NCT05694364

Brief Summary

The purpose of the study is to find out if an investigational drug called PRGN-3007 UltraCAR-T cells (PRGN-3007 T cells) can help people with ROR1-positive hematologic chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL) and solid tumor triple negative breast cancer (TNBC) malignancies.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
3

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Jan 2023

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 12, 2023

Completed
11 days until next milestone

First Posted

Study publicly available on registry

January 23, 2023

Completed
2 days until next milestone

Study Start

First participant enrolled

January 25, 2023

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 18, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 18, 2024

Completed
Last Updated

February 6, 2026

Status Verified

February 1, 2026

Enrollment Period

1.2 years

First QC Date

January 12, 2023

Last Update Submit

February 4, 2026

Conditions

Chronic Lymphocytic LeukemiaMantle Cell LymphomaAcute Lymphoblastic LeukemiaDiffuse Large B Cell LymphomaTriple Negative Breast Cancer Malignancies

Outcome Measures

Primary Outcomes (2)

  • Maximum Tolerated Dose (MTD) of PRGN-3007 (Group A)

    Maximum Tolerated Dose of of PRGN-3007 in patients with hematologic malignancies.

    Up to 12 months

  • Maximum Tolerated Dose (MTD) of PRGN-3007 (Group B)

    MTD of PRGN-3007 in patients with solid tumors

    Up to 12 months

Secondary Outcomes (2)

  • Overall Response Rate

    at 12 months

  • Disease Control Rate

    at 12 months

Study Arms (4)

Phase 1 Dose Escalation (Group A)

EXPERIMENTAL

Participants from group A (hematologic malignancies) will undergo leukapheresis followed by lymphodepletion and infusion of PRGN-3007. Lymphodepletion will include 3 days of treatment with fludarabine (30 mg/m\^2) and cyclophosphamide (500 mg/m\^2) prior to study day 0. Participants will then receive PRGN-3007 in 3 dose levels beginning at Dose Level 1, using a standard 3+3 escalation design to determine Maximum Tolerated Dose (MTD). The target maximum doses infused at each dose level is: Dose Level 1: 1x10\^6 cells/kg Dose Level 2: 3x10\^6 cells/kg Dose Level 3: 1x10\^7 cells/kg

Drug: FludarabineDrug: CyclophosphamideBiological: PRGN-3007

Phase 1 Dose Escalation (Group B)

EXPERIMENTAL

Participants from group B (solid tumors) will undergo leukapheresis followed by lymphodepletion and infusion of PRGN-3007. Lymphodepletion will include 2 days of cyclophosphamide (500 mg/m\^2) prior to study day 0. Participants will then receive PRGN-3007 in 3 dose levels beginning at Dose Level 1, using a standard 3+3 escalation design to determine Maximum Tolerated Dose (MTD). The target maximum doses infused at each dose level is: Dose Level 1: 1x10\^6 cells/kg Dose Level 2: 3x10\^6 cells/kg Dose Level 3: 1x10\^7 cells/kg

Drug: CyclophosphamideBiological: PRGN-3007

Phase 1b Dose Expansion (Group A)

EXPERIMENTAL

Participants from group A (hematologic malignancies) will undergo leukapheresis followed by lymphodepletion and infusion of PRGN-3007. Lymphodepletion will include 3 days of treatment with fludarabine (30 mg/m\^2) and cyclophosphamide (500 mg/m\^2) prior to study day 0. Participants will then receive PRGN-3007 at the dose level determined to be the Maximum Tolerated Dose (MTD) in the dose escalation portion of the study.

Drug: FludarabineDrug: CyclophosphamideBiological: PRGN-3007

Phase 1b Dose Expansion (Group B)

EXPERIMENTAL

Participants from group B (solid tumors) will undergo leukapheresis followed by lymphodepletion and infusion of PRGN-3007. Lymphodepletion will include 2 days of cyclophosphamide (500 mg/m\^2) prior to study day 0.Participants will then receive PRGN-3007 at the dose level determined to be the Maximum Tolerated Dose (MTD) in the dose escalation portion of the study.

Drug: CyclophosphamideBiological: PRGN-3007

Interventions

FludarabineDRUG

Fludarabine is an antimetabolite given prior to lymphodepletion.

Also known as: Fludara
Phase 1 Dose Escalation (Group A)Phase 1b Dose Expansion (Group A)
CyclophosphamideDRUG

Cyclophosphamide is a nitrogen mustard-derivative, polyfunctional alkylating agent given prior to lymphodepletion.

Phase 1 Dose Escalation (Group A)Phase 1 Dose Escalation (Group B)Phase 1b Dose Expansion (Group A)Phase 1b Dose Expansion (Group B)
PRGN-3007BIOLOGICAL

PRGN-3007 T cells are autologous T cells that are genetically modified ex vivo with the Sleeping Beauty (SB) system to express a ROR1-specific chimeric antigen receptor (ROR1 CAR), membrane bound interleukin-15 (mbIL15), a kill switch derived from truncated form of human epidermal growth factor receptor (HER1t) and include a built-in mechanism for intrinsic downregulation of programmed cell death receptor 1 (PD-1) expression on UltraCAR-T cells.The transgenes are delivered from a SB transposon which ensures co-expression all transgenes in all transfected cells. T cells are selected from the apheresis product and can be modified with the SB system to manufacture the T cells with the potential of infusing within 2 days from genetic modification.

Phase 1 Dose Escalation (Group A)Phase 1 Dose Escalation (Group B)Phase 1b Dose Expansion (Group A)Phase 1b Dose Expansion (Group B)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age 18 years and older
  • Eastern Cooperative Oncology Group (ECOG) score of 0 or 1; or Karnofsky Performance Status (KPS) of ≥ 70%.
  • Life expectancy ≥ 12 weeks from the time of enrollment
  • Must have adequate organ function, as defined in protocol.
  • Patients must be at least 2 weeks or 5 half-lives (whichever is shorter)post systemic steroids prior to enrollment except as premedication for contrast allergy
  • Negative serum pregnancy test for women of child bearing potential (WOCBP). Fertile male and female patients must be willing to use a contraceptive method before, during, and for at least 12 months after the last T cell infusion
  • All patients must have the ability to understand and willingness to sign a written informed consent form (ICF).

You may not qualify if:

  • Patient has received any of the following treatments prior to leukapheresis: cytotoxic chemotherapy or radiation therapy within 14 days; an antineoplastic monoclonal antibody within prior 4 weeks; prior targeted therapy 14 days or 5 half-lives from the last dose whichever is shorter; or prior systemic inhibitory/stimulatory immune checkpoint molecule therapy (eg, ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists) within 3 half-lives; or has not recovered from (i.e., ≤ grade 1) adverse event (AE) caused by prior treatment. Exceptions include hydroxyurea, single agent vincristine or steroids for uncontrolled ALL.
  • Burkitt lymphoma is excluded.
  • Prior allogeneic hematopoietic stem cell transplant (HSCT) or donor lymphocyte infusion within 6 months prior to enrollment, current acute graft versus host disease grade 2-4 by Glucksberg criteria or severity B-D by by International Bone Marrow Transplant Registry (IBMTR) index or history of severe (grade 3-4) acute graft versus host disease.
  • Patients with a history of immunodeficiency (except for acquired hypogammaglobulinemia), patients with active autoimmune disease requiring systemic immunosuppressive therapy (i.e., \> 15 mg of prednisone daily or equivalent), or patients who have received any other form of immunosuppressive therapy within 7 days prior to leukapheresis.
  • Patients with a history of autoimmune disease resulting in end-organ injury are not eligible unless attributable to primary disease which is target of this study
  • Patient requires treatment with warfarin.
  • Patients who have contraindication to the lymphodepletion chemotherapy regimen
  • Patient received a live vaccine administration within 4 weeks prior to leukapheresis
  • Patient is currently participating in another investigation treatment study, or has participated in a study of an investigational agent within 4 weeks prior to leukapheresis.
  • Patients with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing; those with a forced expiratory volume at one second(FEV1) of ≤ 65% or diffuse capacity lung for carbon monoxide (DLCO; corrected) \< 40% will be excluded
  • Patients with history of other active malignancy within 1 year prior to enrollment.
  • Patients with adequately resected basal or squamous cell carcinoma of the skin, non-melanoma skin cancer or carcinoma in situ (e.g., skin, cervix, bladder, breast), superficial bladder cancer, asymptomatic localized low grade prostate cancer for which watch-and-wait approach is standard of care, or any other cancer that has been in remission are eligible
  • History of concomitant genetic syndrome associated with bone marrow failure such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome
  • Known human immunodeficiency virus (HIV) seropositivity or active hepatitis B or C infection. A history of hepatitis B or C is permitted if the viral load is undetectable by quantitative assay
  • Ongoing uncontrolled serious infection, clinically significant cardiac disease (i.e.,symptomatic congestive heart failure, myocardial infarction, cardiac angioplasty or stenting, unstable angina pectoris, uncontrolled cardiac arrhythmia), poorly controlled pulmonary disease (no clinically significant pleural effusion), or psychiatric illness/social situations that would limit compliance with study requirements within 12 months prior to enrollment.
  • +6 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Related Links

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-CellLymphoma, Mantle-CellPrecursor Cell Lymphoblastic Leukemia-LymphomaLymphoma, Large B-Cell, Diffuse

Interventions

fludarabinefludarabine phosphateCyclophosphamide

Condition Hierarchy (Ancestors)

Leukemia, B-CellLeukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLymphoma, Non-HodgkinLymphomaLymphoma, B-Cell

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus Compounds

Study Officials

  • Javier Pinilla-Ibarz, MD, PhD

    Moffitt Cancer Center

    PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

First Submitted

January 12, 2023

First Posted

January 23, 2023

Study Start

January 25, 2023

Primary Completion

April 18, 2024

Study Completion

April 18, 2024

Last Updated

February 6, 2026

Record last verified: 2026-02

Locations

US(1)