ACTIVE_NOT_RECRUITING

huCART19-IL18 in CD19+ Cancers

Conditions

Chronic Lymphocytic Leukemia Non-hodgkin Lymphoma Acute Lymphoblastic Leukemia CLL NHL CAR-T cells

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this study is to evaluate the safety and feasibility of huCART19-IL18 cells in patients with relapsed or refractory CD19+ cancers.

Official Title

Phase I Trial of huCART19-IL18 Cells in Patients With Relapsed or Refractory CD19+ Cancers

Quick Facts

Study Start:2021-05-06

Study Completion:2036-05

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT04684563

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Signed informed consent form 2. Documentation of CD19 expression on malignant cells by flow cytometry/IHC from a CLIA certified laboratory 3. Patients with relapsed disease after prior allogeneic SCT must meet the following criteria: 4. Adequate organ function defined as: 5. Evidence of active disease within 12 weeks of physician-investigator confirmation of eligibility. . 6. Male or female age ≥ 18 years. 7. ECOG Performance Status that is either 0 or 1. 8. Subjects of reproductive potential must agree to use acceptable birth control methods. 9. Disease-specific criteria: 1. Relapsed/refractory disease after at least 2 prior lines of appropriate therapy; OR 2. Relapsed/refractory disease after autologous SCT; OR 3. Relapsed/refractory disease after allogeneic SCT. ii. Follicular lymphoma 1. Patients must have either relapsed after, or be ineligible for, prior commercial CAR T cell therapy; AND 2. Received at least 2 prior lines of appropriate therapy (not including single agent monoclonal antibody therapy) and progressed within 2 years after second or higher line of therapy. 1. Patients must have either failed standard of care CAR T cell therapy (e.g., Tecartus™, etc) or other investigational CAR T cell product, OR be ineligible for standard of care Tecartus™; and 2. Patients must also meet one of the following criteria: 1. Relapsed/refractory disease after at least 2 prior lines of appropriate therapy, including a BTK inhibitor. Single-agent monoclonal antibody therapy does not count towards prior lines of therapy; OR 2. Relapsed/refractory disease after prior autologous SCT; OR 3. Relapsed/refractory disease after prior allogeneic SCT. 1. Patients with relapsed/refractory disease after at least 2 prior lines of appropriate therapy; AND 2. Patients must have previously received or be intolerant to an approved BTK inhibitor and venetoclax, unless a BTK inhibitor or venetoclax is contraindicated. 1. Recurrent disease in the blood or bone marrow identified morphologically, by IHC or flow; OR 2. Isolated CNS disease. Note: Patients with prior/current history of CNS3 disease will only be eligible for treatment if the CNS disease is responsive to therapy; OR 3. Recurrent extramedullary disease at other (non-CNS) sites if disease response can be assessed radiographically. Note: Patients with recurrent extramedullary disease do not need to have detectable blood or bone marrow involvement; OR 4. Any relapse after allogeneic SCT; OR 5. Patients with refractory disease as defined by one of the following: 1. Failure to achieve remission (\<5% bone marrow blasts or ongoing extramedullary or CNS disease) after 2 cycles of induction chemotherapy; OR 2. Patients that achieve remission but remain MRD+ after ≥2 cycles of induction chemotherapy.	1. Active hepatitis B, active hepatitis C, or other active, uncontrolled infection. 2. Class III/IV cardiovascular disability according to the New York Heart Association Classification. 3. Clinically apparent arrhythmia or arrhythmias that are not stable on medical management within two weeks of physician-investigator confirmation of eligibility. 4. Active acute or chronic GVHD requiring systemic therapy. 5. Dependence on systemic steroids or immunosuppressant medications. For additional details regarding use of steroid and immunosuppressant medications. 6. RETIRED WITH PROTOCOL AMENDMENT V7 7. Receipt of prior huCART19 therapy. 8. CNS disease as defined by disease-cohort as follows: 1. NHL/CLL Patients: Active CNS disease. Note: Patients with a history of CNS involvement that was successfully treated are eligible. A CNS evaluation is only required for eligibility if a subject is experiencing signs/symptoms of CNS involvement. 2. ALL Patients: CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity. 9. Pregnant or nursing (lactating) women. 10. Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, and unrelated to their cancer or previous cancer treatment. 11. Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.

Inclusion Criteria

Exclusion Criteria

1. Signed informed consent form
2. Documentation of CD19 expression on malignant cells by flow cytometry/IHC from a CLIA certified laboratory
3. Patients with relapsed disease after prior allogeneic SCT must meet the following criteria:
4. Adequate organ function defined as:
5. Evidence of active disease within 12 weeks of physician-investigator confirmation of eligibility. .
6. Male or female age ≥ 18 years.
7. ECOG Performance Status that is either 0 or 1.
8. Subjects of reproductive potential must agree to use acceptable birth control methods.
9. Disease-specific criteria:
1. Relapsed/refractory disease after at least 2 prior lines of appropriate therapy; OR
2. Relapsed/refractory disease after autologous SCT; OR
3. Relapsed/refractory disease after allogeneic SCT. ii. Follicular lymphoma
1. Patients must have either relapsed after, or be ineligible for, prior commercial CAR T cell therapy; AND
2. Received at least 2 prior lines of appropriate therapy (not including single agent monoclonal antibody therapy) and progressed within 2 years after second or higher line of therapy.
1. Patients must have either failed standard of care CAR T cell therapy (e.g., Tecartus™, etc) or other investigational CAR T cell product, OR be ineligible for standard of care Tecartus™; and
2. Patients must also meet one of the following criteria:
1. Relapsed/refractory disease after at least 2 prior lines of appropriate therapy, including a BTK inhibitor. Single-agent monoclonal antibody therapy does not count towards prior lines of therapy; OR
2. Relapsed/refractory disease after prior autologous SCT; OR
3. Relapsed/refractory disease after prior allogeneic SCT.
1. Patients with relapsed/refractory disease after at least 2 prior lines of appropriate therapy; AND
2. Patients must have previously received or be intolerant to an approved BTK inhibitor and venetoclax, unless a BTK inhibitor or venetoclax is contraindicated.
1. Recurrent disease in the blood or bone marrow identified morphologically, by IHC or flow; OR
2. Isolated CNS disease. Note: Patients with prior/current history of CNS3 disease will only be eligible for treatment if the CNS disease is responsive to therapy; OR
3. Recurrent extramedullary disease at other (non-CNS) sites if disease response can be assessed radiographically. Note: Patients with recurrent extramedullary disease do not need to have detectable blood or bone marrow involvement; OR
4. Any relapse after allogeneic SCT; OR
5. Patients with refractory disease as defined by one of the following:
1. Failure to achieve remission (\<5% bone marrow blasts or ongoing extramedullary or CNS disease) after 2 cycles of induction chemotherapy; OR
2. Patients that achieve remission but remain MRD+ after ≥2 cycles of induction chemotherapy.

1. Active hepatitis B, active hepatitis C, or other active, uncontrolled infection.
2. Class III/IV cardiovascular disability according to the New York Heart Association Classification.
3. Clinically apparent arrhythmia or arrhythmias that are not stable on medical management within two weeks of physician-investigator confirmation of eligibility.
4. Active acute or chronic GVHD requiring systemic therapy.
5. Dependence on systemic steroids or immunosuppressant medications. For additional details regarding use of steroid and immunosuppressant medications.
6. RETIRED WITH PROTOCOL AMENDMENT V7
7. Receipt of prior huCART19 therapy.
8. CNS disease as defined by disease-cohort as follows:
1. NHL/CLL Patients: Active CNS disease. Note: Patients with a history of CNS involvement that was successfully treated are eligible. A CNS evaluation is only required for eligibility if a subject is experiencing signs/symptoms of CNS involvement.
2. ALL Patients: CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity.
9. Pregnant or nursing (lactating) women.
10. Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, and unrelated to their cancer or previous cancer treatment.
11. Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.

Contacts and Locations

Principal Investigator

Jakub Svoboda, MD

PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Study Locations (Sites)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104

United States

Collaborators and Investigators

Sponsor: University of Pennsylvania

Jakub Svoboda, MD, PRINCIPAL_INVESTIGATOR, University of Pennsylvania

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-05-06

Study Completion Date2036-05

Study Record Updates

Study Start Date2021-05-06

Study Completion Date2036-05

Terms related to this study

Keywords Provided by Researchers

CLL
NHL
CAR-T cells

Additional Relevant MeSH Terms

Chronic Lymphocytic Leukemia
Non-hodgkin Lymphoma
Acute Lymphoblastic Leukemia