Myeloablative Conditioning Orca-T & Allogeneic Donor-Derived CD19/CD22-CAR TCells in B-Cell ALL

NCT05507827 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: IRB-64357NCI-2022-07232
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

To assess the safety of administering allogenic, donor-derived CD19/CD22-CAR T cells that meet established release specifications in adults with B-cell ALL following a myeloablative conditioning regimen and Orca-T to determine if this will augment graft versus leukemia without increasing acute GVHD or graft failure.

Conditions

Lymphoid Leukemia

Outcome Measures

Primary Outcomes (2)

• Number of patients who received donor CD19/CD22-CAR T cells

  Will be measured by the ability to manufacture donor CD19/CD22-CAR T cells that meet established release specifications

  42 days

• Assessment of the donors safety CD19/CD22-CAR T cells plus the Orca-T graft

  Safety of the donor CD19/CD22-CAR T cells plus the Orca-T graft will be assessed by the incidence of engraftment without Grade III to IV acute GVHD

  42 days

Secondary Outcomes (5)

• Cumulative incidence of disease progression

  1 year

• Frequency of secondary graft failure

  1 year

• Progression-free survival

  1 year

• Overall survival

  1 year

• Infectious disease complication

  1 year

Study Arms (1)

Dose escalation

EXPERIMENTAL

Bayesian dose escalation design for the dosing of the donor CD19/CD22-CAR T cells

Drug: Allogeneic donor-derived T-cells transduced with bivalent lentiviral vector (CD19/CD22-BBz) chimeric antigen receptor (CAR); Drug: Treg CD34+HSPC (Orca-T)

Interventions

Allogeneic donor-derived T-cells transduced with bivalent lentiviral vector (CD19/CD22-BBz) chimeric antigen receptor (CAR) DRUG

CD19/C22CAR T cells will be administered at a dose of CAR+ cells/kg body weight via IV administration

Dose escalation

Treg CD34+HSPC (Orca-T) DRUG

Purified donor-derived regulatory T-cell (Treg) plus CD34 + hematopoietic progenitor cells

Dose escalation

Eligibility Criteria

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

You may qualify if:

• Subjects in CR must have a history of chemotherapy refractory disease defined as progression or stable disease after one line of chemotherapy, or relapsed disease after achieving prior CR OR must have other high risk ALL features including: CRLF2 rearrangement, Ph-like phenotype, MLL/KMT2a rearrangement, or hypodiploid karyotype.
• Subjects with persistent or relapsed minimal residual disease (MRD) (by flow cytometry, PCR, FISH, or next generation sequencing) require verification of MRD in the peripheral blood or bone marrow on two occasions at least 2 weeks apart.
• Subjects with active ALL (defined as \>=5% bone marrow blasts, circulating blasts, or extramedullary disease) are eligible.
• Age ≥ 18 and ≤ 65 years (i.e., from age 18 to \< 66 years old) at the time of enrollment
• Eastern cooperative oncology group (ECOG) performance status of 0, 1, or 2; or Karnofsky ≥ 60%
• CD19 expression is required any time since diagnosis. CD19 expression may be detected by immunohistochemistry or by flow cytometry. The choice of whether to use flow cytometry or immunohistochemistry will be determined by what is the most easily available tissue sample in each subject. In general, immunohistochemistry will be used for lymph node biopsies, flow cytometry will be used for peripheral blood and bone marrow samples. Patients receiving prior CD19 CAR T cell or blinatumomab are eligible if there is no documented history of CD19 negativity on the malignant cells.
• Subjects must have an HLA matched related donor willing to undergo unstimulated apheresis for T cell collection for CAR T cell generation followed by GCSF mobilized apheresis for HSC/Treg graft.
• Matched related donor who is an 8/8 match for HLA-A, -B, -C, and -DRB1, all typed using DNA-based high-resolution methods
• Subjects must have adequate organ function measured by:
• Cardiac: Cardiac ejection fraction at rest ≥ 45%
• Hepatic:
• Total bilirubin \< 2 times upper limit of normal (ULN) (patients with Gilbert's syndrome may be included where hemolysis has been excluded and with approval of the study PI)
• ALT/AST \<= 3 times ULN
• Renal: Calculated creatinine clearance ≥ 50 mL/min or serum creatinine \< 2.0 mg/dL
• Pulmonary: Diffusing capacity of the lung for carbon monoxide (DLCO) (adjusted for hemoglobin) ≥ 50%

You may not qualify if:

• History of other malignancy unless disease free for at least 3 years. At the discretion of the Principal Investigator, subjects in remission for 1-2 years prior to enrollment may be deemed eligible after considering the nature of other malignancy, likelihood of recurrence for one year following therapy, and impact of prior treatment on risk of CD19/CD22-CAR T cells and Treg graft. Subjects in remission \<1 year are not eligible. The following exceptions apply:
• Nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) is eligible.
• Hormonal therapy in subjects in remission \>1 year will be allowed.
• Patients who have undergone a prior allogeneic or autologous stem cell transplant.
• Recipient positive anti-donor HLA antibodies against a mismatched allele in the selected donor determined by either:
• a positive crossmatch test of any titer (by complement-dependent cytotoxicity or flow cytometric testing), or
• the presence of anti-donor HLA antibody to any of the following HLA loci: HLA-A, -B, -C, -DRB1, -DQB1, -DQA1, -DPB1, or -DPA1, with mean fluorescence intensity (MFI) \>1000 by solid phase immunoassay
• Presence of fungal, bacterial, viral, or other infection that is uncontrolled. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.
• Known history of infection with any of the following:
• HIV
• Hepatitis B (HBsAg positive) \*\*
• Hepatitis C virus (anti HCV positive) \*\*
• \*\* A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative PCR and/or nucleic acid testing.
• Currently receiving corticosteroids or other immunosuppressive therapy. Topical corticosteroids or oral systemic corticosteroid doses less than or equal to 10 mg/day are allowed.
• Planned pharmaceutical in vivo or ex vivo T cell depletion, e.g., post-transplant cyclophosphamide (Cy), peri-transplant anti-thymocyte globulin (ATG), or alemtuzumab. For patients that have previously been exposed to a T cell-depleting agent, a 5-half-life washout of the agent must occur prior to planned Transplant Day 0.

Sponsors & Collaborators

• Stanford University: lead
• National Marrow Donor Program: collaborator
• American Society of Hematology: collaborator

Study Sites (1)

Stanford Cancer Center

Palo Alto, California, 94305, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphoid

Interventions

Receptors, Chimeric Antigen

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Receptors, Artificial; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Antigen, T-Cell; Receptors, Antigen; Receptors, Immunologic; Receptors, Cytoplasmic and Nuclear

Study Officials

• Lori Muffly, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 17, 2022
• First Posted: August 19, 2022
• Study Start: August 18, 2022
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: September 16, 2025

Record last verified: 2025-09

Locations

US (1)