Dose Escalation/Dose Expansion Study of PRGN-3007 UltraCAR-T Cells in Patients With Advanced Hematologic and Solid Tumor Malignancies
- Conditions
- Diffuse Large B Cell LymphomaTriple Negative Breast Cancer MalignanciesChronic Lymphocytic LeukemiaMantle Cell LymphomaAcute Lymphoblastic Leukemia
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- Not specified
Key Inclusion Criteria:<br><br> - Age 18 years and older<br><br> - Eastern Cooperative Oncology Group (ECOG) score of 0 or 1; or Karnofsky Performance<br> Status (KPS) of = 70%.<br><br> - Life expectancy = 12 weeks from the time of enrollment<br><br> - Must have adequate organ function, as defined in protocol.<br><br> - Patients must be at least 2 weeks or 5 half-lives (whichever is shorter)post<br> systemic steroids prior to enrollment except as premedication for contrast allergy<br><br> - Negative serum pregnancy test for women of child bearing potential (WOCBP). Fertile<br> male and female patients must be willing to use a contraceptive method before,<br> during, and for at least 12 months after the last T cell infusion<br><br> - All patients must have the ability to understand and willingness to sign a written<br> informed consent form (ICF).<br><br>Exclusion Criteria:<br><br> - Patient has received any of the following treatments prior to leukapheresis:<br> cytotoxic chemotherapy or radiation therapy within 14 days; an antineoplastic<br> monoclonal antibody within prior 4 weeks; prior targeted therapy 14 days or 5<br> half-lives from the last dose whichever is shorter; or prior systemic<br> inhibitory/stimulatory immune checkpoint molecule therapy (eg, ipilimumab,<br> nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists) within 3<br> half-lives; or has not recovered from (i.e., = grade 1) adverse event (AE) caused by<br> prior treatment. Exceptions include hydroxyurea, single agent vincristine or<br> steroids for uncontrolled ALL.<br><br> - Burkitt lymphoma is excluded.<br><br> - Prior allogeneic hematopoietic stem cell transplant (HSCT) or donor lymphocyte<br> infusion within 6 months prior to enrollment, current acute graft versus host<br> disease grade 2-4 by Glucksberg criteria or severity B-D by by International Bone<br> Marrow Transplant Registry (IBMTR) index or history of severe (grade 3-4) acute<br> graft versus host disease.<br><br> - Patients with a history of immunodeficiency (except for acquired<br> hypogammaglobulinemia), patients with active autoimmune disease requiring systemic<br> immunosuppressive therapy (i.e., > 15 mg of prednisone daily or equivalent), or<br> patients who have received any other form of immunosuppressive therapy within 7 days<br> prior to leukapheresis.<br><br> - Patients with a history of autoimmune disease resulting in end-organ injury are not<br> eligible unless attributable to primary disease which is target of this study<br><br> - Patient requires treatment with warfarin.<br><br> - Patients who have contraindication to the lymphodepletion chemotherapy regimen<br><br> - Patient received a live vaccine administration within 4 weeks prior to leukapheresis<br><br> - Patient is currently participating in another investigation treatment study, or has<br> participated in a study of an investigational agent within 4 weeks prior to<br> leukapheresis.<br><br> - Patients with clinically significant pulmonary dysfunction, as determined by medical<br> history and physical exam should undergo pulmonary function testing; those with a<br> forced expiratory volume at one second(FEV1) of = 65% or diffuse capacity lung for<br> carbon monoxide (DLCO; corrected) < 40% will be excluded<br><br> - Patients with history of other active malignancy within 1 year prior to enrollment.<br><br> - Patients with adequately resected basal or squamous cell carcinoma of the skin,<br> non-melanoma skin cancer or carcinoma in situ (e.g., skin, cervix, bladder, breast),<br> superficial bladder cancer, asymptomatic localized low grade prostate cancer for<br> which watch-and-wait approach is standard of care, or any other cancer that has been<br> in remission are eligible<br><br> - History of concomitant genetic syndrome associated with bone marrow failure such as<br> Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome<br><br> - Known human immunodeficiency virus (HIV) seropositivity or active hepatitis B or C<br> infection. A history of hepatitis B or C is permitted if the viral load is<br> undetectable by quantitative assay<br><br> - Ongoing uncontrolled serious infection, clinically significant cardiac disease<br> (i.e.,symptomatic congestive heart failure, myocardial infarction, cardiac<br> angioplasty or stenting, unstable angina pectoris, uncontrolled cardiac arrhythmia),<br> poorly controlled pulmonary disease (no clinically significant pleural effusion), or<br> psychiatric illness/social situations that would limit compliance with study<br> requirements within 12 months prior to enrollment.<br><br> - History of any central nervous system (CNS) disorder such as seizure disorder,<br> cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, any autoimmune<br> disease with CNS involvement, posterior reversible encephalopathy syndrome, or<br> cerebral edema<br><br> - History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months<br> prior to enrollment<br><br> - CNS lymphoma, untreated CNS metastases, leptomeningeal disease and/or carcinomatous<br> meningitis; patients with a history of brain metastases that are previously treated,<br> stable, and off systemic steroids for over 30 days prior to screening are eligible<br><br> - Patients that have not recovered from major acute infections and/or recent surgical<br> procedures<br><br> - Toxicities due to prior therapy must be stable and recovered to = grade 1 (except<br> for clinically non-significant toxicities such as alopecia)<br><br> - Patients, who in the opinion of the investigator, may not be able to comply with the<br> monitoring requirements of the study
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose (MTD) of PRGN-3007 (Group A);Maximum Tolerated Dose (MTD) of PRGN-3007 (Group B)
- Secondary Outcome Measures
Name Time Method Overall Response Rate;Disease Control Rate