UCD19 CAR T Therapy in Adults With B-ALL and MRD Positivity in CR1

Launched by UNIVERSITY OF COLORADO, DENVER · Sep 6, 2022

Keywords

ClinConnect Summary

This clinical trial is investigating a new treatment called UCD19 CAR T therapy for adults with a type of blood cancer known as B-cell acute lymphoblastic leukemia (B-ALL). Specifically, it focuses on patients who have achieved their first complete remission but still have minimal residual disease (MRD), which means there are still some cancer cells present even though the major signs of cancer are gone. The goal of the study is to see how safe and well-tolerated this therapy is for participants. The trial will involve 10 patients who will receive a specific type of chemotherapy followed by the UCD19 CAR T cell infusion. Researchers will monitor the participants closely for side effects and how well the treatment works over the following months.

To be eligible for this trial, participants must be at least 18 years old and have a confirmed diagnosis of B-cell ALL. They should be in their first complete remission but still have detectable MRD. Other important criteria include having stable health conditions and sufficient organ function. Participants will need to commit to long-term follow-up after treatment and give informed consent. Throughout the trial, patients can expect regular check-ups to assess their health and the effectiveness of the therapy, as well as support from the medical team. This trial is an early phase study, meaning researchers are still determining the best way to use this new treatment safely.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Age: ≥ 18 years of age with no upper age limit
• • 2. ECOG Performance Status ≤ 2
• • 3. Confirmed B-cell ALL in first complete morphologic remission
• 4. MRD positivity as defined by:
• • 1. For Ph- ALL: \> 0.01% by FACS or \> 0 clonal sequences by NGS (clonoSEQ). MRD assessment for eligibility must be at least 28 days after the start of SOC induction therapy. Remission-induction therapy must have consisted of multi-agent chemotherapy (\> or =3 systemic anti-leukemia chemotherapy agents).
• • 2. For Ph+ ALL: \> 0.01% by FACS, or \> 0 clonal sequences by NGS (clonoSEQ), or less than complete molecular remission (undetectable BCR-ABL1 transcripts by quantitative PCR assay with sensitivity of at least 1 in 100,000). MRD assessment for eligibility must be at least 57 days after the start of SOC induction therapy. Remission-induction therapy must have consisted of a BCR-ABL1 directed tyrosine kinase inhibitor and at least one other systemic anti-leukemia chemotherapy agent.
• • 5. Peripheral blood CD3 count must be \> 0.15 x 106 cells/mL within 21 days prior to proceeding with apheresis.
• • 6. Toxicities from prior therapy must be stable and recovered to ≤ grade 2 (except for clinically non-significant toxicities such as alopecia).
• 7. Adequate organ function as defined by:
• • 1. Absolute neutrophil count (ANC) ≥ 750/μL.
• • 2. Platelet count ≥ 50,000/μL.
• • 3. Renal: Creatinine ≤ 2 mg/dL OR creatinine clearance (as estimated by Cockcroft Gault equation) ≥ 60 mL/min.
• • 4. Hepatic: Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 2.5 upper limit of normal (ULN).
• • 5. Total bilirubin ≤ 1.5 mg/dL, except in subjects with Gilbert's syndrome where a bilirubin \<3.0 mg/dL will be acceptable.
• • 6. Cardiac: Ejection fraction ≥ 45%, no evidence of physiologically significant pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings.
• • 7. Pulmonary: No clinically significant pleural effusion.
• • i. Baseline oxygen saturation \> 92% on room air and; ii. Pulmonary Function Test: Diffuse capacity of the lungs for carbon monoxide (DLCO), forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) are all ≥50% of predicted by spirometry after correcting for hemoglobin.
• • 8. Females of childbearing potential must have a negative serum pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential).
• • 9. Subjects of childbearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for 12 months after receiving the UCD19 infusion; females of childbearing potential must have a negative pregnancy test.
• • 10. Must be able to give informed consent; subjects unable to give informed consent will not be eligible for this study.
• • 11. Be able to consent to long-term follow-up protocol
• Exclusion Criteria:
• • 1. Previous CAR T therapy.
• • 2. Relapsed or refractory B-cell acute lymphoblastic leukemia, including patients who have evidence of MRD after having previously documented MRD-negative remission.
• • 3. Mixed phenotype acute leukemia or Burkitt's lymphoma
• • 4. Not in hematological remission (\>5% blasts) at time of enrollment
• • 5. Signs or symptoms of active CNS disease or detectable evidence of CNS disease by assessment of cerebrospinal fluid at the time of screening. Subjects with leukemic involvement of the CSF at diagnosis who have no detectable leukemic cells in the CSF at screening are eligible.
• • 6. History of malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g., cervix, bladder, breast) unless disease free for at least 3 years.
• • 7. Uncontrolled fungal, bacterial, viral, or other infection requiring antimicrobials for management; simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.
• • 8. Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (hepatitis B surface antigen \[HBsAg\] positive) or hepatitis C.
• • 9. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment or have cardiac atrial or cardiac ventricular lymphoma involvement.
• • 10. Venous thrombosis or embolism not managed on a stable regimen of anticoagulation.
• • 11. Any medical condition that in the judgement of the sponsor is likely to interfere with assessment of safety or efficacy of study treatment.
• • 12. History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• • 13. Females planning to become pregnant during the course of the study.