Graft-versus-host DiseasePhase 1/2NCT05289167
Post-Transplant Cyclophosphamide, Bortezomib and Abatacept for the Prevention of Graft-versus-Host-Disease (GvHD)
A Phase 1/2 study testing Cyclophosphamide, Abatacept and Bortezomib in people with Graft-versus-host Disease, run by Northwell Health at 1 site in United States.
Trial summary
This is a phase I-II clinical trial. Adult subjects with hematological malignancies undergoing allogeneic HSCT from an HLA matched sibling or ≥7 out of 8 allele level HLA matched unrelated donor are eligible for the study if they meet the criteria defined in our standard operation procedures (SOPs), meet all inclusion… Read more about this study
- Who is it for?
- Ages 14 to 100 years
- Conditions the study is for
- Graft-versus-host Disease
- What is being tested?
- Cyclophosphamide, Abatacept and Bortezomib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Mar 2022to Aug 2028
- 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 14 to 100 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age ≥14 years
- Karnofsky score ≥70%
- No evidence of progressive bacterial, viral, or fungal infection
- Creatinine clearance >50 mL/min/1.72m2
- ALT and AST <3 x the upper limit of normal
- Total bilirubin <2 x the upper limit of normal (except for Gilbert's syndrome)
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- Alkaline phosphatase ≤250 IU/L
- Left Ventricular Ejection Fraction (LVEF) >45%
- Adjusted Carbon Monoxide Diffusing Capacity (DLCO) >50%
- Negative HIV serology
- Negative pregnancy test: Confirmation per negative serum β-human chorionic gonadotropin (β-hCG)
- Willing to comply with all study procedures and be available for the duration of the study.
Who cannot join
- Pregnant or nursing females or women of reproductive capability who are unwilling to completely abstain from heterosexual sex or practice 2 effective methods of contraception from start of conditioning through 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 months in a row.
- 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 New York Heart Association (NYHA) Class III or IV heart failure (see Appendix D), 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.
- Known allergies to any of the components of the investigational treatment regimen.
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
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- 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
- Pregnant women
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, 10016
Kelli Cole, 516-734-8973, kcole5@northwell.edu
Angie Fleury, 516-734-8973, AFleury2@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 Allogenic Hematopoietic Stem Cell Transplantation (HSCT)
This is a phase I-II clinical trial. Adult subjects with hematological malignancies undergoing allogeneic HSCT from an HLA matched sibling or ≥7 out of 8 allele level HLA matched unrelated donor are eligible for the study if they meet the criteria defined in our standard operation procedures (SOPs), meet all inclusion criteria, and do not satisfy any exclusion criteria. Subjects will receive a standard of care conditioning regimen. Subjects will receive investigational PTCy, investigational bortezomib and investigational abatacept as GvHD prophylaxis.
Read the detailed description
The study will have a phase I and phase II potions. The phase I portion will employ a 3+3 dose escalation design to define the maximum tolerated dose (MTD) of abatacept added to PTCy and bortezomib following HSCT. The phase II portion will consist of two single arm, open label, optimal 2-stage Simon design studies conducted in two separate strata for HLA matched and HLA mismatched donor transplants. Adult patients with hematological malignancies undergoing allogeneic HSCT from an HLA matched sibling or ≥7 out of 8 allele level HLA matched unrelated donor are eligible for the study if they meet the standard criteria defined in our institutional standard operation procedures (SOPs), meet all inclusion criteria, and do not satisfy any exclusion criteria. Subjects will receive a standard of care conditioning regimen followed by peripheral blood hematopoietic stem cells. Subjects with unrelated donors will also receive rabbit anti-thymocyte globulin (rATG). Subjects will receive investigational PTCy, investigational bortezomib and investigational abatacept as GvHD prophylaxis. The phase II portion dose of abatacept will be the MTD as determined in the phase I portion of the study. In the phase II portions, subjects will be stratified based on whether they receive a matched sibling or matched unrelated (matched) donor transplant and ≥7 out of 8, allele level matched (mismatched) unrelated donor transplant.
- Conditions
- Graft-versus-host Disease
- Being tested
- Cyclophosphamide, Abatacept, Bortezomib
- Keywords
- GvHD, post transplant cyclophosphamide, abatacept
- 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.
CyclophosphamideDrug
Also called Cytoxan®
37.5 mg/kg IV over 1 hour on Day +3 and +4
AbataceptDrug
Also called Orecia®
Dose level 0: 10 mg/kg IV over 30-60 minutes on day +5
Dose level 1: 10mg/kg IV over 30-60 minutes on day +5 and +14
Dose level 2: 10mg/kg IV over 30-60 minutes on day +5, +14, and +28
BortezomibDrug
Also called Velcade®
1.3 mg/m2 IV 6 hours after graft infusion completion and 72 hours thereafter.
| Study group | Role | What they receive |
|---|---|---|
| Participants with hematological malignancies | Experimental | Participants undergoing Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) will receive a combination of cyclophosphamide, known commercially as Cytoxan®, abatacept, known as Orecia® and bortezomib commercially known as Velcade®, to reduce the rate of graft-versus-host disease (GvHD). These medications will be given for GvHD prevention during the transplant process. Receives: Drug: Cyclophosphamide; Drug: Abatacept; Drug: Bortezomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I:Incidence Dose limiting toxicity (DLT)
Defined as grade 4 non-hematologic toxicity affecting the oral cavity, gastrointestinal tract, lung, heart, liver, kidney, bladder, or central nervous system.
Measured: Day+1 to Day +120
Phase II: Grades II-IV Acute GvHD
The first day of grades II-IV acute GvHD will be recorded for that grade. This end point will be evaluated through day +120 post-transplant.
Measured: Day+1 to Day +120
Secondary outcomes (8)
Chronic GvHD
The diagnosis of chronic GvHD is based on clinical and pathological evaluation by the principal investigator in collaboration with the treating physician.The analysis will be based on the maximum grade of chronic GvHD
Measured: Day +1 to Day +365
Primary graft failure
Incidence of graft failure will be calculated from date of transplant to failure for all subjects who receive a transplant and any prophylactic treatment and from date of completion of prophylactic treatment for all participants that completed treatment
Measured: Day +1 to Day +30
Poor graft function
Incidence of poor graft function will be calculated, from date of transplant to failure for all subjects who receive a transplant and any prophylactic treatment and from date of completion of prophylactic treatment for all participants that completed treatment
Measured: Day +1 to Day +30
Secondary graft failure
Evaluated after engraftment is achieved will be calculated from date of engraftment for all subjects with engraftment
Measured: Day +1
Treatment-related mortality (TRM)
Analyzed based on participants that who received a transplant with any prophylactic treatment and for all subjects who received a transplant and completed prophylactic treatment.
Measured: Day +1 to Day +730
Relapse rate (RR)
Evaluated to day +730 and will be analyzed for all subjects who received a transplant and for all transplanted subjects that completed treatment
Measured: Day +1 to Day +730
GvHD and relapse-free survival (GRFS)
Evaluated to day +730 and considers as successes participants that are without reported GvHD III-IV acute GvHD, chronic GvHD requiring systemic therapy and have not experienced relapse or death after transplant
Measured: Day +1 to Day +730
Overall survival (OS)
Evaluated to day +730 and considers all participants who received a transplant and for all transplanted subjects who completed prophylactic treatment
Measured: Day +1 to Day +730
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2022
- Study start13 Mar 2022
- Primary completionAug 2026 (estimated)
- Study completionAug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 74 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Northwell Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- A. Samer Al-Homsi, MD, MBA, Principal investigator, Northwell Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05289167
- Sponsor's protocol ID
- 21-00797
- Status last verified
- May 2026
- First submitted
- 10 Mar 2022
- Last updated
- 29 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Information only to approved study team
Study at a glance
From the registry record, last updated by the sponsor on 29 May 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 Allogenic Hematopoietic Stem Cell Transplantation (HSCT)
- ClinicalTrials.gov ID
- NCT05289167
- Acronym / sponsor ID
- 21-00797
- Conditions
- Graft-versus-host Disease
- Keywords
- GvHD, post transplant cyclophosphamide, abatacept
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 74 participants (estimated)
- Lead sponsor
- Northwell HealthUniversity, hospital or other
- Study start
- 13 Mar 2022 (actual)
- Primary completion
- Aug 2026 (estimated)
- Study completion
- Aug 2028 (estimated)
- First posted
- 21 Mar 2022 (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.
This is a phase I-II clinical trial. Adult subjects with hematological malignancies undergoing allogeneic HSCT from an HLA matched sibling or ≥7 out of 8 allele level HLA matched unrelated donor are eligible for the study if they meet the criteria defined in our standard operation procedures (SOPs), meet all inclusion criteria, and do not satisfy any exclusion criteria. Subjects will receive a standard of care conditioning regimen. Subjects will receive investigational PTCy, investigational bortezomib and investigational abatacept as GvHD prophylaxis.
Detailed description
The study will have a phase I and phase II potions. The phase I portion will employ a 3+3 dose escalation design to define the maximum tolerated dose (MTD) of abatacept added to PTCy and bortezomib following HSCT. The phase II portion will consist of two single arm, open label, optimal 2-stage Simon design studies conducted in two separate strata for HLA matched and HLA mismatched donor transplants. Adult patients with hematological malignancies undergoing allogeneic HSCT from an HLA matched sibling or ≥7 out of 8 allele level HLA matched unrelated donor are eligible for the study if they meet the standard criteria defined in our institutional standard operation procedures (SOPs), meet all inclusion criteria, and do not satisfy any exclusion criteria. Subjects will receive a standard of care conditioning regimen followed by peripheral blood hematopoietic stem cells. Subjects with unrelated donors will also receive rabbit anti-thymocyte globulin (rATG). Subjects will receive investigational PTCy, investigational bortezomib and investigational abatacept as GvHD prophylaxis. The phase II portion dose of abatacept will be the MTD as determined in the phase I portion of the study. In the phase II portions, subjects will be stratified based on whether they receive a matched sibling or matched unrelated (matched) donor transplant and ≥7 out of 8, allele level matched (mismatched) unrelated donor transplant.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Participants with hematological malignancies | Experimental | Drug: Cyclophosphamide, Drug: Abatacept, Drug: BortezomibParticipants undergoing Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) will receive a combination of cyclophosphamide, known commercially as Cytoxan®, abatacept, known as Orecia® and bortezomib commercially known as Velcade®, to reduce the rate of graft-versus-host disease (GvHD). These medications will be given for GvHD prevention during the transplant process. |
Who may qualify
- Ages
- 14 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- Age ≥14 years
- Karnofsky score ≥70%
- No evidence of progressive bacterial, viral, or fungal infection
- Creatinine clearance >50 mL/min/1.72m2
- ALT and AST <3 x the upper limit of normal
Key exclusion criteria (10 listed)
- Pregnant or nursing females or women of reproductive capability who are unwilling to completely abstain from heterosexual sex or practice 2 effective methods of contraception from start of conditioning through 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 months in a row.
- 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 New York Heart Association (NYHA) Class III or IV heart failure (see Appendix D), 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.
- Known allergies to any of the components of the investigational treatment regimen.
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 |
|---|---|---|
| CyclophosphamideAlso: Cytoxan®37.5 mg/kg IV over 1 hour on Day +3 and +4 | Drug | Participants with hematological malignancies |
| AbataceptAlso: Orecia®Dose level 0: 10 mg/kg IV over 30-60 minutes on day +5 Dose level 1: 10mg/kg IV over 30-60 minutes on day +5 and +14 Dose level 2: 10mg/kg IV over 30-60 minutes on day +5, +14, and +28 | Drug | Participants with hematological malignancies |
| BortezomibAlso: Velcade®1.3 mg/m2 IV 6 hours after graft infusion completion and 72 hours thereafter. | Drug | Participants with hematological malignancies |
Primary outcome
Phase I:Incidence Dose limiting toxicity (DLT)
Time frame: Day+1 to Day +120
Defined as grade 4 non-hematologic toxicity affecting the oral cavity, gastrointestinal tract, lung, heart, liver, kidney, bladder, or central nervous system.
Phase II: Grades II-IV Acute GvHD
Time frame: Day+1 to Day +120
The first day of grades II-IV acute GvHD will be recorded for that grade. This end point will be evaluated through day +120 post-transplant.
8 secondary outcomes
Chronic GvHD
Time frame: Day +1 to Day +365
Primary graft failure
Time frame: Day +1 to Day +30
Poor graft function
Time frame: Day +1 to Day +30
Secondary graft failure
Time frame: Day +1
Treatment-related mortality (TRM)
Time frame: Day +1 to Day +730
Relapse rate (RR)
Time frame: Day +1 to Day +730
GvHD and relapse-free survival (GRFS)
Time frame: Day +1 to Day +730
Overall survival (OS)
Time frame: Day +1 to Day +730
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 29 May 2026.
- Individual participant dataSharing planned: No. Information only to approved study team
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Graft vs Host Disease
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.
A. Samer Al-Homsi, MD, MBA principal investigator
Northwell Health
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 Cyclophosphamide, Abatacept and Bortezomib in people with 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 12 inclusion and 10 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 29 May 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 (516-734-8973, 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:Incidence Dose limiting toxicity (DLT) (time frame: Day+1 to Day +120). 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 29 May 2026.