CD19+ Acute Leukemia Clinical Trial
Official title:
Pediatric and Young Adult Leukemia Adoptive Therapy (PLAT)-02: A Phase 1/2 Feasibility and Safety Study of CD19-CAR T Cell Immunotherapy for CD19+ Leukemia
| Verified date | June 2023 |
| Source | Seattle Children's Hospital |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
Patients with relapsed or refractory leukemia often develop resistance to chemotherapy. For this reason, we are attempting to use T cells obtained directly from the patient, which can be genetically modified to express a chimeric antigen receptor (CAR). The CAR enables the T cell to recognize and kill the leukemic cell through the recognition of CD19, a protein expressed of the surface of the leukemic cell in patients with CD19+ leukemia. This is a phase 1/2 study designed to determine the maximum tolerated dose of the CAR+ T cells as well as to determine the efficacy. The phase 1 cohort is restricted to those patients who have already had an allogeneic hematopoietic cell transplant (HCT). The phase 2 is open to all patients regardless of having a history of HCT.
| Status | Active, not recruiting |
| Enrollment | 167 |
| Est. completion date | July 2036 |
| Est. primary completion date | August 10, 2021 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 1 Year to 26 Years |
| Eligibility | Inclusion Criteria: Patients must be =12 months of age and <27 years of age at the time of study enrollment. Must be =10kg Confirmed CD19+ leukemia recurrence defined as =0.01% disease in the marrow or isolated extramedullary disease following allogeneic HCT. [N.B. Study closed to enrollment of leukemia subjects] OR No prior history of allogeneic HCT (one of the following) - 2nd or greater relapse, with or without extramedullary disease (isolated extramedullary disease is eligible) - 1st marrow relapse at end of 1st month of re-induction with marrow having =0.01% blast disease, with or without extramedullary disease - Primary Refractory as defined as having M2 or M3 marrow after induction - Subject has indication for HCT but has been deemed ineligible OR CD19+ Non-Hodgkin Lymphoma (NHL) refractory or relapsed with no known curative therapies available [N.B. Study remains open to enrollment of lymphoma subjects] Patients with CNS involvement are eligible provided that they are asymptomatic and in the opinion of the study PI have a reasonable expectation that disease burden can be controlled in the interval between enrollment and T cell infusion. Patients that have a significant neurologic deterioration will be not be eligible for T cell infusion until alternate therapies result in neurological stabilization. Patients must have a Lansky performance status score of =50 or a Karnofsky score of = 50 for patients =16 years of age. Life Expectancy of >8 weeks Patients must be free from active GVHD and off immunosuppressive GVHD therapy for 4 weeks prior to enrollment. Recovered from acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy It must be at least 7 days since last chemotherapy was administered (this does not include intrathecal chemotherapy or maintenance chemotherapy) No systemic corticosteroids (unless physiologic replacement dosing) within 7 days of enrollment. No prior genetically modified cell therapy that is still detectable or virotherapy allowed. - Normal serum creatinine based on age/gender - Total bilirubin </3x ULN OR conjugated bilirubin </2mg/dl - ALT </5X ULN - SF of >28% by ECHO or EF >50% by MUGA - ALC of >/= 100 cells/ul - Pulse ox >/= 90% on room air Patient must have documented negative HIV antigen and antibody, Hepatitis B surface antigen, and Hepatitis C antibody within 3 months prior to enrollment. For patient with positive Hepatitis C Ab, negative PCR testing must be documented in order to be eligible. Patients must NOT have active clinically significant CNS dysfunction (including but not limited to such as uncontrolled seizure disorder, paresis, aphasia, cerebrovascular ischemia/hemorrhage, severe brain injuries, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination or movement disorder) Must agree to highly effective contraception during and for 12 months after T cell infusion. Patients must be able to tolerate apheresis procedure, including placement of temporary apheresis line if required. Patients must NOT have an active malignancy other than CD19+ leukemia. Patients must NOT have an active severe infection defined as: - A positive blood culture within 48 hours of study enrollment - A fever above 38.2 C AND clinical signs of infection within 48 hours of study enrollment Patients must NOT have any concurrent medical condition that, in the opinion of the PI or designee, would prevent the patient from undergoing protocol-based therapy. Patients with a primary immunodeficiency/ bone marrow failure syndrome are excluded from this trial. Research participant or parent/legal guardian must agree to participate in long-term follow-up for up to 15 years, if they are enrolled in the study and receive T-cell infusion. |
| Country | Name | City | State |
|---|---|---|---|
| United States | Children's Hospital Los Angeles | Los Angeles | California |
| United States | Children's Hospital Oakland | Oakland | California |
| United States | Seattle Children's Hospital | Seattle | Washington |
| Lead Sponsor | Collaborator |
|---|---|
| Seattle Children's Hospital |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of Participants Who Experienced an Adverse Event Meeting the Dose-Limiting Toxicity Definition | The safety of the T cell infusion at the maximum tolerated dose determined in Phase 1, and further characterized in Phase 2, will be described | Initial CAR T cell infusion through 30 days post infusion | |
| Primary | Number of Participants With an MRD Negative Complete Remission After Initial CAR T Cell Infusion | The efficacy of the T cell infusion will be estimated based on the number of participants who have an MRD negative bone marrow aspirate following the initial T cell infusion | Initial CAR T cell infusion through Day 63 post infusion assessment (+/- 14 days) | |
| Primary | Number of Participants Who Have a Releasable Cell Product Generated | The feasibility of manufacturing and releasing T cell products from pediatric and young adult patients with CD19+ relapsed or refractory leukemia | Up to 28 days per manufacturing attempt | |
| Secondary | Persistence of Functional CD19 CAR+ T Cells | Participants will be followed for 63 days to determine if the transferred T cells remain detectable in the blood and bone marrow | Initial CAR T Infusion through Day 63 post infusion assessment (+/- 14 days) | |
| Secondary | Number of Participants With Recrudescence or Development of Acute GVHD (Graft Versus Host Disease) Symptoms Post CAR T Infusion | Initial CAR T Infusion through Day 63 post infusion assessment (+/- 14 days) | ||
| Secondary | Number of Participants That Received Cetuximab Who Have T Cells Successfully Ablated | The efficacy of cetuximab to ablate the T cells will be measured by loss of detection of T cells and any associated toxicities as well as facilitating B cell recovery. | 3 years |