A Phase 1 Trial of CD25/Treg-depleted DLI Plus Ipilimumab for Myeloid Disease Relapse After Matched-HCT

NCT03912064 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 2 other identifiers: 19-1425P01CA229092-05
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

Brief 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 Neoplasms (MPN), Chronic Myelomonocytic Leukemia (CMML), or Myelofibrosis (MF).

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndromes; Myeloproliferative Neoplasms; Chronic Myelomonocytic Leukemia; Myelofibrosis

Keywords

Myelofibrosis; Chronic Myelomonocytic Leukemia; Myeloproliferative Neoplasms; Myelodysplastic Syndromes; Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Day 43 (6 weeks)

Secondary Outcomes (7)

• Response Rate as Determined by Complete Remission (CR) and CR With Incomplete Count Recovery (CRi)

  Day 43 (6 weeks)

• Progression Free Survival

  Day 92 and Week 60

• Overall Survival

  Day 92 and Week 60

• Incidence of Acute GVHD Rates

  Day 92

• Incidence of Chronic GVHD Rates

  Day 92

Study Arms (1)

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

Drug: Ipilimumab; Biological: CD25hi Treg depleted DLI

Interventions

Ipilimumab DRUG

Ipilimumab is an antibody that acts against CTLA-4

Also known as: Yervoy

CD25/Treg-depleted DLI + Ipilimumab

CD25hi Treg depleted DLI BIOLOGICAL

Donor lymphocyte product

CD25/Treg-depleted DLI + Ipilimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• \<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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• Dana-Farber Cancer Institute: lead

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Myeloproliferative Disorders; Leukemia, Myelomonocytic, Chronic; Primary Myelofibrosis

Interventions

Ipilimumab

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: John Koreth, MD, PhD, MBBS
• Organization: Dana-Farber Cancer Institute

John_Koreth@dfci.harvard.edu

617-632-3470

Study Officials

• John Koreth, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 10, 2019
• First Posted: April 11, 2019
• Study Start: July 10, 2019
• Primary Completion: May 24, 2024
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 5, 2026
• Results First Posted: January 5, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication.
• Access Criteria: BCH - Contact the Technology \& Innovation Development Office at www.childrensinnovations.org or email TIDO@childrens.harvard.edu BIDMC - Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu BWH - Contact the Partners Innovations team at http://www.partners.org/innovation DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu MGH - Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (2)