RecruitingPhase 1

Genetically Engineered Cells (CD83 CAR T Cells) for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia

CD83 CAR T in Relapsed or Refractory Acute Myeloid Leukemia (AML): A Phase I Trial

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years and older
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Time periods mentioned: 2 months
  • Procedures mentioned: Infusions, Blood draws, CT scans, X-rays, Spinal tap (lumbar puncture)

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "To evaluate the safety and determine the maximal tolerated dose (MTD) of autologous anti-CD83 CAR T-cells (CD83 CAR T cells) administered as a single infusion to refractory/relapsed acute myeloid leukemia (AML) patients."
  • "To evaluate progression-free and overall survival after CAR T cell infusion."
  • "To evaluate the time to hematological recovery after CAR T cell infusion."
  • "To evaluate acute GVHD within 6 weeks after infusion of CAR T cells in patients who relapsed after allogeneic hematopoietic cell transplantation (HCT)."
  • "To evaluate the relationship between baseline levels of CD83 expression on AML blasts and response following CAR T cell infusion."
  • "To evaluate immunity after CAR T cell infusion."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests the safety, side effects, and best dose of CD83 CAR T cells, immune cells changed in a lab to target leukemia cells. It is for adults with acute myeloid leukemia (AML), a blood cancer, that has come back or has not responded to treatment.

This phase I trial tests the safety, side effects, and best dose of genetically engineered cells (CD83 chimeric antigen receptor \[CAR\] T cells) in treating patients with acute myeloid leukemia (AML) that has come back after a period of improvement (relapsed) or has not responded to previous treatment (refractory). CD83 is a protein that is found on AML blasts. Blasts are abnormal immature white blood cells that can multiply uncontrollably: filling up the bone marrow and preventing the production of other cells important for survival. CD83 CAR T cells represent a new cell therapy to eliminate AML blasts, while avoiding the risk for graft versus host disease (GVHD) after stem cell transplant to replace bone marrow or, tumor toxicity like myeloid aplasia where the body's own immune system causes damage to the bone marrow stem cells. Therefore, human CD83 CAR T cells are a promising cell-based approach to preventing two critical complications of stem-cell transplant - GVHD and relapse. Giving CD83 CAR T cells may be safe, tolerable, and/or effective in treating patients with relapsed or refractory AML.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • You must be age 18 or older and have AML that has come back or has not responded to treatment.
  • You must be able to care for yourself, though you may not be able to do normal activities or work. Your doctor must expect you to live at least 12 weeks.
  • Your kidney, liver, heart, and breathing tests must meet study limits. You must not need extra oxygen or have heart failure symptoms or an uncontrolled heartbeat problem.
  • Your blood cell counts must meet study limits. Blood transfusions may help you meet the red blood cell and platelet limits before cell collection.
  • If you had a donor stem cell transplant, it must have been at least 3 months ago. You must stop medicines that weaken the immune system at least 2 weeks before cell collection and have no graft-versus-host disease (GVHD) needing treatment. GVHD happens when donor cells attack your body.
  • You must be considered a possible candidate for a donor stem cell transplant, with possible donors found through a transplant review at Roswell Park Comprehensive Cancer Center.
  • If you can become pregnant, you must have a negative pregnancy blood test and agree to use birth control before joining and for 12 months after participation. Report any possible pregnancy right away.
  • You must understand that the treatment is experimental and sign a consent form before any study procedures.

Who can't join

  • You cannot join if you have acute promyelocytic leukemia, a type of AML, or active leukemia in the brain or spinal cord. Past leukemia there is allowed if it has fully responded to treatment.
  • Certain recent experimental treatments or medicines used to control leukemia cell counts may keep you from joining. The study team must check the medicines and when you received them.
  • Steroid doses greater than 10 mg of prednisone daily, or an equal dose of another steroid, are not allowed at cell collection or within 4 weeks of the CAR T-cell infusion, unless used for GVHD.
  • You cannot join with an ongoing, uncontrolled serious infection, lung disease, or mental health or social concerns. HIV or active hepatitis B or C within 4 weeks of joining also rules you out.
  • You cannot join with another active cancer within the past 2 years, except basal cell skin cancer, cervical cancer treated with surgery meant to cure it, or prostate cancer that has not spread and is being watched.
  • You cannot join if you have active grade II–IV acute GVHD needing treatment, a past solid organ transplant, or an active disease in which your immune system attacks your body that needs immune-weakening medicine.
  • You cannot join if you are pregnant or breastfeeding.
  • You cannot join if you cannot or will not follow study rules, or if the study doctor believes another condition makes this treatment unsuitable for you.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

Inclusion Criteria: * Age ≥ 18 years old. * Karnofsky performance status score ≥ 70%. * Relapsed or refractory AML based upon ELN 2022 criteria. * Creatinine clearance: ≥ 40 mL/min (Cockroft-Gault). * Total bilirubin: ≤ 2mg/dL except for patients with Gilbert's syndrome, hemolysis, or related to disease. * Aspartate aminotransferase (AST) and alanine transaminase (ALT) \< 3.0 x upper limit of normal (ULN). * Left ventricular (LV) ejection fraction: \> 45% and be free of symptomatic congestive heart failure or uncontrolled arrhythmia. * Oxygen (O2) saturation: ≥ 92% on room air without needs for supplemental O2. * Absolute lymphocyte count: ≥ 0.2 x 10\^9/L, HCT of ≥ 27% and platelets of ≥ 20 x 10\^9/L. Transfusion support is allowed to meet HCT and platelet parameters prior to apheresis. * Life expectancy ≥12 weeks from the time of enrollment, per clinical judgment. * Negative serum pregnancy test in females of child-bearing potential (FOCBP). FOCBP is defined as any female who has experienced menarche and who has not undergone successful surgical sterilization or who is not postmenopausal. * If history of allogeneic HCT, must have completed transplant at least 3 months prior, be off immunosuppression, including ruxolitinib, at least 2 weeks prior to apheresis, and have no evidence of GVHD requiring treatment at enrollment. * Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and for 12 months following duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. * Participants must be considered preliminarily eligible for an allogeneic hematopoietic cell transplantation, with potential donors identified per a transplant and cellular therapy consult at Roswell Park Comprehensive Cancer Center. * Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure. Exclusion Criteria: * Concomitant systemic glucocorticoid use at a dose equivalent to \> 10 mg daily prednisone at the time of apheresis and/or within 4 weeks of CD83 CAR T infusion for any reasons other than GVHD. * Diagnosis of acute promyelocytic leukemia (APL; AML M3 by French-American-British \[FAB\] classification). * Active central nervous system (CNS) leukemia; patients with history of CNS leukemia in complete response (CR) are eligible. * Patients enrolled in another investigational therapy protocol for their disease within 14 days or 5 half-lives prior to leukapheresis, whichever is shorter. * Patients requiring agents or any treatments other than hydroxyurea, single agent cytarbine,hypomethylating agents with or without ventoclax and/or targeted agents (i.e., FLT3, IDH2 or IDH1 inhibitors) to control blast counts within 14 days or 5 half-lives (whichever is shorter) prior to lymphodepletion. * Ongoing uncontrolled serious infection, pulmonary disease or psycho/social concerns. * HIV seropositivity or active hepatitis B or C infection within (defined by positive polymerase chain reaction \[PCR\]) 4 weeks of enrollment. * Other active malignancy within 2 years of study entry, except for basal cell cancer of skin, cervical cancer treated surgically with curative intent or localized prostate cancer managed with observational approach. * Active grade II-IV acute GVHD in patients with relapsed AML after HCT requiring treatment. * Prior solid organ transplant. * Active autoimmune disease requiring immunosuppressive therapy. * Pregnant or nursing female participants. * Unwilling or unable to follow protocol requirements. * Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug.

Study sites (1)

NY