GVHD - Graft-Versus-Host DiseasePhase 1/2NCT07675174
PTCy, Bortezomib and Sitagliptin for Prevention of GvHD Following Allogeneic HSCT
A Phase 1/2 study testing Post transplant cyclophosphamide, bortezomib and sitagliptin in 3+3 design to MTD in people with GVHD - Graft-Versus-Host Disease, run by Northwell Health at 1 site in United States.
Trial summary
Phase I-II studying post transplant cyclophosphamide, bortezomib and sitagliptin for GvHD prevention in allogeneic HSCT. Adults with hematologic malignancies undergoing an RIC allogeneic PBSC transplant from a 5/6 or 6/6 sibling or 7/8 or 8/8 matched unrelated donor. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- GVHD - Graft-Versus-Host Disease
- What is being tested?
- Post transplant cyclophosphamide, bortezomib and sitagliptin in 3+3 design to MTD
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Aug 2026to 1 Jul 2032
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with any of the following hematologic malignancies:
- AML in first remission (CR1) if they have intermediate- or high-risk cytogenetic and/or molecular features, or patients in second or subsequent complete remission (CR2, CR3, etc.). Complete remission is defined as presence of <5% blasts in the bone marrow with no morphological evidence of leukemia. Patients in CR with incomplete count recovery may be included.
- ALL with any of the following in CR1 or subsequent complete remission (CR2, CR3, etc.). Complete remission is defined as presence of <5% blasts in the bone marrow with no morphological evidence of leukemia. Patients in CR with incomplete count recovery may be included.
- MDS with a revised International Prognostic System Score (IPSS-R) of greater than 3 at diagnosis. Patients must have <10% blasts in the bone marrow documented within 30 days of transplant.*
- Therapy-related myelodysplastic disorder (t-MDS). Patients must have <10% blasts in the bone marrow documented within 30 days of transplant.*
- CMML type 1 or 2. Patients must have <10% blasts in the bone marrow documented within 30 days of transplant.* *Patients with MDS, t-MDS, and CMML will be included only in the phase I portion of the study.
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- Patient age ≥ 18 years
- KPS ≥70%
- Patients must also be suitable to receive an RIC regimen at the discretion of the treating physician. While there are not universally accepted or validated cut-off criteria of age, performance status, or HCT-CI for suitability for RIC, RIC transplants should be considered for patients 60 years and older and for patients <60 years who are "less fit" (e.g., KPS <90% and/or HCT-CI ≥3 due to lower non-relapse mortality associated with RIC).
- Patients receiving allogeneic PBSC grafts from HLA-matched (5/6 and 6/6 matches) siblings or matched unrelated donors (7/8 or 8/8 matches at HLA-A, B, C, DRB1 by high resolution typing) are included. All grafts will be unmanipulated (i.e., no T cell depleted or CD34 selected grafts). In addition, donors should meet institutional criteria for donation of PBSC, as well as the screening and eligibility criteria of the (NMDP) for unrelated donors, and the requirements of the United States Food and Drug Administration for HCT/P (21 CFR Part 1271).
- Required baseline laboratory values within 16 days prior to admission:
- Estimated creatinine clearance >60 mL/min/1.72 m2
- Serum total bilirubin ≤2 x upper limit of normal value (except for Gilbert's disease)
- AST and ALT ≤3 x upper limit of normal value
- ALP ≤250 IU/l
- Required baseline values within 60 days prior to admission:
- LVEF >40%
- Adjusted carbon monoxide diffusing capacity (DLCO) >50%
- No evidence of HIV infection (patients with immune dysfunction are at a significantly higher risk of infection from intensive immunosuppressive therapies)
- Non-pregnant and non-nursing
- Signed written informed consent (patient must be capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent)
- Patients must otherwise fulfill institutional criteria for eligibility to undergo reduced-intensity allogeneic stem cell transplantation
Who cannot join
- Pregnant or nursing females or women of reproductive capability who are unwilling to completely abstain from heterosexual sex or practice effective methods of contraception from start of conditioning through a minimum of 90 days after the last dose of study drug. A woman of reproductive capability is one who has not undergone a hysterectomy (removal of the womb), has not had both ovaries removed, or has not been post-menopausal (stopped menstrual periods) for more than 24 consecutive months.
- Male subjects who refuse to practice effective barrier contraception from the start of conditioning through a minimum of 90 days after the last dose of study drug, or completely abstain from heterosexual intercourse. This must be done even if they are surgically sterilized (i.e., post- vasectomy).
- Inability to provide informed consent.
- Patient had myocardial infarction within 6 months prior to enrollment or has NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant.
- Patients with active central nervous system leukemia
- Prior allogeneic HSCT or an autologous HSCT in past 12 months
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- Patients with diabetes mellitus requiring insulin secretagogues and/or insulin at time of enrollment
- Patients with a history of pancreatitis
- Patients with symptomatic cholelithiasis
- Known hypersensitivity to any of the components of the investigational treatment regimen
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study
- Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma, an in-situ malignancy, or low-risk prostate cancer after curative therapy
- Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial, and throughout the duration of this trial
- Prisoners
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Northwell Health
New Hyde Park, New York, 11040
Kelli Cole, MSN, FNP-BC, 15167348973, kcole5@northwell.edu
About this study
Official title: A Phase I-II Study of High-Dose Post-Transplant Cyclophosphamide, Bortezomib, and Abatacept for the Prevention of Graft-versus-Host Disease (GvHD) Following Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Phase I-II studying post transplant cyclophosphamide, bortezomib and sitagliptin for GvHD prevention in allogeneic HSCT. Adults with hematologic malignancies undergoing an RIC allogeneic PBSC transplant from a 5/6 or 6/6 sibling or 7/8 or 8/8 matched unrelated donor.
Read the detailed description
The phase I portion of the clinical trial, which will define the MTD of sitagliptin, bortezomib, and PTCy as GvHD prophylaxis after reduced-intensity allogeneic PBSC transplantation. Dose escalation will follow a traditional 3+3 design. We will first test the drugs at full doses and sequentially de-escalate the doses of sitagliptin, and then bortezomib, in successive cohorts if a DLT is observed using a 3+3 design.
The phase II portion is an open-label, single-arm, Simon two-stage minimax phase II trial design.
Patients will receive RIC with fludarabine, busulfan (rATG in unrelated donor grafts) in preparation for allogeneic hematopoietic PBSC transplant from a 5/6 or 6/6 sibling donor or 7/8 or 8/8 matched unrelated donor. Patients will receive GvHD prophylaxis with sitagliptin, bortezomib, and high-dose PTCy.
- Conditions
- GVHD - Graft-Versus-Host Disease
- Being tested
- Post transplant cyclophosphamide, bortezomib and sitagliptin in 3+3 design to MTD
- Keywords
- GvHD, Allogeneic Transplant, Post transplant cyclophosphamide, Sitagliptin, Bortezomib
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Post transplant cyclophosphamide, bortezomib and sitagliptin in 3+3 design to MTDDrug
Interventional, non-randomized, open-label, phase I/II study. Phase I: 3+3 phase dose de-escalation; phase II: Simon two-stage minimax.
| Study group | Role | What they receive |
|---|---|---|
| Dose Level -2 | Experimental | Dosing for MTD: PTCy 50 mg/kg (day +3, +4), bortezomib 1 mg/m2 (day 0, +3), sitagliptin 400 mg (every 12 hours. day -1 to day +14) Receives: Drug: Post transplant cyclophosphamide, bortezomib and sitagliptin in 3+3 design to MTD |
| Dose Level -1 | Experimental | Dosing for MTD: PTCy 50 mg/kg (day +3, +4), bortezomib 1.3 mg/m2 (day 0, +3), sitagliptin 400 mg (every 12 hours. day -1 to day +14) Receives: Drug: Post transplant cyclophosphamide, bortezomib and sitagliptin in 3+3 design to MTD |
| Dose Level 1 | Experimental | Dosing for MTD: PTCy 50 mg/kg (day +3, +4), bortezomib 1.3 mg/m2 (day 0, +3), sitagliptin 600 mg (every 12 hours. day -1 to day +14) Receives: Drug: Post transplant cyclophosphamide, bortezomib and sitagliptin in 3+3 design to MTD |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I - Dose Limiting Toxicity
GvHD prophylaxis with a set dose of Post Transplant Cyclophosphamide and Bortezomib will be given in the post-transplant setting. The Sitagliptin dosing will be escalated in a 3+3 design to determine maximum tolerated dose. The dose established in phase I will be adopted for the phase II portion.
Measured: Day +30 post transplant determination
Phase II - acute GvHD post-transplant in evaluable participants
The phase II portion will evaluate the incidence of grades II-IV acute GvHD post-transplant through day +100. This incidence will be compared against historical controls.
Measured: Day 100 after allogeneic hematopoietic stem cell transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2026
- Study start14 Aug 2026
- Primary completion1 Jul 2030 (estimated)
- Study completion1 Jul 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GVHD - Graft-Versus-Host DiseaseStudies of the same condition, open and under way.
- More trials run by Northwell HealthThe 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 1/2
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Northwell Health
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ahmad Samer Al-Homsi, Northwell Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07675174
- Sponsor's protocol ID
- 24-0385; 24-003
- Status last verified
- Oct 2026
- First submitted
- 23 Jun 2026
- Last updated
- 6 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I-II Study of High-Dose Post-Transplant Cyclophosphamide, Bortezomib, and Abatacept for the Prevention of Graft-versus-Host Disease (GvHD) Following Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
- ClinicalTrials.gov ID
- NCT07675174
- Acronym / sponsor ID
- 24-0385; 24-003
- Conditions
- GVHD - Graft-Versus-Host Disease
- Keywords
- GvHD, Allogeneic Transplant, Post transplant cyclophosphamide, Sitagliptin, Bortezomib
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- Northwell HealthUniversity, hospital or other
- Study start
- 14 Aug 2026 (actual)
- Primary completion
- 1 Jul 2030 (estimated)
- Study completion
- 1 Jul 2032 (estimated)
- First posted
- 30 Jun 2026 (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.
Phase I-II studying post transplant cyclophosphamide, bortezomib and sitagliptin for GvHD prevention in allogeneic HSCT. Adults with hematologic malignancies undergoing an RIC allogeneic PBSC transplant from a 5/6 or 6/6 sibling or 7/8 or 8/8 matched unrelated donor.
Detailed description
The phase I portion of the clinical trial, which will define the MTD of sitagliptin, bortezomib, and PTCy as GvHD prophylaxis after reduced-intensity allogeneic PBSC transplantation. Dose escalation will follow a traditional 3+3 design. We will first test the drugs at full doses and sequentially de-escalate the doses of sitagliptin, and then bortezomib, in successive cohorts if a DLT is observed using a 3+3 design.
The phase II portion is an open-label, single-arm, Simon two-stage minimax phase II trial design.
Patients will receive RIC with fludarabine, busulfan (rATG in unrelated donor grafts) in preparation for allogeneic hematopoietic PBSC transplant from a 5/6 or 6/6 sibling donor or 7/8 or 8/8 matched unrelated donor. Patients will receive GvHD prophylaxis with sitagliptin, bortezomib, and high-dose PTCy.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dose Level -2 | Experimental | Drug: Post transplant cyclophosphamide, bortezomib and sitagliptin in 3+3 design to MTDDosing for MTD: PTCy 50 mg/kg (day +3, +4), bortezomib 1 mg/m2 (day 0, +3), sitagliptin 400 mg (every 12 hours. day -1 to day +14) |
| Dose Level -1 | Experimental | Drug: Post transplant cyclophosphamide, bortezomib and sitagliptin in 3+3 design to MTDDosing for MTD: PTCy 50 mg/kg (day +3, +4), bortezomib 1.3 mg/m2 (day 0, +3), sitagliptin 400 mg (every 12 hours. day -1 to day +14) |
| Dose Level 1 | Experimental | Drug: Post transplant cyclophosphamide, bortezomib and sitagliptin in 3+3 design to MTDDosing for MTD: PTCy 50 mg/kg (day +3, +4), bortezomib 1.3 mg/m2 (day 0, +3), sitagliptin 600 mg (every 12 hours. day -1 to day +14) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Patients with any of the following hematologic malignancies:
- Patient age ≥ 18 years
- KPS ≥70%
- Patients must also be suitable to receive an RIC regimen at the discretion of the treating physician. While there are not universally accepted or validated cut-off criteria of age, performance status, or HCT-CI for suitability for RIC, RIC transplants should be considered for patients 60 years and older and for patients <60 years who are "less fit" (e.g., KPS <90% and/or HCT-CI ≥3 due to lower non-relapse mortality associated with RIC).
- Patients receiving allogeneic PBSC grafts from HLA-matched (5/6 and 6/6 matches) siblings or matched unrelated donors (7/8 or 8/8 matches at HLA-A, B, C, DRB1 by high resolution typing) are included. All grafts will be unmanipulated (i.e., no T cell depleted or CD34 selected grafts). In addition, donors should meet institutional criteria for donation of PBSC, as well as the screening and eligibility criteria of the (NMDP) for unrelated donors, and the requirements of the United States Food and Drug Administration for HCT/P (21 CFR Part 1271).
Key exclusion criteria (14 listed)
- Pregnant or nursing females or women of reproductive capability who are unwilling to completely abstain from heterosexual sex or practice effective methods of contraception from start of conditioning through a minimum of 90 days after the last dose of study drug. A woman of reproductive capability is one who has not undergone a hysterectomy (removal of the womb), has not had both ovaries removed, or has not been post-menopausal (stopped menstrual periods) for more than 24 consecutive months.
- Male subjects who refuse to practice effective barrier contraception from the start of conditioning through a minimum of 90 days after the last dose of study drug, or completely abstain from heterosexual intercourse. This must be done even if they are surgically sterilized (i.e., post- vasectomy).
- Inability to provide informed consent.
- Patient had myocardial infarction within 6 months prior to enrollment or has NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant.
- Patients with active central nervous system leukemia
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 |
|---|---|---|
| Post transplant cyclophosphamide, bortezomib and sitagliptin in 3+3 design to MTDInterventional, non-randomized, open-label, phase I/II study. Phase I: 3+3 phase dose de-escalation; phase II: Simon two-stage minimax. | Drug | Dose Level -1, Dose Level -2, Dose Level 1 |
Primary outcome
Phase I - Dose Limiting Toxicity
Time frame: Day +30 post transplant determination
GvHD prophylaxis with a set dose of Post Transplant Cyclophosphamide and Bortezomib will be given in the post-transplant setting. The Sitagliptin dosing will be escalated in a 3+3 design to determine maximum tolerated dose. The dose established in phase I will be adopted for the phase II portion.
Phase II - acute GvHD post-transplant in evaluable participants
Time frame: Day 100 after allogeneic hematopoietic stem cell transplantation
The phase II portion will evaluate the incidence of grades II-IV acute GvHD post-transplant through day +100. This incidence will be compared against historical controls.
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 6 Nov 2026.
- Individual participant dataSharing planned: Yes
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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.
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 Post transplant cyclophosphamide, bortezomib and sitagliptin in 3+3 design to MTD in people with GVHD - Graft-Versus-Host Disease, run by Northwell Health 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 22 inclusion and 14 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 6 Nov 2026. 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 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 Kelli Cole, MSN, FNP-BC (15167348973, kcole5@northwell.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I - Dose Limiting Toxicity (time frame: Day +30 post transplant determination). The study lists 2 primary outcomes in all. 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 6 Nov 2026.