluation of Post-transplant Cyclophosphamide-based Graft-versus-host Disease Prophylaxis with ATG, Calcineurin Inhibitor-free, for Matched-sibling or Matched-unrelated Transplantation
- ClinicalTrials.gov ID
- NCT06299462
- Acronym / sponsor ID
- PTCy-ATG-001
- Conditions
- Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndromes, Hodgkin Lymphoma, Non-hodgkin Lymphoma
- Keywords
- posttransplant cyclophosphamide, ATG, calcineurin-free GVHD prophylaxis, graft-versus-host disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Instituto Nacional de Cancer, BrazilOther government
- Study start
- 14 Jun 2024 (actual)
- Primary completion
- 1 Jun 2031 (estimated)
- Study completion
- 1 Jun 2031 (estimated)
- First posted
- 7 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hematopoietic stem cell transplantation is a curative treatment for a number of benign and malignant hematologic diseases. One of the key parts of hematopoietic stem cell transplantation is the prophylaxis of graft-versus-host disease. Since the end of the 1970s, with the introduction of cyclosporine, calcineurin inhibitors (cyclosporine and tacrolimus) have become part of almost all prophylactic regimens, even though they are a group of drugs with a poor toxicity profile that requires monitoring. constant serum level. Since 2008, post-transplant cyclophosphamide has been introduced with great success, associated with a calcineurin inhibitor and mycophenolate, in the prophylaxis of graft-versus-host disease in haploidentical transplantation (50% matched).
Since then, in view of this enormous success, efforts have been made to incorporate post-transplant cyclophosphamide in matched related and unrelated transplants, or with a mismatch.
This is a prospective, 2-arm, non-randomized study. Arm 1, with related donors, and arm 2, with unrelated donors. Patients will be allocated in these arms according to donor availability (patients with a matched-sibling donor will receive a matched-sibling transplant; patients with no related donors but with unrelated donors, an unrelated transplant).
Patients who are ready for transplantation with matched-sibling or unrelated donors will be recruited to participate in the study.
The stem cell collection target will be 5E6 CD34/kg recipient weight for peripheral source. If a quantity greater than this is collected, the remainder will be cryopreserved according to the institutional protocol.
Graft-versus-host disease prophylaxis will be performed on D+3 and D+4 with cyclophosphamide and with ATG on D-3 and D-2 for matched-sibling or unrelated donors transplants.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Patients with a matched sibling donor will be assigned to the PTCy+ATG4.l0 arm, while patients with a matched unrelated donor will be assigned to the PTCy+ATG5.0 arm
| Arm | Type | Receives |
|---|---|---|
| Matched-sibling donor transplants | Experimental | Drug: Cyclophosphamide injection, Drug: ATG 4.0Matched sibling transplants will receive PTCy + ATG4.0 |
| Matched unrelated donor transplants | Experimental | Drug: ATG 5.0, Drug: Cyclophosphamide injectionUnrelated transplants will receive PTCy + ATG5.0 |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Patient with (1) acute leukemia in first or second remission; (2) myelodysplasia with less than 20% blasts; (3) Hodgkin's or non-Hodgkin's lymphoma, in partial remission after salvage therapy
- Who will receive a related or unrelated, HLA-compatible transplant;
- Who is a transplant candidate with FluMel, FluTBI, CyTBI, BuCy or BuFlu conditioning;
- Peripheral blood source;
- Age between 18 and 60 years.
Key exclusion criteria (1 listed)
- Hepatic dysfunction (transaminases x2 the normal value)
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 |
|---|---|---|
| ATG 5.0ATG 2.5 mg/kg on days -3 and -2 | Drug | Matched unrelated donor transplants |
| Cyclophosphamide injectionCyclophosphamide 50 mg/kg on days +3 and +4 | Drug | Matched unrelated donor transplants, Matched-sibling donor transplants |
| ATG 4.0ATG 2.5 mg/kg on day -2 + 1.5 mg/kg on day -3 | Drug | Matched-sibling donor transplants |
Primary outcome
Cumulative incidence of grades III-IV acute GVHD by the MAGIC criteria
Time frame: 6 months
Cumulative incidence of acute graft-versus-host disease, grades III-IV by the MAGIC criteria
12 secondary outcomes
Cumulative incidence of grades II-IV acute GVHD by the MAGIC criteria
Time frame: 6 months
Cumulative incidence of steroid-refractory acute GVHD as defined by Mohty et al PMID 32756949
Time frame: 6 months
Cumulative incidence of chronic GVHD as defined by the NIH criteria
Time frame: 3 years
Cumulative incidence of steroid-requiring chronic GVHD as defined by the NIH criteria
Time frame: 3 years
Cumulative incidence of non-relapse mortality, i.e., death not following disease relapse
Time frame: 3 years
Cumulative incidence of relapse, defined as > 5% blasts in bone marrow or 1% blasts in peripheral blood (acute leukemias/myelodysplasia) or biopsy proven relapse or positve PET-CT (lymphoma)
Time frame: 3 years
Rate of overall survival
Time frame: 3 years
Rate of disease-free survival (death or relapse)
Time frame: 3 years
Cumulative incidence of clinically significant CMV reactivation (which led to antiviral treatment)
Time frame: 3 year
Cumulative incidence of posttransplant lymphoproliferative disorder (biopsy-proven or positive EBV PCR combined with clinical symptoms)
Time frame: 3 years
Cumulative incidence CMV disease (biopsy-proven CMV disease OR suggestive CMV+ BAL)
Time frame: 3 years
Measuremnt of quality of life using the FACT-BMT scale
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2025.
- Individual participant dataSharing planned: Yes. Upon finalization of the study, data will be shared on reasonable requests.
Related trials for Acute Myeloid Leukemia
RecruitingObservational study
A Long-term Follow-up Study of Patients With ARD103 CAR-T Cell Therapies
Acute Myeloid Leukemia, in Relapse, Acute Myeloid Leukemia, in Relapsed or Refractory
RecruitingPhase 2
MYELOMATCH: A Screening Study to Assign People With Myeloid Cancer to a Treatment Study or Standard of Care Treatment Within myeloMATCH (MyeloMATCH Screening Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
RecruitingPhase 1
225Ac-DOTA-Anti-CD38 Daratumumab Monoclonal Antibody With Fludarabine, Melphalan and Total Marrow and Lymphoid Irradiation as Conditioning Treatment for Donor Stem Cell Transplant in Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia and Myelodysplastic Syndrome
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
RecruitingPhase 2
Testing the Addition of Venetoclax or Gemtuzumab Ozogamicin (GO) to Usual Treatment Regimen (Cytarabine and Daunorubicin, "7+3") for Core Binding Factor Acute Myeloid Leukemia (CBF-AML) to Improve Response (A MYELOMATCH Treatment Trial)
Core Binding Factor Acute Myeloid Leukemia
RecruitingPhase 1/2
Phase I/II Trial: Engineered Donor Graft (Orca Q) for Pediatric Hematopoietic Cell Transplant (HCT)
Acute Myeloid Leukemia, Acute Lymphoid Leukemia
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.
Leonardo J Arcuri, MD, PhD principal investigator
Instituto Nacional de Cancer
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ATG 5.0, Cyclophosphamide injection and ATG 4.0 in people with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia, run by Instituto Nacional de Cancer, Brazil at 1 site in Brazil.
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 5 inclusion and 1 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: looking for participants now, as of the sponsor's last update on 25 Feb 2025. 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 Brazil. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Leonardo J Arcuri, MD, PhD (+5521981334715, leonardojavier@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cumulative incidence of grades III-IV acute GVHD by the MAGIC criteria (time frame: 6 months). 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 25 Feb 2025.