Trial Title:
Genetically Engineered Cells (EGFRt/19-28z/IL-12 CAR T Cells) for the Treatment of Relapsed or Refractory CD19+ Hematologic Malignancies
NCT ID:
NCT06343376
Condition:
Recurrent Chronic Lymphocytic Leukemia
Recurrent Diffuse Large B-Cell Lymphoma
Recurrent Follicular Lymphoma
Recurrent High Grade B-Cell Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Transformed Chronic Lymphocytic Leukemia
Recurrent Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma
Refractory Chronic Lymphocytic Leukemia
Refractory Diffuse Large B-Cell Lymphoma
Refractory Follicular Lymphoma
Refractory High Grade B-Cell Lymphoma
Refractory Mantle Cell Lymphoma
Refractory Transformed Chronic Lymphocytic Leukemia
Refractory Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma
Conditions: Official terms:
Lymphoma
Leukemia
Lymphoma, Follicular
Lymphoma, B-Cell
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Hematologic Neoplasms
Recurrence
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo tissue biopsy
Arm group label:
Cohort A (EGFRt/19- 28z/IL-12 CAR T cells)
Arm group label:
Cohort B (EGFRt/19- 28z/IL-12 CAR T cells, conditioning)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Cohort A (EGFRt/19- 28z/IL-12 CAR T cells)
Arm group label:
Cohort B (EGFRt/19- 28z/IL-12 CAR T cells, conditioning)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Bone Marrow Aspiration
Description:
Undergo bone marrow biopsy and aspiration
Arm group label:
Cohort A (EGFRt/19- 28z/IL-12 CAR T cells)
Arm group label:
Cohort B (EGFRt/19- 28z/IL-12 CAR T cells, conditioning)
Intervention type:
Procedure
Intervention name:
Bone Marrow Biopsy
Description:
Undergo bone marrow biopsy and aspiration
Arm group label:
Cohort A (EGFRt/19- 28z/IL-12 CAR T cells)
Arm group label:
Cohort B (EGFRt/19- 28z/IL-12 CAR T cells, conditioning)
Other name:
Biopsy of Bone Marrow
Other name:
Biopsy, Bone Marrow
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Cohort A (EGFRt/19- 28z/IL-12 CAR T cells)
Arm group label:
Cohort B (EGFRt/19- 28z/IL-12 CAR T cells, conditioning)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
Given IV
Arm group label:
Cohort B (EGFRt/19- 28z/IL-12 CAR T cells, conditioning)
Other name:
(-)-Cyclophosphamide
Other name:
2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
Other name:
Asta B 518
Other name:
B-518
Other name:
Carloxan
Other name:
Ciclofosfamida
Other name:
Ciclofosfamide
Other name:
Cicloxal
Other name:
Clafen
Other name:
Claphene
Other name:
CP monohydrate
Other name:
CTX
Other name:
CYCLO-cell
Other name:
Cycloblastin
Other name:
Cycloblastine
Other name:
Cyclophospham
Other name:
Cyclophosphamid monohydrate
Other name:
Cyclophosphamide Monohydrate
Other name:
Cyclophosphamidum
Other name:
Cyclophosphan
Other name:
Cyclophosphane
Other name:
Cyclophosphanum
Other name:
Cyclostin
Other name:
Cyclostine
Other name:
Cytophosphan
Other name:
Cytophosphane
Other name:
Cytoxan
Other name:
Fosfaseron
Other name:
Genoxal
Other name:
Genuxal
Other name:
Ledoxina
Other name:
Mitoxan
Other name:
Neosar
Other name:
Revimmune
Other name:
Syklofosfamid
Other name:
WR- 138719
Other name:
WR-138719
Intervention type:
Procedure
Intervention name:
Echocardiography
Description:
Undergo ECHO
Arm group label:
Cohort A (EGFRt/19- 28z/IL-12 CAR T cells)
Arm group label:
Cohort B (EGFRt/19- 28z/IL-12 CAR T cells, conditioning)
Other name:
EC
Intervention type:
Biological
Intervention name:
EGFRt/19-28z/IL-12 CAR T-lymphocytes
Description:
Given IV
Arm group label:
Cohort A (EGFRt/19- 28z/IL-12 CAR T cells)
Arm group label:
Cohort B (EGFRt/19- 28z/IL-12 CAR T cells, conditioning)
Intervention type:
Drug
Intervention name:
Fludarabine Phosphate
Description:
Given IV
Arm group label:
Cohort B (EGFRt/19- 28z/IL-12 CAR T cells, conditioning)
Other name:
2-F-ara-AMP
Other name:
9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
Other name:
Beneflur
Other name:
Fludara
Other name:
SH T 586
Intervention type:
Procedure
Intervention name:
Leukapheresis
Description:
Undergo leukapheresis
Arm group label:
Cohort A (EGFRt/19- 28z/IL-12 CAR T cells)
Arm group label:
Cohort B (EGFRt/19- 28z/IL-12 CAR T cells, conditioning)
Other name:
Leukocytopheresis
Other name:
Therapeutic Leukopheresis
Intervention type:
Procedure
Intervention name:
Multigated Acquisition Scan
Description:
Undergo MUGA
Arm group label:
Cohort A (EGFRt/19- 28z/IL-12 CAR T cells)
Arm group label:
Cohort B (EGFRt/19- 28z/IL-12 CAR T cells, conditioning)
Other name:
Blood Pool Scan
Other name:
Equilibrium Radionuclide Angiography
Other name:
Gated Blood Pool Imaging
Other name:
Gated Heart Pool Scan
Other name:
MUGA
Other name:
MUGA Scan
Other name:
Multi-Gated Acquisition Scan
Other name:
Radionuclide Ventriculogram Scan
Other name:
Radionuclide Ventriculography
Other name:
RNVG
Other name:
SYMA Scanning
Other name:
Synchronized Multigated Acquisition Scanning
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET
Arm group label:
Cohort A (EGFRt/19- 28z/IL-12 CAR T cells)
Arm group label:
Cohort B (EGFRt/19- 28z/IL-12 CAR T cells, conditioning)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron emission tomography (procedure)
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
PT
Summary:
This phase I trial tests the safety, side effects, and best dose of genetically
engineered cells called EGFRt/19-28z/IL-12 CAR T cells, and to see how they work in
treating patients with hematologic malignancies that makes a protein called CD19
(CD19-positive) that has come back after a period of improvement (relapsed) or that has
not responded to previous treatment (refractory). Chimeric Antigen Receptor (CAR) T-cell
Therapy is a type of treatment in which a patient's 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. Then the gene for a special receptor that binds to a certain
protein on the patient's cancer cells is added to the T cells in the laboratory. The
special receptor is called a chimeric antigen receptor (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. To improve the effectiveness of the modified T cells and to help the
immune system fight cancer cells better, the modified T cells given in this study will
include a gene that makes the T cells produce a cytokine (a molecule involved in
signaling within the immune system) called interleukin-12 (IL-12). The researchers think
that IL-12 may improve the effectiveness of the modified T cells, and it may also
strengthen the immune system to fight cancer. Giving EGFRt/19-28z/IL-12 CAR T cells may
be safe and tolerable in treating patients with relapsed or refractory CD19+ hematologic
malignancies.
Detailed description:
PRIMARY OBJECTIVE:
I. To determine the safety, toxicity and maximum tolerated dose (MTD) of
EGFRt/19-28z/IL-12 CAR T-lymphocytes (EGFRt/19-28z/IL-12 CAR T cells) in patients with
relapsed or refractory CD19+ aggressive hematologic malignancies.
SECONDARY OBJECTIVES:
I. To assess the anti-tumor efficacy of adoptively transferred EGFRt/19-28z/IL-12 T
cells.
II. To assess the in vivo persistence of adoptively transferred EGFRt/19-28z/IL-12 T
cells.
EXPLORATORY OBJECTIVES:
I. To describe the cellular and cytokine microenvironment following infusion of
adoptively transferred EGFRt/19-28z/IL-12 T cells.
II. To characterize endogenous anti-tumor immune responses following infusion of
adoptively transferred EGFRt/19-28z/IL-12 T cells.
III. To summarize levels of normal B cells and the incidence of B cell aplasia following
infusion of adoptively transferred EGFRt/19-28z/IL-12 T cells.
IV. To determine the proportion of evaluable patients who achieve minimal residual
disease (MRD)-negativity in peripheral blood and/or bone marrow.
V. To assess phenotype and in vitro function of end-of-production (EOP)
EGFRt/19-28z/IL-12 CAR T cells and phenotype at recovery following CAR T cell
administration.
OUTLINE: This is a dose-escalation study of EGFRt/19- 28z/IL-12 CAR T cells. Patients are
assigned to 1 of 2 cohorts.
COHORT A: Patients undergo leukapheresis prior to treatment. Patients receive EGFRt/19-
28z/IL-12 CAR T cells intravenously (IV) over 5 to 30 minutes on day 0. Patients also
undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening.
Patients also undergo computed tomography (CT) or positron emission tomography (PET) as
well as bone marrow biopsy and aspiration and blood sample collection throughout the
trial. Additionally, patients undergo a tissue biopsy during screening and on the trial.
COHORT B: Patients undergo leukapheresis prior to treatment and receive lymphodepletion
chemotherapy with cyclophosphamide IV over 2 hours and fludarabine IV over 30 minutes on
days -5, -4, and -3. Patients then receive EGFRt/19- 28z/IL-12 CAR T cells IV over 5 to
30 minutes on day 0. Patients also undergo ECHO or MUGA during screening. Patients also
undergo CT or PET as well as bone marrow biopsy and aspiration and blood sample
collection throughout the trial. Additionally, patients undergo a tissue biopsy during
screening and on the trial.
After completion of study treatment, patients are followed up weekly for 4 weeks, every 4
weeks until 24 months, every 3 months thereafter for 1 year, then annually for up to 5
years, followed by long-term follow up for up to 15 years.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients with relapsed refractory B Cell malignancies which commonly express CD-19.
- Eligible disease subtypes include the following:
- Patients with diffuse large B-cell lymphoma (de novo or diffuse large
B-cell lymphoma [DLBCL] transformed from an indolent lymphoma (follicular
lymphoma, chronic lymphocytic leukemia) or high grade B-cell Lymphoma
(HGBL):
- Relapsed or refractory DLBCL or high-grade B-cell lymphoma (HGBL)
following 2 or more prior chemoimmunotherapy regimens containing an
anthracycline and CD20-directed therapy following diagnosis of de
novo DLBCL/HGBL or DLBCL arising from indolent lymphoma and requiring
further treatment.
- Relapse following a single prior chemoimmunotherapy regimen
containing an anthracycline and CD20-directed therapy following
diagnosis of de novo DLBCL/HGBL or DLBCL arising from indolent
lymphoma and considered ineligible for high dose chemotherapy and
autologous stem cell rescue as determined by the investigator.
- Patients must have at least one fludeoxyglucose F-18 (FDG)-avid
(PET-avid) measurable lesion.
- Biopsy confirmation of relapsed of refractory DLBCL is required.
- Chronic lymphocytic leukemia after 2 lines of therapy including a BTKi
(bruton tyrosine kinase inhibitor).
- Mantle cell lymphoma after 2 lines of therapy. Patients must have
previously received chemoimmunotherapy and a prior BTK inhibitor.
- Follicular lymphoma after 2 lines of therapy. Patients must have
previously received chemoimmunotherapy and immunomodulatory agent.
- For cohort 1A specifically, patients must additionally have received a prior
CD19-targeted CAR T-cell therapy or not have an indication for a Food and Drug
Administration (FDA)-approved commercial CD19-targeted CAR T-cell therapy.
- For cohorts other than cohort 1A (and if needed, cohort -1), patients with an
indication for an FDA approved commercial CD19-targeted CAR T-cell therapy are
eligible following an informed consent discussion that reviews the risks and
benefits of the FDA-approved commercial CD19-targeted CAR T-cell therapy vs the
investigational product.
- Prior CD19-targeted therapies, including CAR T-cell therapy, does not exclude
participation; however, CD19 expression by immunohistochemical staining or flow
cytometry must be confirmed prior to enrollment for patients who have received such
therapies.
- Age ≥ 18 years of age.
- Creatinine Clearance > 30 mL/min (Cockroft-Gault equation).
- Direct bilirubin ≤ 2.0 mg/dL (unless related to disease).
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper
limit of normal (ULN) (unless related to disease).
- Adequate pulmonary function as assessed by ≥ 90% oxygen saturation on room air by
pulse oximetry.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
- Participants of child-bearing potential must agree to use adequate contraceptive
methods (e.g., hormonal or barrier method of birth control; abstinence) prior to
study entry. Should a woman become pregnant or suspect she is pregnant while she or
her partner is participating in this study, she should inform her treating physician
immediately. Patients of childbearing age should use effective contraception while
on this study and continue for 1 year after all treatment is finished.
- Participant must understand the investigational nature of this study and sign an
Independent Ethics Committee/Institutional Review Board approved written informed
consent form prior to receiving any study related procedure.
Exclusion Criteria:
- Pregnant or lactating patients.
- Impaired cardiac function (left ventricular ejection fraction [LVEF] < 40%) as
assessed by ECHO or MUGA scan during screening.
- Patients with active graft versus host disease following allogeneic hematopoietic
cell transplantation requiring systemic T cell suppressive therapy are ineligible.
- Patients with active autoimmune disease requiring systemic T cell suppressive
therapy are ineligible.
- Patients with following cardiac conditions will be excluded:
- New York Heart Association (NYHA) stage III or IV congestive heart failure.
- Myocardial infarction ≤ 6 months prior to enrollment.
- Any history of clinically significant ventricular arrhythmia or unexplained
syncope, not believed to be vasovagal in nature or due to dehydration.
- Patients with HIV are ineligible.
- Patients with active hepatitis B infection (as manifest by either detectable
hepatitis B virus deoxyribonucleic acid [DNA] by polymerase chain reaction [PCR]
and/or positivity for hepatitis B surface antigen) are ineligible.
- Patients with active hepatitis C infection (as manifest by detectable hepatitis C
virus ribonucleic acid [RNA] by PCR) are ineligible. Patients with detectable
antibodies to hepatitis C virus will be screened by PCR for evidence of active
infection.
- Patients with uncontrolled systemic fungal, bacterial, viral or other infection are
ineligible.
- Patients with any concurrent active malignancies as defined by malignancies
requiring any therapy other than expectant observation or hormonal therapy, with the
exception of squamous and basal cell carcinoma of skin.
- Patients with history or presence of clinically significant neurological disorders
such as epilepsy, generalized seizure disorder, severe brain injuries are
ineligible.
- Patients with primary central nervous system (CNS) disease are ineligible.
- Unwilling or unable to follow protocol requirements.
- Any other condition/issue which, in the opinion of the treating physician, would
make the patient ineligible for the study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Roswell Park Cancer Institute
Address:
City:
Buffalo
Zip:
14263
Country:
United States
Status:
Recruiting
Contact:
Last name:
Francisco J. Hernandez-ILizaliturri
Phone:
716-845-1642
Email:
Francisco.Hernandez@RoswellPark.org
Investigator:
Last name:
Francisco J. Hernandez-ILizaliturri
Email:
Principal Investigator
Start date:
November 15, 2024
Completion date:
June 15, 2029
Lead sponsor:
Agency:
Roswell Park Cancer Institute
Agency class:
Other
Source:
Roswell Park Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06343376
