Trial Title:
Dose Escalation/Dose Expansion Study of PRGN-3007 UltraCAR-T Cells in Patients With Advanced Hematologic and Solid Tumor Malignancies
NCT ID:
NCT05694364
Condition:
Chronic Lymphocytic Leukemia
Mantle Cell Lymphoma
Acute Lymphoblastic Leukemia
Diffuse Large B Cell Lymphoma
Triple Negative Breast Cancer Malignancies
Conditions: Official terms:
Lymphoma
Leukemia
Neoplasms
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Triple Negative Breast Neoplasms
Cyclophosphamide
Fludarabine
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Fludarabine
Description:
Fludarabine is an antimetabolite given prior to lymphodepletion.
Arm group label:
Phase 1 Dose Escalation (Group A)
Arm group label:
Phase 1b Dose Expansion (Group A)
Other name:
Fludara
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
Cyclophosphamide is a nitrogen mustard-derivative, polyfunctional alkylating agent given
prior to lymphodepletion.
Arm group label:
Phase 1 Dose Escalation (Group A)
Arm group label:
Phase 1 Dose Escalation (Group B)
Arm group label:
Phase 1b Dose Expansion (Group A)
Arm group label:
Phase 1b Dose Expansion (Group B)
Intervention type:
Biological
Intervention name:
PRGN-3007
Description:
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.
Arm group label:
Phase 1 Dose Escalation (Group A)
Arm group label:
Phase 1 Dose Escalation (Group B)
Arm group label:
Phase 1b Dose Expansion (Group A)
Arm group label:
Phase 1b Dose Expansion (Group B)
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.
Criteria for eligibility:
Criteria:
Key Inclusion Criteria:
- 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).
Exclusion Criteria:
- 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.
- History of any central nervous system (CNS) disorder such as seizure disorder,
cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, any autoimmune
disease with CNS involvement, posterior reversible encephalopathy syndrome, or
cerebral edema
- History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months
prior to enrollment
- CNS lymphoma, untreated CNS metastases, leptomeningeal disease and/or carcinomatous
meningitis; patients with a history of brain metastases that are previously treated,
stable, and off systemic steroids for over 30 days prior to screening are eligible
- Patients that have not recovered from major acute infections and/or recent surgical
procedures
- Toxicities due to prior therapy must be stable and recovered to ≤ grade 1 (except
for clinically non-significant toxicities such as alopecia)
- Patients, who in the opinion of the investigator, may not be able to comply with the
monitoring requirements of the study
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Moffitt Cancer Center
Address:
City:
Tampa
Zip:
33612
Country:
United States
Status:
Recruiting
Contact:
Last name:
Ashley O'Neil
Phone:
813-745-5240
Email:
ashley.oneil@moffitt.org
Investigator:
Last name:
Javier Pinilla-Ibarz, MD, PhD
Email:
Principal Investigator
Investigator:
Last name:
Julio Chavez, MD, MS
Email:
Sub-Investigator
Investigator:
Last name:
Bijal Shah, MD, MS
Email:
Sub-Investigator
Investigator:
Last name:
Hatem Soliman, MD
Email:
Sub-Investigator
Start date:
January 25, 2023
Completion date:
January 2026
Lead sponsor:
Agency:
H. Lee Moffitt Cancer Center and Research Institute
Agency class:
Other
Collaborator:
Agency:
Precigen, Inc
Agency class:
Industry
Source:
H. Lee Moffitt Cancer Center and Research Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05694364
https://www.moffitt.org/clinical-trials-research/clinical-trials/
