Allogeneic CMV-Specific CD19-CAR T Cells Plus CMV-MVA Triplex Vaccine After Matched Related Donor Hematopoietic Cell Transplant for the Treatment of Patients With High-Risk Acute Lymphoblastic Leukemia

NCT06735690 | Recruiting Early Phase 1 DMC FDA Drug

• 3 other identifiers: 24431NCI-2024-10005P30CA033572
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This early phase I trial tests the safety and side effects of allogeneic CMV-specific CD19-CAR T cells plus CMV-MVA vaccine and how well it works in treating patients with high-risk acute lymphoblastic leukemia after a matched related donor (allogeneic) hematopoietic stem cell transplant (alloHSCT). Chimeric antigen receptor (CAR) T-cell therapy is a type of treatment in which T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood, in this study, the T cells are cytomegalovirus (CMV) specific. Then the gene for a special receptor that binds to a certain protein, CD19, on the patient's cancer cells is added to the CMV-specific T cells in the laboratory. The special receptor is called a CAR. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Vaccines made from three CMV tumor associated antigens, may help the body build an effective immune response to kill cancer cells. Giving allogeneic CMV-specific CD19-CAR T cells plus CMV-MVA vaccine after matched related alloHSCT may be safe, tolerable, and/or effective in treating patients with high-risk acute lymphoblastic leukemia.

Conditions

Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events (AEs)

  Will be assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. AEs will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.

  Up to 30 days after last dose of study treatment

• Dose-limiting toxicities (DLT)

  Will be graded according to NCI CTCAE v 5.0, and the revised American Society for Transplantation and Cellular Therapy Cytokine Release Syndrome Cytokine Release Syndrome grading system.

  Up to 28 days after T cell infusion

Secondary Outcomes (9)

• Achieving required cell dose and product release requirements

  Up to first segment of the trial (6 weeks)

• Disease status

  At days 0 and 72 and months 5 and 11

• Secondary graft failure

  Up to 15 years

• Cytomegalovirus reactivation requiring antiviral treatment

  Up to 100 days after transplant

• Acute graft versus host disease (GVHD)

  From date of stem cell infusion to documented/biopsy proven acute GVHD onset date, assessed up 100 days

Study Arms (2)

Part 1 (allo CMV-specific CD19-CAR T cells

EXPERIMENTAL

Patients receive HSCT conditioning regimen followed by alloHSCT per standard of care. Starting 28-49 days after alloHSCT, patients receive allo CMV-specific CD19-CAR T cells IV over 10-15 minutes on day 0. Patients undergo ECHO or MUGA, blood and optional CSF sample collection and bone marrow biopsy and aspiration throughout the study. Patient may also undergo chest x-ray and lumbar puncture as needed per PI discretion and PET/CT or CT as clinically indicated throughout the study. Additionally, patients with neurological abnormalities at baseline may undergo MRI of brain throughout the study.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Biological: Anti-CD19-CAR CMV-specific T-lymphocytes; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Procedure: Echocardiography; Procedure: Leukapheresis; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan; Procedure: Positron Emission Tomography; Other: Transplant Conditioning; Procedure: X-Ray Imaging

Part 2 (allo CMV-specific CD19-CAR T cells, CMV-MVA vaccine)

EXPERIMENTAL

Patients receive HSCT conditioning regimen followed by alloHSCT per standard of care. Starting 28-49 days after alloHSCT, patients receive allo CMV-specific CD19-CAR T cells IV over 10-15 minutes on day 0. Patients receive CMV-MVA triplex vaccine IM on day 28 in the absence of DLTs and may receive an additional CMV-MVA triplex vaccine IM on day 56 in the absence of DLTs during the second evaluation period. Patients undergo ECHO or MUGA, blood and optional CSF sample collection and bone marrow biopsy and aspiration throughout the study. Patient may also undergo chest x-ray and lumbar puncture as needed per PI discretion and PET/CT or CT as clinically indicated throughout the study. Additionally, patients with neurological abnormalities at baseline may undergo MRI of brain throughout the study.

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo alloHSCT

Also known as: Allogeneic, Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT, Stem Cell Transplantation, Allogeneic

Part 1 (allo CMV-specific CD19-CAR T cells

Anti-CD19-CAR CMV-specific T-lymphocytes BIOLOGICAL

Given IV

Also known as: Anti-CD19-CAR CMV-specific T-cells, CMV-specific CD19 CAR-T Cells, CMV-specific CD19-CAR T Cells

Part 1 (allo CMV-specific CD19-CAR T cells

Echocardiography PROCEDURE

Undergo ECHO

Also known as: EC

Part 1 (allo CMV-specific CD19-CAR T cells

Biospecimen Collection PROCEDURE

Undergo blood and optional CSF sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Part 1 (allo CMV-specific CD19-CAR T cells

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow biopsy and aspiration

Part 1 (allo CMV-specific CD19-CAR T cells

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy and aspiration

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Part 1 (allo CMV-specific CD19-CAR T cells

Computed Tomography PROCEDURE

Undergo CT or PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Part 1 (allo CMV-specific CD19-CAR T cells

Leukapheresis PROCEDURE

Undergo leukapheresis

Also known as: Leukocyte Adsorptive Apheresis, Leukocytopheresis, Therapeutic Leukopheresis, White Blood Cell Reduction Apheresis

Part 1 (allo CMV-specific CD19-CAR T cells

Lumbar Puncture PROCEDURE

Undergo lumbar puncture

Also known as: LP, Spinal Tap

Part 1 (allo CMV-specific CD19-CAR T cells

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Part 1 (allo CMV-specific CD19-CAR T cells

Multi-peptide CMV-Modified Vaccinia Ankara Vaccine BIOLOGICAL

Given IM

Also known as: CMV-MVA Triplex Vaccine, Multi-antigen CMV-Modified Vaccinia Ankara Vaccine

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Part 1 (allo CMV-specific CD19-CAR T cells

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Part 1 (allo CMV-specific CD19-CAR T cells

Transplant Conditioning OTHER

Given HSCT conditioning regimen

Also known as: conditioning regimen

Part 1 (allo CMV-specific CD19-CAR T cells

X-Ray Imaging PROCEDURE

Undergo chest x-ray

Also known as: Conventional X-Ray, Diagnostic Radiology, Medical Imaging, X-Ray, Plain film radiographs, Radiographic Imaging, Radiographic imaging procedure (procedure), Radiography, RG, Static X-Ray, X-Ray

Part 1 (allo CMV-specific CD19-CAR T cells

Eligibility Criteria

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

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• If unavailable, exceptions may be granted with study PI approval
• Note: For research participants who do not speak English, a short form consent may be used with a City of Hope (COH) certified interpreter/translator to proceed with screening and leukapheresis, while the request for a translated full consent is processed
• Age: ≥ 18 years
• Karnofsky performance status (KPS) ≥ 70
• Participants with high-risk ALL defined as:
• Any complete remission (CR) with minimal residual disease (MRD)+ (by flow cytometry, polymerase chain reaction \[PCR\] or clonoSEQ) at the time of HSCT; or
• Blasts ≥ 5% at the time of transplant; or
• Complete response (CR)2 or higher irrespective of MRD status; or
• Requiring \> 1 regimen to achieve CR1
• Pathology confirmed CD19+ ALL after the last targeted therapy if the patient has active disease or before the last therapy if the patient is in CR
• Note: CD19 positivity must be documented in a pathology report; however, it is not a requirement that the CD19 testing be performed by a COH pathologist
• Planned allogeneic HSCT (myeloablative or reduced intensity conditioning) according to institutional eligibility requirements with an available 8/8 (HLA A, B, C, DR) allele-matched related is allowed per discretion of the principal investigator. for allogeneic HSCT will be unmanipulated mobilized peripheral blood stem cell (PBSC) or bone marrow

You may not qualify if:

• Participants with active autoimmune disease requiring systemic immune suppressive therapy are not allowed
• Any contraindications to standard conditioning transplant regimens per standard of care practices at COH
• Subjects with clinically significant arrhythmia or arrhythmias not stable on medical management within two weeks of screening
• History or prior diagnosis of other immunologic or inflammatory disease affecting the central nervous system (CNS), including uncontrolled seizure disorder, any measurable masses of CNS, or any other active CNS disease. Note: Research participants with a history of CNS disease that has been effectively treated to complete remission (\< 5 white blood cells \[WBC\]/mm\^3 and no blasts in CSF) will be eligible
• Participants should not have any uncontrolled illness including symptomatic congestive heart failure, unstable angina pectoris, poorly controlled pulmonary disease, or psychiatric illness/social situations that would limit compliance with study requirements
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
• History of stroke or intracranial hemorrhage within 3 months prior to screening
• Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia
• Participants with uncontrolled seizures
• Active viral hepatitis
• History of other malignancies, except for malignancy surgically resected (or treated with other modalities) with curative intent, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; non-muscle invasive bladder cancer; malignancy treated with curative intent with no known active disease present for ≥ 2 years
• Clinically significant uncontrolled illness
• Active infection not responding to antibiotics
• Females only: Pregnant or breastfeeding
• Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Stem Cell Transplantation; Specimen Handling; Biopsy; Leukapheresis; Spinal Puncture; Magnetic Resonance Spectroscopy; Transplantation Conditioning; X-Rays; Phantoms, Imaging

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

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Cytapheresis; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Diagnostic Techniques, Neurological; Punctures; Spectrum Analysis; Chemistry Techniques, Analytical; Immunosuppression Therapy; Immunotherapy; Immunomodulation; Immunologic Techniques; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Equipment and Supplies

Study Officials

• Ibrahim Aldoss

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 11, 2024
• First Posted: December 16, 2024
• Study Start: December 30, 2025
• Primary Completion (Estimated): March 7, 2029
• Study Completion (Estimated): March 7, 2029
• Last Updated: April 27, 2026

Record last verified: 2026-04

Locations

US (1)