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

NCT05535855 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 22-0054.ccNCI-2023-05480
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

This open-label, single arm Phase 1/1b trial aims to determine the safety and tolerability of anti-CD19 chimeric antigen receptor-expressing (CAR) T cells (UCD19 CAR T) in adults with B-ALL that are in first complete remission with MRD positivity. This trial will enroll 10 patients during Phase 1 for apheresis, treatment with lymphodepleting chemotherapy, and UCD19 CAR T cell infusion. Patients will be assessed for DLTs (within 42 days after CAR T infusion) to determine a maximum tolerated dose (MTD), duration of B cell aplasia, overall response rate (at 1-3-, 6- and 12-months), and overall survival and event free survival (at 12- and 24- months) post UCD19 CAR T infusion. After the initial dose escalation phase, an additional 12 participants will be enrolled in the dose expansion at the MTD to determine preliminary efficacy.

Conditions

Acute Lymphoid Leukemia; Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (3)

• Safety of UCD19 CAR T in Adults With B-ALL in first complete remission with MRD Positivity: occurrence and frequency of Adverse Events (AEs)

  The occurrence and frequency of Adverse Events will be graded using the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grading criteria.

  Up to 30 days after last day of study participation

• Safety of UCD19 CAR T in Adults With B-ALL in first complete remission with MRD Positivity: occurrence of Dose Limiting Toxicities (DLTs)

  Adverse events that are at least possibly related to the UCD19 CAR T cells with onset within the first 42 days following UCD19 CAR T cell infusion and are ≥ Grade 3 in severity will be considered DLTs. With exception to hematological toxicity for subjects with normal, Grade 1 or Grade 2 Hematologic Parameters at baseline (independent of transfusion) and cytopenias NOT due to Bone Marrow Involvement by Disease. However, any Grade 4 hematological toxicity (i.e., neutropenia or thrombocytopenia with the exception of lymphopenia) persisting beyond 42 days after infusion will be considered a DLT unless toxicity is attributed to patient's underlying disease.

  42 days

• Preliminary efficacy of UCD19 CAR T infusion at the MTD in adult B-ALL patients at first complete remission with MRD positivity

  Determine the Relapse Free Survival (RFS) rate post UCD19 CAR T infusion. RFS will be measured from the date of infusion of the UCD19 CAR T product to the time of relapse or death from any cause

  12 and 24 months

Secondary Outcomes (3)

• Overall response rate (ORR) at 1, 3, 6, 12, and 24 months post UCD19 CAR T infusion as measured by MRD.

  1, 3, 6, 12, and 24 months

• Overall Survival (OS) at 12 and 24 months post UCD19 CAR T infusion.

  12 and 24 months

• Event Free Survival (EFS) at 12 and 24 months post UCD19 CAR T infusion

  12 and 24 months

Other Outcomes (2)

• Duration of B-cell aplasia

  12 months

• Assessment of minimal residual disease by next generation sequencing

  1, 3, 6, and 12 months

Study Arms (1)

UCD19 CAR T Infusion

EXPERIMENTAL

Lymphodepleting chemotherapy followed by infusion of UCD19 CAR T cells. Infusion is subject to a seven (7) day delay following chemotherapy completion if needed for resolution of clinical toxicities or to allow for product release.

Drug: CD19 Directed CAR T Cell

Interventions

CD19 Directed CAR T Cell DRUG

The UCD19 CAR T cells are developed through transfection of autologous peripheral blood mononuclear cells with a lentivirus carrying the DNA that encodes a short chain fragment variable region (scFv) derived from an anti-CD19 monoclonal antibody, among other elements.

Also known as: UCD19 CAR T cells

UCD19 CAR T Infusion

Eligibility Criteria

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

You may qualify if:

• Age: ≥ 18 years of age with no upper age limit
• ECOG Performance Status ≤ 2
• Confirmed B-cell ALL in first complete morphologic remission
• MRD positivity as defined by:
• 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 (≥ 3 systemic anti-leukemia chemotherapy agents).
• For Ph+ ALL: \> 0.01% by FACS, \> 0 clonal sequences by NGS (clonoSEQ), or less than complete molecular remission (undetectable BCR-ABL1 transcripts by RT-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.
• Peripheral blood CD3 count must be \> 0.15 x 106 cells/mL within 21 days prior to proceeding with apheresis.
• Adequate organ function as defined by:
• Absolute neutrophil count (ANC) ≥ 500/μL.
• Platelet count ≥ 50,000/μL.
• Renal: Either Creatinine ≤ 2 mg/dL OR creatinine clearance (as estimated by Cockcroft Gault equation) ≥ 60 mL/min.
• Hepatic: Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 2.5 upper limit of normal (ULN).
• Total bilirubin ≤ 1.5 mg/dL, except in subjects with Gilbert's syndrome where a bilirubin \< 3.0 mg/dL will be acceptable.
• Cardiac: Ejection fraction ≥ 45%, no evidence of physiologically significant pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings at the time of screening.
• Pulmonary: No clinically significant pleural effusion.

You may not qualify if:

• Previous CAR T therapy.
• Relapsed or refractory B-cell acute lymphoblastic leukemia, including patients who have evidence of MRD after having previously documented MRD-negative remission.
• Mixed phenotype acute leukemia or Burkitt's lymphoma
• Not in hematological remission at time of enrollment (Remission is defined as \< 5% blasts)
• Signs or symptoms of active CNS disease or detectable evidence of CNS disease on MRI at the time of screening. Subjects who have been previously treated for CNS disease but have no evidence of disease at screening are eligible.
• History of malignancy unless disease free for at least 3 years. Exceptions include non-melanoma skin cancer or carcinoma in situ (e.g., cervix, bladder, breast).
• 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.
• Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (hepatitis B surface antigen \[HBsAg\] positive) or hepatitis C.
• 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.
• Venous thrombosis or embolism not managed on a stable regimen of anticoagulation.
• Any medical condition that in the judgement of the Sponsor is likely to interfere with assessment of safety or efficacy of study treatment.
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• Females planning to become pregnant during the course of the study.
• Lymphodepleting Chemotherapy Eligibility
• Disease restaging studies will be performed as clinically indicated but must be within 14 days prior to initiation of lymphodepletion.

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Hospital

Aurora, Colorado, 80045, United States

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Mathew Angelos, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Derek Schatz

CONTACT

17208480628; derek.schatz@cuanschutz.edu

Mathew Angelos, MD

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2022
• First Posted: September 10, 2022
• Study Start: January 24, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2030
• Last Updated: March 11, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)