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

  • STATUS
    Recruiting
  • End date
    May 31, 2024
  • participants needed
    25
  • sponsor
    Dana-Farber Cancer Institute
Updated on 25 March 2022
graft versus host disease
myeloid leukemia
myelofibrosis
myelodysplastic syndromes
myeloproliferative disorder
chronic myelomonocytic leukemia
corticosteroid therapy
leukemia
bone marrow procedure
blast cells
hemolysis
ipilimumab
myelomonocytic leukemia
myelodysplastic/myeloproliferative neoplasm
myelodysplastic/myeloproliferative neoplasms

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).

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.

Details
Condition Acute Myeloid Leukemia, Myelodysplastic Syndromes, Myeloproliferative Neoplasms, Chronic Myelomonocytic Leukemia, Myelofibrosis
Treatment Ipilimumab, CD25hi Treg depleted DLI
Clinical Study IdentifierNCT03912064
SponsorDana-Farber Cancer Institute
Last Modified on25 March 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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 first 8/8 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
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
Negative pregnancy test for females of childbearing potential only
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

Exclusion Criteria

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
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