GVHDPhase 2NCT03680092
Comparing Cyclophosphamide and Abatacept With Standard of Care Treatment Following Stem Cell Transplantation
A Phase 2 study testing Cyclophosphamide, abatacept and Methotrexate in people with GVHD and Hematologic Neoplasms, run by Dimitrios Tzachanis, MD PhD at 1 site in United States.
Trial summary
The purpose of this study is to investigate whether the combination of cyclophosphamide and abatacept versus the treatment used in standard of care will reduce the incidence of moderate and severe chronic graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- GVHD, Hematologic Neoplasms
- What is being tested?
- Cyclophosphamide, abatacept and Methotrexate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Nov 2019to 15 Jun 2023
- 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
- High risk hematologic malignancy justifying the need for an allogeneic hematopoetic stem cell transplantation: AML, ALL, CML in accelerated or blast phase, MDS/MPN, NHL, Hodgkin lymphoma, and multiple myeloma
- Creatinine clearance > 40
- Adequate hepatic function
- Normal cardiac function (EF > 50%)
Who cannot join
- Patients with hematologic malignancies for which transplant is not the only curative option, such as AML with good or intermediate cytogenetics or molecular markers in CR1 or CML in chronic phase
- Inability to identify an 10/10 HLA-Matched Donor (related or unrelated) or a haploidentical donor
- Active malignant disease relapse
- Active, uncontrolled infection, uncontrolled cardiac angina, symptomatic congestive heart failure
- Life expectancy <3 months
- Pregnancy or lactation
- Patients may not be receiving any other investigational agents in the last 28 days
- Patients with chronic myeloid leukemia in first chronic phase
Trial locations and contacts
1 site in 1 country.
United States1 site
UC San Diego Moores Cancer Center
La Jolla, California, 92093
About this study
Official title: A Randomized Phase II Trial Comparing a Calcineurin Inhibitor-free Graft-versus-host Disease Prophylaxis Regimen With Post-transplantation Cyclophosphamide and Abatacept to Standard of Care
The purpose of this study is to investigate whether the combination of cyclophosphamide and abatacept versus the treatment used in standard of care will reduce the incidence of moderate and severe chronic graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation. GVHD occurs when the cells from your donor (the graft) see your body's cells (the host) as different and attack them.
Read the detailed description
The experimental GVHD prophylaxis arm consists of cyclophosphamide and abatacept. Cyclophosphamide induces apoptosis of activated T cells and abatacept (CTLA4Ig) blocks activation of T cells by inhibiting the co-stimulatory signal.
Compared to the standard-of-care control arm, the experimental arm is much more convenient and expected to be associated with fewer toxicities.
In addition there is a great theoretical potential for immunological synergy between cyclophosphamide and abatacept for inducing post-transplant immunologic tolerance that clinically might translate into less GVHD without increase in relapse Patients will be randomized 1:1 to the experimental vs the standard of care arm. Randomization will be done prior to the use of any conditional therapy.
The two arms will be stratified by disease (acute leukemia vs others) and donor type (MRD vs MUD/MUD vs Haplo) in an effort to keep them balanced.
The conditioning regimen for both arms will be mainly Busulfan/Fludarabine (A Total Body Irradiation based conditioning regimen will be allowed for diseases such as ALL)
The GVHD prophylaxis regimen on the experimental arm will consist of high dose Cyclophosphamide on Days +3 and +4 followed by abatacept for 6 months.
The GVHD prophylaxis regimen on the standard of care arm will consist of methotrexate on Days +1,+3, +6 and +11 and tacrolimus for patients with a 10/10 matched related or unrelated donor and of high dose cyclophosphamide on Days +3 and +4 followed by tacrolimus and mycophenolate for patients with a haploidentical donor.
- Conditions
- GVHD, Hematologic Neoplasms
- Being tested
- Cyclophosphamide, abatacept, Methotrexate, Tacrolimus
- Keywords
- cancer, Graft-Versus-Host Disease, Hematologic Neoplasms, Abatacept, Cyclophosphamide, GVHD prophylaxis, stem cell transplantation, High risk hematologic malignancy, hematologic malignancy, Allogeneic Hematopoetic Stem Cell Transplantation, GVHD
- Medical subject headings
- Hematologic Neoplasms, Neoplasms, 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 cytophosphane, Cytoxan, Neosar
Day 3 and day 4 following transplant. Dosing will be based on patients' actual weight up to 120% of ideal body weight, above which it will be based on adjusted ideal body weight (ideal weight plus 50% of the difference between ideal and actual weight).
abataceptDrug
Also called ORENCIA
Abatacept at a dose of 10mg/kg will be administered on days +5, +14 and +28, +56, +84, +112, +140, +168
MethotrexateDrug
Also called Trexall
standard of care Methotrexate 5 mg/m2 on Days 1, 3, 6 and 11
TacrolimusDrug
Also called Prograf, Astagraf XL, Envarsus XR
Tacrolimus per institutional guidelines
| Study group | Role | What they receive |
|---|---|---|
| Cyclophosphamide and abatacept | Experimental | The GVHD prophylaxis regimen on the experimental arm will consist of high dose Cyclophosphamide on Days +3 and +4 followed by abatacept for 6 months. Abatacept at a dose of 10mg/kg will be administered on days +5, +14 and +28, +56, +84, +112, +140, +168 Receives: Drug: Cyclophosphamide; Drug: abatacept |
| methotrexate and tacrolimus | Active comparator | The GVHD prophylaxis regimen on the standard of care arm will consist of methotrexate on Days +1,+3, +6 and +11 and tacrolimus Receives: Drug: Methotrexate; Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of Moderate and Severe Chronic GVHD at One Year Post Transplant
The occurrence of moderate and severe chronic GVHD at one year post Chronic GVHD will be diagnosed and staged according to the previously published and widely accepted National Institutes of Health consensus criteria
Measured: through study completion, an average of 1 year
Secondary outcomes (1)
GVHD- and Relapse- Free Survival by One Year Post Transplant
GVHD- and relapse- free survival will be defined as the absence of acute GVHD Grade III or IV or moderate or severe chronic GVHD or relapse or non-relapse mortality by one year post transplant. Acute GVHD will be diagnosed and graded according to Glucksberg criteria
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2018
- Study start26 Nov 2019
- Primary completion15 Jun 2023
- Study completion15 Jun 2023
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for GVHDStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dimitrios Tzachanis, MD PhD
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor-investigator, Dimitrios Tzachanis, MD PhD, University of California, San Diego
- Investigators
- Dimitrios Tzachanis, MD PhD, Principal investigator, University of California, San DiegoDivya Koura, MD, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03680092
- Sponsor's protocol ID
- 180383
- Status last verified
- Sep 2025
- First submitted
- 19 Sep 2018
- Last updated
- 2 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Koura D, Dykes K, Goodman A, Costello C, Mulroney C, Mangan JK, Tanaka TN, Ball ED, Hamdan A, Jeong AR, Mirocha J, Zhang Q, Ogrodnik P, McConnell K, Maroge JJ, Padilla M, Morris GP, Tzachanis D. A prospective clinical trial of GVHD prophylaxis with posttransplant cyclophosphamide and abatacept. Blood Adv. 2025 Aug 26;9(16):4336-4344. doi: 10.1182/bloodadvances.2024015094.
PubMed 40554429
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II Trial Comparing a Calcineurin Inhibitor-free Graft-versus-host Disease Prophylaxis Regimen With Post-transplantation Cyclophosphamide and Abatacept to Standard of Care
- ClinicalTrials.gov ID
- NCT03680092
- Acronym / sponsor ID
- 180383
- Conditions
- GVHD, Hematologic Neoplasms
- Keywords
- cancer, Graft-Versus-Host Disease, Hematologic Neoplasms, Abatacept, Cyclophosphamide, GVHD prophylaxis, stem cell transplantation, High risk hematologic malignancy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Dimitrios Tzachanis, MD PhDUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 26 Nov 2019 (actual)
- Primary completion
- 15 Jun 2023 (actual)
- Study completion
- 15 Jun 2023 (actual)
- First posted
- 21 Sep 2018 (actual)
- Results
- Posted 2 Oct 2024
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 investigate whether the combination of cyclophosphamide and abatacept versus the treatment used in standard of care will reduce the incidence of moderate and severe chronic graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation. GVHD occurs when the cells from your donor (the graft) see your body's cells (the host) as different and attack them.
Detailed description
The experimental GVHD prophylaxis arm consists of cyclophosphamide and abatacept. Cyclophosphamide induces apoptosis of activated T cells and abatacept (CTLA4Ig) blocks activation of T cells by inhibiting the co-stimulatory signal.
Compared to the standard-of-care control arm, the experimental arm is much more convenient and expected to be associated with fewer toxicities.
In addition there is a great theoretical potential for immunological synergy between cyclophosphamide and abatacept for inducing post-transplant immunologic tolerance that clinically might translate into less GVHD without increase in relapse Patients will be randomized 1:1 to the experimental vs the standard of care arm. Randomization will be done prior to the use of any conditional therapy.
The two arms will be stratified by disease (acute leukemia vs others) and donor type (MRD vs MUD/MUD vs Haplo) in an effort to keep them balanced.
The conditioning regimen for both arms will be mainly Busulfan/Fludarabine (A Total Body Irradiation based conditioning regimen will be allowed for diseases such as ALL)
The GVHD prophylaxis regimen on the experimental arm will consist of high dose Cyclophosphamide on Days +3 and +4 followed by abatacept for 6 months.
The GVHD prophylaxis regimen on the standard of care arm will consist of methotrexate on Days +1,+3, +6 and +11 and tacrolimus for patients with a 10/10 matched related or unrelated donor and of high dose cyclophosphamide on Days +3 and +4 followed by tacrolimus and mycophenolate for patients with a haploidentical donor.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cyclophosphamide and abatacept | Experimental | Drug: Cyclophosphamide, Drug: abataceptThe GVHD prophylaxis regimen on the experimental arm will consist of high dose Cyclophosphamide on Days +3 and +4 followed by abatacept for 6 months. Abatacept at a dose of 10mg/kg will be administered on days +5, +14 and +28, +56, +84, +112, +140, +168 |
| methotrexate and tacrolimus | Active comparator | Drug: Methotrexate, Drug: TacrolimusThe GVHD prophylaxis regimen on the standard of care arm will consist of methotrexate on Days +1,+3, +6 and +11 and tacrolimus |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- High risk hematologic malignancy justifying the need for an allogeneic hematopoetic stem cell transplantation: AML, ALL, CML in accelerated or blast phase, MDS/MPN, NHL, Hodgkin lymphoma, and multiple myeloma
- Creatinine clearance > 40
- Adequate hepatic function
- Normal cardiac function (EF > 50%)
Key exclusion criteria (8 listed)
- Patients with hematologic malignancies for which transplant is not the only curative option, such as AML with good or intermediate cytogenetics or molecular markers in CR1 or CML in chronic phase
- Inability to identify an 10/10 HLA-Matched Donor (related or unrelated) or a haploidentical donor
- Active malignant disease relapse
- Active, uncontrolled infection, uncontrolled cardiac angina, symptomatic congestive heart failure
- Life expectancy <3 months
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: cytophosphane, Cytoxan, NeosarDay 3 and day 4 following transplant. Dosing will be based on patients' actual weight up to 120% of ideal body weight, above which it will be based on adjusted ideal body weight (ideal weight plus 50% of the difference between ideal and actual weight). | Drug | Cyclophosphamide and abatacept |
| abataceptAlso: ORENCIAAbatacept at a dose of 10mg/kg will be administered on days +5, +14 and +28, +56, +84, +112, +140, +168 | Drug | Cyclophosphamide and abatacept |
| MethotrexateAlso: Trexallstandard of care Methotrexate 5 mg/m2 on Days 1, 3, 6 and 11 | Drug | methotrexate and tacrolimus |
| TacrolimusAlso: Prograf, Astagraf XL, Envarsus XRTacrolimus per institutional guidelines | Drug | methotrexate and tacrolimus |
Primary outcome
Occurrence of Moderate and Severe Chronic GVHD at One Year Post Transplant
Time frame: through study completion, an average of 1 year
The occurrence of moderate and severe chronic GVHD at one year post Chronic GVHD will be diagnosed and staged according to the previously published and widely accepted National Institutes of Health consensus criteria
1 secondary outcome
GVHD- and Relapse- Free Survival by One Year Post Transplant
Time frame: through study completion, an average of 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40554429Koura D, Dykes K, Goodman A, Costello C, Mulroney C, Mangan JK, Tanaka TN, Ball ED, Hamdan A, Jeong AR, Mirocha J, Zhang Q, Ogrodnik P, McConnell K, Maroge JJ, Padilla M, Morris GP, Tzachanis D. A prospective clinical trial of GVHD prophylaxis with posttransplant cyclophosphamide and abatacept. Blood Adv. 2025 Aug 26;9(16):4336-4344. doi: 10.1182/bloodadvances.2024015094.
- 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.
Dimitrios Tzachanis, MD PhD principal investigator
University of California, San Diego
Divya Koura, MD principal investigator
University of California, San Diego
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 Cyclophosphamide, abatacept and Methotrexate in people with GVHD and Hematologic Neoplasms, run by Dimitrios Tzachanis, MD PhD 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 8 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 2 Oct 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 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 2 Oct 2024). 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?
Occurrence of Moderate and Severe Chronic GVHD at One Year Post Transplant (time frame: through study completion, an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03680092, which also lists 1 linked publication.
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 2 Oct 2025.