CD19-Directed CAR-T Cell Therapy for the Treatment of Relapsed/Refractory B Cell Malignancies
Phase I Dose Escalation Trial of CD19 Directed Chimeric Antigen Receptor T Cell Therapy in the Treatment of Relapsed/Refractory B Cell Malignancies
3 other identifiers
interventional
25
1 country
1
Brief Summary
This phase I trial studies the effects of CD-19 directed chimeric antigen receptor (CAR)-T cell therapy for the treatment of patients with B cell malignancies that have come back (recurrent) or have not responded to treatment (refractory). CD-19 CAR-T cells use some of a patient's own immune cells, called T cells, to kill cancer. T cells fight infections and, in some cases, can also kill cancer cells. Some T cells are removed from the blood, and then laboratory, researchers will put a new gene into the T cells. This gene allows the T cells to recognize and possibly treat cancer. The new modified T cells are called the IC19/1563 treatment. IC19/1563 may help treat patients with relapsed/refractory B cell malignancies.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Oct 2022
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 12, 2021
CompletedFirst Posted
Study publicly available on registry
May 19, 2021
CompletedStudy Start
First participant enrolled
October 3, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 27, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 27, 2040
July 1, 2025
June 1, 2025
5.5 years
May 12, 2021
June 27, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Maximum tolerated dose (MTD)
MTD is defined as the dose level below the lowest dose that induces dose limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients).
90 days
Secondary Outcomes (7)
Proportion of patients who achieve a successful infusion without manufacturing failure or out of spec products
Up to 15.5 years
Overall response rate (ORR)
From a complete response (CR) or partial response (PR) noted as the objective status at any time after the start of CART19 infusion, assessed up to 15.5 years
Duration of response (DOR)
From CR or PR to the date of progression or death, assessed up to 15.5 years
Progression-free survival
From registration to disease progression or death, assessed up to 15.5 years
Rates of grade 3 or higher neurotoxicity
Up to 15.5 years
- +2 more secondary outcomes
Other Outcomes (6)
In vivo cellular kinetics profile of CAR19 cells
Up to 15.5 years
Serum/plasma levels of cytokines
Baseline up to 30 days
The total number of hospitalizations and ICU admissions
Up to 15.5 years
- +3 more other outcomes
Study Arms (1)
Treatment (cyclophosphamide, fludarabine, IC19/1563)
EXPERIMENTALPatients receive cyclophosphamide IV over 60 minutes and fludarabine IV over 30 minutes on days -5, -4, -3, or bendamustine IV over 10 minutes on days -4 and -3, and IC19/1563 IV on day 0. Patients also undergo bone marrow biopsy and aspiration, CT-PET or CT scans, MRI, and collection of blood and tissue samples throughout the trial.
Interventions
Given IV
Undergo collection of blood and tissue samples
Undergo bone marrow aspiration
Undergo bone marrow biopsy
Undergo CT
Given IV
Undergo MRI
Undergo CT/PET
Eligibility Criteria
You may qualify if:
- Age \>= 18 years
- Relapsed or refractory CD19+ B cell malignancies of the one of the following histopathology:
- Biopsy proven B-cell non-Hodgkin lymphoma (NHL) of any histopathology (including Richter Transformation of CLL); relapsed or refractory disease defined as:
- Two or more prior lines of therapy, at least one anthracycline containing regimen, unless intolerable. Exception: Patients with Richter transformation of CLL are eligible if they had \>= one prior treatment, including prior BTK inhibition
- Demonstration of progressive or stable disease by positron emission tomography/computed tomography (PET/CT) or CT criteria as the best response to the most recent chemotherapy regimen according to the revised Lugano Response Criteria for Malignant Lymphoma.
- Measurable disease defined as measurable by CT portion of a PET/CT: To be considered measurable, the must be at least one lesion that has a single diameter of (\>1.5 cm Note: Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy
- Biopsy proven SLL or flow cytometry proven CLL; relapsed disease defined as:
- \>= two prior lines of therapy, and/or \>= 6 months of second line prior BTK inhibition (e.g. venetoclax and ibrutinib). Exception: Patients in stable disease (SD) or partial response (PR) with a known ibrutinib resistance mutation (BTK or phospholipase Cgamma2) may be included even if on ibrutinib therapy for less than 6 months.
- Demonstration of progressive or stable disease by PET/CT or CT criteria according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL2018) criteria
- Measurable disease by CT portion of a PET/CT where at least one lesion has a single diameter of \>1.5 cm or peripheral blood absolute blood lymphocyte count (ALC) of \> 5000. Note: Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- Hemoglobin \>= 8.0 g/dL (=\< 14 days prior to registration)
- Absolute neutrophil count (ANC) \>= 500/mm\^3 (=\< 14 days prior to registration)
- Platelet count \>= 30,000/mm\^3 (=\< 14 days prior to registration)
- Total bilirubin =\< 2.0 mg/dL (with the exception of subjects with Gilbert's syndrome. Subjects with Gilbert's syndrome may be included if their total bilirubin is =\< 3.0 x upper limit of normal (ULN) and direct bilirubin =\< 1.5 x ULN) (=\< 14 days prior to registration)
- +10 more criteria
You may not qualify if:
- Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
- Pregnant persons
- Nursing persons
- Women of childbearing potential who are unwilling to employ highly effective contraception
- Sexually active males who are not willing to use contraception during the study and for \>= 12 months after IC19/1563 therapy
- Patients who are able to obtain market approved CD19 CAR T-cell therapies
- Live vaccine =\< 6 weeks prior to start of registration
- Autologous stem cell transplant =\< 6 weeks of registration
- History of allogenic stem cell transplant if was performed less than 100 days prior to registration, if patients have active graft-versus host disease (GVHD) or are if patients are on chronic immunosuppression. Patients with allogeneic transplantation more than 100 days prior to registration, with no active GVHD and who are not on immunosuppression are eligible
- History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with central nervous system (CNS) involvement
- Any form of primary immunodeficiency such as severe combined immunodeficiency disease
- Current need of systemic corticosteroid therapy, in doses over 20 mg /day of prednisone or equivalent forms of steroids
- History of severe immediate hypersensitivity reaction to CART19, stem cell infusion dimethyl sulfoxide (DMSO) or any of the CAR-T cryopreservation ingredients
- History of malignancy other than non-melanoma skin cancer, carcinoma in situ (e.g. cervix, bladder, breast) or early stage cancers (Stage I or II), unless disease free for \>= 2 years
- Clinically significant active infection (e.g. simple urinary tract infection \[UTI\], bacterial pharyngitis allowed) or currently receiving IV antibiotics or have received IV antibiotics =\< 7 days prior to registration. Note: prophylactic antibiotics, antivirals and antifungals are permitted
- +11 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Mayo Cliniclead
Study Sites (1)
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Saad J. Kenderian, M.D.
Mayo Clinic in Rochester
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 12, 2021
First Posted
May 19, 2021
Study Start
October 3, 2022
Primary Completion (Estimated)
March 27, 2028
Study Completion (Estimated)
March 27, 2040
Last Updated
July 1, 2025
Record last verified: 2025-06