Acute Myeloid LeukemiaPhase 1NCT03912064
A Phase 1 Trial of CD25/Treg-depleted DLI Plus Ipilimumab for Myeloid Disease Relapse After Matched-HCT
A Phase 1 study testing Ipilimumab and CD25hi Treg depleted DLI in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by Dana-Farber Cancer Institute at 2 sites in United States.
Trial summary
In this research study, our main goal for the ipilimumab portion of the study is to determine the highest dose of ipilimumab that can be given safely in several courses and to determine what side effects are seen in patients with Acute Myeloid Leukemia (AML), Myelodysplastic Syndromes (MDS), Myeloproliferative… 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 Neoplasms
- What is being tested?
- Ipilimumab and CD25hi Treg depleted DLI
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 2 sitesUnited States
- Study dates
- 10 Jul 2019to 31 Dec 2026
- Phase
- Phase 1
- 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
- Histologically or cytologically confirmed relapse of AML, MDS or MPN (CMML or myelofibrosis or MDS/MPN with ≥5% blasts in the marrow).
- Relapse at ≥2 months after any 8/8 or better HLA-matched HCT
- Available original stem cell donor.
- Age ≥18 years. Because no dosing or adverse event data are currently available on the use of Ipilimumab in participants <18 years of age, children are excluded from this study.
- ECOG performance status ≤2 (Karnofsky performance status ≥60, see Appendix A).
- Recipient donor T cell chimerism ≥20% within 4 weeks prior to cell infusion.
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- <50% bone marrow involvement within 4 weeks prior to cell infusion.
- No systemic corticosteroid therapy for GVHD (≤5 mg of prednisone or equivalent doses of other systemic steroids for non-GVHD, non-autoimmune indications for at least 4 weeks prior to cell infusion).
- No other systemic medications/treatments (e.g. ECP) for GVHD for at least 4 weeks prior to cell infusion.
- Ability to understand and willingness to sign written informed consents.
- Adequate organ function as defined below:
- Total bilirubin: ≤1.5 x institutional upper limit of normal (ULN) (except Gilbert's or disease-related hemolysis, then < 3 x ULN)
- AST(SGOT)/ALT(SGPT): ≤3 x institutional ULN
- creatinine clearance: ≤1.5 x institutional ULN
- O2 saturation: ≥90% on room air
- LVEF >40%
- The effects of CD25/Treg-depleted DLI and Ipilimumab on the developing human fetus are unknown. For this reason and because immunomodulatory agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study or within 23 weeks after the last dose of study drug, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for at least 31 weeks after completion of Ipilimumab administration.
- Negative pregnancy test for females of childbearing potential only
Who cannot join
- Extramedullary relapse involving immuno-privileged sites (e.g. CNS, testes, eyes). Other sites of extramedullary relapse (e.g. leukemia cutis, granulocytic sarcoma) are acceptable.
- Participants who have had anti-tumor chemotherapy or other investigational agents within 4 weeks prior to cell infusion (6 weeks for nitrosoureas or mitomycin C), or immunotherapy within 8 weeks prior, or those who have not recovered from adverse events due to agents administered more than 4 weeks prior. Use of hydroxyurea to control counts within 4 weeks prior to cell infusion is permitted.
- Prior history of DLI
- Prior history of treatment with anti-CTLA-4 or anti-PD-1 pathway therapy, or CD137 agonist therapy.
- Prior history of severe (grade 3 or 4) acute GVHD, or ongoing active GVHD requiring systemic treatment.
- Organ transplant (allograft) recipient.
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- History of allergic reactions attributed to compounds of similar chemical or biologic composition to Ipilimumab or other agents used in study.
- Autoimmune disease: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis]) and motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis). Patients with Hashimoto's thyroiditis are eligible to go on study.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because of the unknown teratogenic risk. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued if the mother is treated on this study.
- HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with agents used in this study. In addition, these participants are at increased risk of lethal infections when treated with marrow- suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
- Individuals with active uncontrolled hepatitis B or C are ineligible as they are at high risk of lethal treatment-related hepatotoxicity after HCT.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
In this research study, our main goal for the ipilimumab portion of the study is to determine the highest dose of ipilimumab that can be given safely in several courses and to determine what side effects are seen in patients with Acute Myeloid Leukemia (AML), Myelodysplastic Syndromes (MDS), Myeloproliferative Neoplasms (MPN), Chronic Myelomonocytic Leukemia (CMML), or Myelofibrosis (MF).
Read the detailed description
This research study is a Phase I clinical trial, which tests the safety of an investigational intervention and also tries to define the appropriate dose of the investigational intervention to use for further studies. "Investigational" means that the intervention is being studied.
The U.S. Food and Drug Administration (FDA) has not approved ipilimumab for this specific disease but it has been approved for other uses. This drug has been used in other research studies and is now FDA-approved for the treatment of melanoma. Many people have also received ipilimumab on research studies for possible treatment of prostate cancer, lymphoma, kidney cancer, ovarian cancer and HIV infection. Information from those other research studies suggests that ipilimumab may help to treat the participant's cancer.
Ipilimumab is an antibody that acts against CTLA-4. An antibody is a common type of protein produced by the body that the immune system (a system that defends the body against potentially harmful particles) uses to find and destroy foreign molecules (particles not typically found in the body) such as bacteria and viruses.
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndromes, Myeloproliferative Neoplasms, Chronic Myelomonocytic Leukemia, Myelofibrosis
- Being tested
- Ipilimumab, CD25hi Treg depleted DLI
- Keywords
- Myelofibrosis, Chronic Myelomonocytic Leukemia, Myeloproliferative Neoplasms, Myelodysplastic Syndromes, Acute Myeloid Leukemia
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Myeloproliferative Disorders, Leukemia, Myelomonocytic, Chronic, Primary Myelofibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IpilimumabDrug
Also called Yervoy
Ipilimumab is an antibody that acts against CTLA-4
CD25hi Treg depleted DLIBiological
Donor lymphocyte product
| Study group | Role | What they receive |
|---|---|---|
| CD25/Treg-depleted DLI + Ipilimumab | Experimental | * Ipilimumab is administered intravenously every 12 weeks
* Patients will receive a defined dose of CD25hi Treg depleted DLI intravenously Receives: Drug: Ipilimumab; Biological: CD25hi Treg depleted DLI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) for DLI
The primary objective of this study is to determine the safety (MTD) of CD25/Treg-depleted donor lymphocyte infusion (DLI) plus Ipilimumab in patients with myeloid relapse after matched-HCT. Participants will be evaluated for dose limiting toxicities (DLTs) at day 43. DLTs explained within section 5.4 of the protocol.
Measured: Day 43 (6 weeks)
Maximum Tolerated Dose (MTD) for Ipilimumab
The primary objective of this study is to determine the safety (MTD) of CD25/Treg-depleted donor lymphocyte infusion (DLI) plus Ipilimumab in patients with myeloid relapse after matched-HCT. Participants will be evaluated for dose limiting toxicities (DLTs) at day 43. DLTs explained within section 5.4 of the protocol.
Measured: Day 43 (6 weeks)
Secondary outcomes (7)
Response Rate as Determined by Complete Remission (CR) and CR With Incomplete Count Recovery (CRi)
Complete remission will be evaluated for each disease, along with duration of complete remission. AML morphological complete remission can be found in Appendix E (E.1.1.), and Relapse from CR/CRi is in E.1.3. MDS/MPN complete remission criteria is found in Appendix F (F.1.1), and criteria for relapse is found in F.1.5.
Measured: Day 43 (6 weeks)
Progression Free Survival
Duration of time from start of treatment to time of objective disease progression or death, whichever comes first. AML progressive disease is defined in Appendix E (E.1.7.), and criteria for MDS/MPN is in Appendix F (F.1.4.).
Measured: Day 92 and Week 60
Overall Survival
Duration of time from start of treatment to time of death.
Measured: Day 92 and Week 60
Incidence of Acute GVHD Rates
Incidence of aGVHD will be measured at the below time point, and grading severity of aGVHD will be standardized using the chart and information in Appendix C.
Measured: Day 92
Incidence of Chronic GVHD Rates
Provider will assess study subject for severity of cGVHD per 2014 NIH consensus criteria at day 92.
Measured: Day 92
Severity of Acute GVHD Rates
Severity of aGVHD will be measured at the below time point, and grading severity of aGVHD will be standardized using the chart and information in Appendix C per Harris et al, 2016 "GVHD Target Organ Staging", where 0 is no GVHD and 4 is severe. For the data table below: Grade I-IV reports any incidence of aGVHD, Grade II-IV reports the number of subjects who developed grade II, III, and IV aGVHD and Grade III-IV reports the number of subjects who developed Grade III and IV aGHVD.
Grade 0: No stage 1-4 of any organ. Grade I: Stage 1-2 skin without liver, upper GI, or lower GI involvement. Grade II: Stage 3 rash and/or stage 1 liver and/or stage 1 upper GI and/or stage 1 lower GI.
Grade III: Stage 2-3 liver and/or stage 2-3 lower GI, with stage 0-3 skin and/or stage 0-1 upper GI.
Grade IV: Stage 4 skin, liver, or lower GI involvement, with stage 0-1 upper GI.
Measured: Day 92
Severity of Chronic GVHD Rates
Provider will assess study subject for severity of cGVHD per 2014 NIH consensus criteria at day 92.
Measured: Day 92
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2019
- Study start10 Jul 2019
- Primary completion24 May 2024
- Study completion31 Dec 2026 (estimated)
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 Dana-Farber Cancer InstituteThe 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, John Koreth, MD, Dana-Farber Cancer Institute
- Investigators
- John Koreth, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03912064
- Sponsor's protocol ID
- 19-142
- Other IDs
- 5P01CA229092-05
- Status last verified
- Dec 2025
- First submitted
- 10 Apr 2019
- Last updated
- 5 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Trial of CD25/Treg-depleted DLI Plus Ipilimumab for Myeloid Disease Relapse After Matched-HCT
- ClinicalTrials.gov ID
- NCT03912064
- Acronym / sponsor ID
- 19-142
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndromes, Myeloproliferative Neoplasms, Chronic Myelomonocytic Leukemia, Myelofibrosis
- Keywords
- Myelofibrosis, Chronic Myelomonocytic Leukemia, Myeloproliferative Neoplasms, Myelodysplastic Syndromes, Acute Myeloid Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 10 Jul 2019 (actual)
- Primary completion
- 24 May 2024 (actual)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 11 Apr 2019 (actual)
- Results
- Posted 5 Jan 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this research study, our main goal for the ipilimumab portion of the study is to determine the highest dose of ipilimumab that can be given safely in several courses and to determine what side effects are seen in patients with Acute Myeloid Leukemia (AML), Myelodysplastic Syndromes (MDS), Myeloproliferative Neoplasms (MPN), Chronic Myelomonocytic Leukemia (CMML), or Myelofibrosis (MF).
Detailed description
This research study is a Phase I clinical trial, which tests the safety of an investigational intervention and also tries to define the appropriate dose of the investigational intervention to use for further studies. "Investigational" means that the intervention is being studied.
The U.S. Food and Drug Administration (FDA) has not approved ipilimumab for this specific disease but it has been approved for other uses. This drug has been used in other research studies and is now FDA-approved for the treatment of melanoma. Many people have also received ipilimumab on research studies for possible treatment of prostate cancer, lymphoma, kidney cancer, ovarian cancer and HIV infection. Information from those other research studies suggests that ipilimumab may help to treat the participant's cancer.
Ipilimumab is an antibody that acts against CTLA-4. An antibody is a common type of protein produced by the body that the immune system (a system that defends the body against potentially harmful particles) uses to find and destroy foreign molecules (particles not typically found in the body) such as bacteria and viruses.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CD25/Treg-depleted DLI + Ipilimumab | Experimental | Drug: Ipilimumab, Biological: CD25hi Treg depleted DLI* Ipilimumab is administered intravenously every 12 weeks * Patients will receive a defined dose of CD25hi Treg depleted DLI intravenously |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Histologically or cytologically confirmed relapse of AML, MDS or MPN (CMML or myelofibrosis or MDS/MPN with ≥5% blasts in the marrow).
- Relapse at ≥2 months after any 8/8 or better HLA-matched HCT
- Available original stem cell donor.
- Age ≥18 years. Because no dosing or adverse event data are currently available on the use of Ipilimumab in participants <18 years of age, children are excluded from this study.
- ECOG performance status ≤2 (Karnofsky performance status ≥60, see Appendix A).
Key exclusion criteria (12 listed)
- Extramedullary relapse involving immuno-privileged sites (e.g. CNS, testes, eyes). Other sites of extramedullary relapse (e.g. leukemia cutis, granulocytic sarcoma) are acceptable.
- Participants who have had anti-tumor chemotherapy or other investigational agents within 4 weeks prior to cell infusion (6 weeks for nitrosoureas or mitomycin C), or immunotherapy within 8 weeks prior, or those who have not recovered from adverse events due to agents administered more than 4 weeks prior. Use of hydroxyurea to control counts within 4 weeks prior to cell infusion is permitted.
- Prior history of DLI
- Prior history of treatment with anti-CTLA-4 or anti-PD-1 pathway therapy, or CD137 agonist therapy.
- Prior history of severe (grade 3 or 4) acute GVHD, or ongoing active GVHD requiring systemic treatment.
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 |
|---|---|---|
| IpilimumabAlso: YervoyIpilimumab is an antibody that acts against CTLA-4 | Drug | CD25/Treg-depleted DLI + Ipilimumab |
| CD25hi Treg depleted DLIDonor lymphocyte product | Biological | CD25/Treg-depleted DLI + Ipilimumab |
Primary outcome
Maximum Tolerated Dose (MTD) for DLI
Time frame: Day 43 (6 weeks)
The primary objective of this study is to determine the safety (MTD) of CD25/Treg-depleted donor lymphocyte infusion (DLI) plus Ipilimumab in patients with myeloid relapse after matched-HCT. Participants will be evaluated for dose limiting toxicities (DLTs) at day 43. DLTs explained within section 5.4 of the protocol.
Maximum Tolerated Dose (MTD) for Ipilimumab
Time frame: Day 43 (6 weeks)
The primary objective of this study is to determine the safety (MTD) of CD25/Treg-depleted donor lymphocyte infusion (DLI) plus Ipilimumab in patients with myeloid relapse after matched-HCT. Participants will be evaluated for dose limiting toxicities (DLTs) at day 43. DLTs explained within section 5.4 of the protocol.
7 secondary outcomes
Response Rate as Determined by Complete Remission (CR) and CR With Incomplete Count Recovery (CRi)
Time frame: Day 43 (6 weeks)
Progression Free Survival
Time frame: Day 92 and Week 60
Overall Survival
Time frame: Day 92 and Week 60
Incidence of Acute GVHD Rates
Time frame: Day 92
Incidence of Chronic GVHD Rates
Time frame: Day 92
Severity of Acute GVHD Rates
Time frame: Day 92
Severity of Chronic GVHD Rates
Time frame: Day 92
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research
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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.
John Koreth, MD principal investigator
Dana-Farber Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ipilimumab and CD25hi Treg depleted DLI in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by Dana-Farber Cancer Institute at 2 sites 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 18 inclusion and 12 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: under way, not looking for participants, as of the sponsor's last update on 5 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 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.
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 5 Jan 2026). 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?
Maximum Tolerated Dose (MTD) for DLI (time frame: Day 43 (6 weeks)). 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 5 Jan 2026.