Genetically Engineered Cells (CD83 CAR T Cells) for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorRoswell Park Cancer Institute
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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).
Disqualifiers
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.
Trial design
Design model
Single group
Treatments tested in this trial
Autologous Anti-CD83 CAR T-cells
DrugGiven IV
Biospecimen Collection
Procedure/SurgeryUndergo bone marrow aspiration blood sample collection
Chest Radiography
Procedure/SurgeryUndergo chest x-ray
Computed Tomography
Procedure/SurgeryUndergo CT
Cyclophosphamide
DrugGiven IV
Echocardiography
Procedure/SurgeryUndergo ECHO
Fludarabine Phosphate
DrugGiven IV
Hydroxyurea
DrugGiven hydroxyurea
Leukapheresis
Procedure/SurgeryUndergo leukapheresis
Lumbar Puncture
Procedure/SurgeryUndergo lumbar puncture
Positron Emission Tomography
Procedure/SurgeryUndergo PET
Questionnaire Administration
Other interventionAncillary studies
Treatment groups
26 Participants
are divided into 1 treatment groupGroup A: Treatment (fludarabine, cyclophosphamide, CD83 CAR T-cells)Experimental treatment 12 interventions
Trial outcomes
Primary outcomes
1
Incidence of dose-limiting toxicity (DLT)
Will be defined as any adverse events based on Common Terminology Criteria for Adverse Events (CTCAE) version (v)5. Cytokine release syndrome(CRS)/immune effector cell-associated neurotoxicity syndrome will be graded according to American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Guidelines. The DLTs will be summarized by dose level using frequencies and relative frequencies. Will employ the Bayesian optimal interval design to find the maximal tolerated dose (MTD). The target DLT rate for the MTD is = 0.33.
Time frame
Up to 28 daysSecondary outcomes
1
Objective response
Will be determine as the number of patients achieving complete remission, partial remission, and/or morphologic leukemia free state by 2022 European Leukemia Net Response Criteria. Will be summarized by dose level using frequencies and relative frequencies. Rates will be estimated using 95% credible regions obtained by Jeffrey's prior method. As exploratory analyses, comparisons between dose levels may be made using Fisher's exact test.
Time frame
At 28 days and 1 year2
Overall survival
Will be summarized by dose level using cumulative incidence or Kaplan-Meier curves, as appropriate. Estimates of the median times will be obtained with 95% confidence intervals calculated using the log-log transformation. As exploratory analyses, comparisons between dose levels may be made using Gray's or the log-rank test, as appropriate.
Time frame
From treatment initiation until death due to any cause or last follow-up, assessed up to 1 year3
Progression-free survival
Will be summarized by dose level using cumulative incidence or Kaplan-Meier curves, as appropriate. Estimates of the median times will be obtained with 95% confidence intervals calculated using the log-log transformation. As exploratory analyses, comparisons between dose levels may be made using Gray's or the log-rank test, as appropriate.
Time frame
From treatment initiation until disease progression/relapse, death due to any cause, subsequent treatment (censored), or last follow-up, assessed up to 1 year4
Hematologic recovery
Will be assessed by achieving an absolute neutrophil count recovery (\> 0.5 x 10\^9/L). Will be summarized by dose level using frequencies and relative frequencies. Rates will be estimated using 95% credible regions obtained by Jeffrey's prior method. As exploratory analyses, comparisons between dose levels may be made using Fisher's exact test.
Time frame
At 28 daysSponsors and contacts
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Roswell Park Cancer Institute
Lead sponsor
United States Department of Defense
Collaborator
Source ClinicalTrials.gov