Trial Title:
P-CD19CD20-ALLO1 Allogeneic CAR-T Cells in the Treatment of Subjects With B Cell Malignancies
NCT ID:
NCT06014762
Condition:
Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
High-grade B-cell Lymphoma
Primary Mediastinal Large B-cell Lymphoma (PMBCL)
Transformed Follicular Lymphoma (tFL)
Follicular Lymphoma Grade 3B
Conditions: Official terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
P-CD19CD20-ALLO1
Description:
Single weight-based IV administration
Arm group label:
P-CD19CD20-ALLO1 CAR-T Cells (Arm LD 1000)
Arm group label:
P-CD19CD20-ALLO1 CAR-T Cells (Arm LD 750)
Arm group label:
P-CD19CD20-ALLO1 CAR-T Cells (Arm S)
Intervention type:
Drug
Intervention name:
Rimiducid
Description:
Single weight-based IV administration
Arm group label:
P-CD19CD20-ALLO1 CAR-T Cells (Arm LD 1000)
Arm group label:
P-CD19CD20-ALLO1 CAR-T Cells (Arm LD 750)
Arm group label:
P-CD19CD20-ALLO1 CAR-T Cells (Arm S)
Summary:
Phase 1 study comprised of open-label, dose escalation and expansion cohort study of
P-CD19CD20-ALLO1 allogeneic T stem cell memory (Tscm) CAR-T cells in subjects with
relapsed/refractory B cell malignancies
Detailed description:
Phase 1 study consisting of two parts. Part 1 is a weight-based dose escalation following
a 3+3 design of dose-escalating cohorts to define a maximum tolerated dose (MTD). Part 2
includes administration at a selected dose and LD regimen. After enrollment, subjects
will receive a lymphodepletion therapy regimen before administration of allogeneic CAR-T
cells, administered as a single dose. Treated subjects will undergo serial measurements
of safety, tolerability and response. Rimiducid may be administered.
Criteria for eligibility:
Criteria:
Inclusion Criteria
1. Must have signed written, informed consent.
2. Males or females ≥ 18 years of age.
3. Must have prior biopsy proven confirmed diagnosis of DLBCL NOS (including DLBCL
arising from indolent lymphomas), HGBL, PMBCL,and tFL or follicular lymphoma Grade
3B.
4. Diagnosis of the disease based on WHO 2016 (Swerdlow, 2016) criteria.
5. Subjects must have measurable disease as defined by Lugano 2016 criteria (Cheson,
2016).
6. Must have relapsed/refractory disease and have received adequate prior anti-cancer
therapy, as defined below:
a. Prior systemic chemotherapy must include a line of chemoimmunotherapy that
includes an anti-CD20 antibody, an anthracycline, and 1 or more of the following: i.
No response to first-line therapy (primary refractory disease). Refractory disease
(defined as SD, PD, PR or CR with relapse before 3 months).
ii. Progressive disease following two or more lines of therapy. However, SD as the
best response after at least 2 cycles of the last line of therapy with SD duration
no longer than 6 months from the last dose of therapy is also acceptable.
iii. Refractory post-autologous stem cell transplant (ASCT). Disease progression or
relapse occurring at less than or equal to 12 months of undergoing ASCT (must have
biopsy proven recurrence in relapsed patients). If salvage therapy is given
post-ASCT, the patient must have had no response to or relapsed after the last line
of therapy.
iv. Refractory disease (SD, PD, PR or CR with relapse before 3 months) or relapsed
disease (defined as CR/PR with relapse on, or after lasting at least 3 months but no
more than 12 months), to CD20 antibody and anthracycline containing first-line
therapy.
7. Must be willing to practice birth control from the time of Screening and throughout
the first year of the study after P-CD19CD20-ALLO1 administration (both males and
females of childbearing potential).
8. Must have a negative serum pregnancy test at Screening and a negative urine
pregnancy test within 3 days prior to initiating the lymphodepletion chemotherapy
regimen (females of childbearing potential).
9. Must be at least 90 days since ASCT, if performed.
10. Treatment with prior CD19 targeted therapy is allowed, provided the last dose was
administered at least 90 days before the start of P-CD19CD20-ALLO1 treatment in this
study. Must be at least 3 months since autologous CAR-T therapy if such therapy was
administered (medical monitor must approve prior CAR-T therapy or other prior T cell
targeted therapy).
11. Must have adequate vital organ function, defined as follows (or medical monitor
approval):
1. Serum creatinine ≤ 1.5 mg/dL or estimated creatinine clearance ≥ 30 mL/min as
calculated using the Cockcroft-Gault formula and not dialysis-dependent.
2. Adequate hematologic function, including:
i. Absolute neutrophil count (ANC) ≥ 1000/μL in the absence of growth factor support
(granulocyte colony stimulating factor [G-CSF] within 7 days or peg-G-CSF within 14
days) ii. Platelet count ≥ 50,000/μL in the absence of transfusion support (platelet
transfusion within 7 days) iii. Hemoglobin ≥ 8 g/dL in the absence of transfusion
support (red blood cell count or whole blood within 7 days) c. Aspartate
transaminase (AST) and alanine aminotransferase (ALT) ≤ 3 × the upper limit of
normal (ULN), and total bilirubin ≤ 2.0 mg/dL (unless there is a history of
Gilbert's Syndrome in which case bilirubin levels ≤ 3 mg/dL).
d. Left ventricular ejection fraction (LVEF) ≥ 45%. LVEF assessment must have been
performed within 4 weeks of enrollment.
12. Must have recovered from toxicities due to prior therapies to Grade ≤ 2 according to
the NCI CTCAE v5.0 criteria or to the subject's prior baseline.
13. Must have an ECOG performance status of 0 to 1.
Exclusion Criteria
1. Is pregnant or lactating.
2. Has inadequate venous access.
3. Has active hemolytic anemia, POEMS syndrome (polyneuropathy, organomegaly,
endocrinopathy, monoclonal protein, and skin changes), disseminated intravascular
coagulation, leukostasis, or amyloidosis.
4. Concurrent or previous other malignancy within 2 years of study entry, except
curatively treated malignancies including basal or squamous cell skin cancer,
prostate intraepithelial neoplasm, carcinoma in situ of the cervix, breast, or
Bowen's disease. Patients with other curatively treated malignancies with low risk
of recurrence not listed may also be considered eligible after review and approval
by the Sponsor medical monitor.
5. Has active autoimmune disease, such as psoriasis, multiple sclerosis, lupus,
rheumatoid arthritis, etc. (the medical monitor will determine if a disease is
active and autoimmune).
6. Has a history of significant central nervous system (CNS) disease, such as stroke,
epilepsy, primary CNS lymphoma, etc. (the medical monitor will determine if
significant).
7. Has an active systemic infection (e.g., causing fevers or requiring antimicrobial
treatment).
8. Has a history of hepatitis B virus (HBV), hepatitis C virus (HCV), human
immunodeficiency virus (HIV), or human T-lymphotropic virus (HTLV) infection, or any
immunodeficiency syndrome. Subjects with a history of treated hepatitis C can be
enrolled if negative by hepatitis C polymerase chain reaction (PCR) on multiple
occasions and with medical monitor approval.
9. Is positive for human herpes virus (HHV)-6 or HHV-7 infection by PCR at the
Screening Visit (subjects may be included in the study if they are HHV-6 or HHV-7
IgG antibody-positive but PCR-negative).
10. Has New York Heart Association (NYHA) Class III or IV heart failure, unstable
angina, or a history of myocardial infarction or significant arrhythmia (e.g.,
atrial fibrillation, sustained [> 30 seconds] ventricular tachyarrhythmias, etc.).
11. Has any psychiatric or medical disorder (e.g., cardiovascular, endocrine, renal,
gastrointestinal, genitourinary, immunodeficiency or pulmonary disorder not
otherwise specified) that would, in the opinion of the Investigator or medical
monitor, preclude safe participation in and/or adherence to the protocol (including
medical conditions or laboratory findings that indicate a significant probability of
not qualifying for or being unable to undergo, LD chemotherapy and/or CAR-T cell
administration).
12. Has received non-mAb anti-cancer medications within 2 weeks of the time of
initiating LD chemotherapy.
13. Has received mAb therapy within 4 weeks of initiating LD chemotherapy.
14. Has received immunosuppressive medications within 2 weeks of the time of
administration of P-CD19CD20-ALLO1, and/or expected to require them while on study
(the medical monitor will determine if a medication is considered
immunosuppressive.)
15. Has received systemic corticosteroid therapy > 5 mg/day of prednisone or equivalent
dose of another corticosteroid within 1 week or 5 half-lives (whichever is shorter)
of the administration of P-CD19CD20-ALLO1 or is expected to require it during the
course of the study. (Topical and inhaled steroids are permitted. Systemic
corticosteroids are contraindicated after receiving P-CD19CD20-ALLO1 cells outside
of study-specific guidance or medical monitor approval).
16. Has CNS metastases or CNS involvement (including leptomeningeal carcinomatosis,
cranial neuropathies or mass lesions, cauda equina syndrome, and spinal cord
compression).
17. Has a history of severe immediate hypersensitivity reaction to any of the agents
used in this study.
18. Has a history of having undergone allogeneic or xenogeneic transplant, or has
undergone autologous transplantation within 90 days. Subjects with prior history of
allogeneic stem cell transplant may be enrolled if they are not on immunosuppressive
medications and with medical monitor approval.
19. Has received prior allogeneic genetically modified cellular therapy or was treated
with experimental allogeneic cell therapy.
20. History or Grade ≥ 3 HLH/MAS or neurotoxicity with prior therapies (all symptoms of
HLH/MAS, neurotoxicity, or CRS from prior therapies must be resolved at the time of
enrollment).
21. Has positive DAT at Screening Visit (may be allowed with medical monitor approval).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of California San Diego
Address:
City:
La Jolla
Zip:
92093
Country:
United States
Status:
Recruiting
Facility:
Name:
Loma Linda University Cancer Center
Address:
City:
Loma Linda
Zip:
92354
Country:
United States
Status:
Not yet recruiting
Facility:
Name:
Wayne State - Karmanos Cancer Institute
Address:
City:
Detroit
Zip:
48201
Country:
United States
Status:
Recruiting
Facility:
Name:
UNC Lineberger Comprehensive Cancer Center
Address:
City:
Chapel Hill
Zip:
27599
Country:
United States
Status:
Recruiting
Facility:
Name:
University of Cincinnati
Address:
City:
Cincinnati
Zip:
45206
Country:
United States
Status:
Recruiting
Facility:
Name:
University of Oklahoma, Health Sciences Center
Address:
City:
Oklahoma City
Zip:
73104
Country:
United States
Status:
Recruiting
Facility:
Name:
Prisma Health - Upstate Cancer Institute
Address:
City:
Greenville
Zip:
29605
Country:
United States
Status:
Recruiting
Facility:
Name:
Vanderbilt University Medical Center
Address:
City:
Nashville
Zip:
37232
Country:
United States
Status:
Recruiting
Facility:
Name:
Baylor Scott & White Research Institute
Address:
City:
Dallas
Zip:
75204
Country:
United States
Status:
Recruiting
Start date:
April 16, 2024
Completion date:
March 2041
Lead sponsor:
Agency:
Poseida Therapeutics, Inc.
Agency class:
Industry
Collaborator:
Agency:
Roche-Genentech
Agency class:
Industry
Source:
Poseida Therapeutics, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06014762
