Ignite Creation Date:
2024-05-06 @ 8:23 PM
Last Modification Date:
2024-10-26 @ 3:26 PM
Study NCT ID:
NCT06364423
Status:
RECRUITING
Last Update Posted:
2024-07-15
First Post:
2024-04-12
Brief Title:
Anti-CD19 Chimeric Antigen Receptor T-Cell Immunotherapy for Chronic Lymphocytic Leukemia CLL
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Phase III Trial of Anti-CD19 Chimeric Antigen Receptor T-Cell Immunotherapy for Chronic Lymphocytic Leukemia CLL
Status:
RECRUITING
Status Verified Date:
2024-09-20
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
Chronic lymphocytic leukemia CLL and small lymphocytic lymphoma SLL are blood cancers that affect certain white blood cells Advanced forms of these diseases are difficult to treat CD19 is a protein often found on the surfaces of these cancer cells Researchers can modify a persons own immune cells T cells to target CD19 When these modified T cells are returned to the body-a treatment called anti-CD19 chimeric antigen receptor CAR T cell therapy-they may help kill cancer cells
Objective
To test anti-CD19 CAR T cell therapy in people with CLL or SLL
Eligibility
People aged 18 years and older with CLL or SLL that has not been controlled with standard drugs
Design
Participants will be screened They will have imaging scans and tests of their heart function If a sample of tissue from their tumor is not available a new one may be taken the sample will be tested for CD19
Participants will receive a drug to reduce the leukemia cells in their blood Then they will undergo apheresis Blood will be taken from the body through a needle The blood will pass through a machine that separates out the T cells The remaining blood will be returned to the body through a different needle The collected T cells will be gene edited to make them attack cells with CD19
Participants will take drugs to prepare them for treatment for 3 days These drugs will start 5 days before the treatment Then their own modified CAR T cells will be returned to their bloodstream Participants will stay in the hospital for at least 9 days after the treatment
Follow-up visits will continue for 5 years
Chronic lymphocytic leukemia CLL and small lymphocytic lymphoma SLL are blood cancers that affect certain white blood cells Advanced forms of these diseases are difficult to treat CD19 is a protein often found on the surfaces of these cancer cells Researchers can modify a persons own immune cells T cells to target CD19 When these modified T cells are returned to the body-a treatment called anti-CD19 chimeric antigen receptor CAR T cell therapy-they may help kill cancer cells
Objective
To test anti-CD19 CAR T cell therapy in people with CLL or SLL
Eligibility
People aged 18 years and older with CLL or SLL that has not been controlled with standard drugs
Design
Participants will be screened They will have imaging scans and tests of their heart function If a sample of tissue from their tumor is not available a new one may be taken the sample will be tested for CD19
Participants will receive a drug to reduce the leukemia cells in their blood Then they will undergo apheresis Blood will be taken from the body through a needle The blood will pass through a machine that separates out the T cells The remaining blood will be returned to the body through a different needle The collected T cells will be gene edited to make them attack cells with CD19
Participants will take drugs to prepare them for treatment for 3 days These drugs will start 5 days before the treatment Then their own modified CAR T cells will be returned to their bloodstream Participants will stay in the hospital for at least 9 days after the treatment
Follow-up visits will continue for 5 years
Detailed Description:
Background
Improved treatments for relapsed and refractory chronic lymphocytic leukemia CLL are needed
T cells can be genetically modified to express chimeric antigen receptors CARs that specifically target malignancy-associated antigens
Autologous T cells genetically modified to express CARs targeting the B-cell antigen CD19 have caused complete remissions in patients with leukemia or lymphoma However there is no FDA-approved CAR T-cell product for CLL Responses to CAR T-cell therapy in CLL have historically been lower than in other B-cell malignancies
CD19 is uniformly expressed on CLL
CD19 is not expressed by normal cells except for B cells follicular dendritic cells and some plasma cells
We have constructed a novel gene therapy construct that encodes a fully-human anti-CD19 CAR
The conditioning regimen for this trial will include rituximab fludarabine and cyclophosphamide
Possible toxicities include cytokine-associated toxicities such as fever hypotension and neurological toxicities Elimination of normal B cells is probable and unknown toxicities are also possible
Primary objective Phase I
-Determine the safety of administering a novel conditioning regimen and T cells expressing the Hu19-CD828Z CAR to participants with advanced CLL
Primary objective Phase II
-Determine the overall response rate ORR of a novel conditioning regimen and T cells expressing the Hu19-CD828Z CAR for participants with advanced CLL
Eligibility
Participant must have CLL or small lymphocytic lymphoma SLL
Age 18 years of age at time of enrollment
Participant must have malignancy that is measurable on a CT scan or by flow cytometry of bone marrow or blood
Participant must have a creatinine of 15 mgdL or less and a normal cardiac ejection fraction
An ECOG performance status of 0-1 is required
No active infections are allowed including hepatitis B or hepatitis C
Absolute neutrophil count 1000microL platelet count 50000microL hemoglobin 8gdL
Serum ALT and AST less or equal to 3 times the upper limit of the institutional normal unless liver involvement by malignancy is demonstrated
At least 14 days must elapse between the time of any prior systemic treatment including corticosteroids and the first dose of protocol-required rituximab In addition 60 days must elapse from therapy with antibody-based treatments targeting CD19 and CAR T-cell infusion
Prior CAR T-cell therapy is not allowed
Demonstration of CD19 expression by the CLLSLL is required for eligibility
CD19 expression must be uniform Uniform CD19 expression is defined as no obvious CD19-negative CLLSLL being present
Design
This is a phase I dose-escalation trial with an expansion cohort Phase II portion
T cells obtained by leukapheresis will be genetically modified to express the Hu19-CD828Z CAR
Participants will receive 2 doses of rituximab and a lymphocyte-depleting chemotherapy conditioning regimen with the intent of decreasing the burden of CLL which might reduce toxicity and improve anti-leukemia outcomes
Rituximab will be given in 2 doses of 375 mgm2 for the first dose and 500 mgm2 for the second dose
The chemotherapy conditioning regimen is cyclophosphamide 500 mgm2 daily for 3 days and fludarabine 30 mgm2 daily for 3 days Fludarabine will be given on the same days as the cyclophosphamide
Three days after the chemotherapy ends participants will receive an infusion of CAR T cells
The initial dose level of this dose-escalation trial will be 10x106 CAR T cellskg of recipient bodyweight
The CAR T-cell cell dose administered will be escalated until a maximum tolerated dose or an optimal dose is determined
Following the T-cell infusion there is a mandatory 9-day inpatient hospitalization to monitor for toxicity
Outpatient follow-up is planned for 2 weeks and 1 2 3 4 6 9 and 12 months after the CAR T-cell infusion less frequent follow-up is required more than 1 year after infusion Long-term gene-therapy follow-up for a total of 15 years after infusion is required
Improved treatments for relapsed and refractory chronic lymphocytic leukemia CLL are needed
T cells can be genetically modified to express chimeric antigen receptors CARs that specifically target malignancy-associated antigens
Autologous T cells genetically modified to express CARs targeting the B-cell antigen CD19 have caused complete remissions in patients with leukemia or lymphoma However there is no FDA-approved CAR T-cell product for CLL Responses to CAR T-cell therapy in CLL have historically been lower than in other B-cell malignancies
CD19 is uniformly expressed on CLL
CD19 is not expressed by normal cells except for B cells follicular dendritic cells and some plasma cells
We have constructed a novel gene therapy construct that encodes a fully-human anti-CD19 CAR
The conditioning regimen for this trial will include rituximab fludarabine and cyclophosphamide
Possible toxicities include cytokine-associated toxicities such as fever hypotension and neurological toxicities Elimination of normal B cells is probable and unknown toxicities are also possible
Primary objective Phase I
-Determine the safety of administering a novel conditioning regimen and T cells expressing the Hu19-CD828Z CAR to participants with advanced CLL
Primary objective Phase II
-Determine the overall response rate ORR of a novel conditioning regimen and T cells expressing the Hu19-CD828Z CAR for participants with advanced CLL
Eligibility
Participant must have CLL or small lymphocytic lymphoma SLL
Age 18 years of age at time of enrollment
Participant must have malignancy that is measurable on a CT scan or by flow cytometry of bone marrow or blood
Participant must have a creatinine of 15 mgdL or less and a normal cardiac ejection fraction
An ECOG performance status of 0-1 is required
No active infections are allowed including hepatitis B or hepatitis C
Absolute neutrophil count 1000microL platelet count 50000microL hemoglobin 8gdL
Serum ALT and AST less or equal to 3 times the upper limit of the institutional normal unless liver involvement by malignancy is demonstrated
At least 14 days must elapse between the time of any prior systemic treatment including corticosteroids and the first dose of protocol-required rituximab In addition 60 days must elapse from therapy with antibody-based treatments targeting CD19 and CAR T-cell infusion
Prior CAR T-cell therapy is not allowed
Demonstration of CD19 expression by the CLLSLL is required for eligibility
CD19 expression must be uniform Uniform CD19 expression is defined as no obvious CD19-negative CLLSLL being present
Design
This is a phase I dose-escalation trial with an expansion cohort Phase II portion
T cells obtained by leukapheresis will be genetically modified to express the Hu19-CD828Z CAR
Participants will receive 2 doses of rituximab and a lymphocyte-depleting chemotherapy conditioning regimen with the intent of decreasing the burden of CLL which might reduce toxicity and improve anti-leukemia outcomes
Rituximab will be given in 2 doses of 375 mgm2 for the first dose and 500 mgm2 for the second dose
The chemotherapy conditioning regimen is cyclophosphamide 500 mgm2 daily for 3 days and fludarabine 30 mgm2 daily for 3 days Fludarabine will be given on the same days as the cyclophosphamide
Three days after the chemotherapy ends participants will receive an infusion of CAR T cells
The initial dose level of this dose-escalation trial will be 10x106 CAR T cellskg of recipient bodyweight
The CAR T-cell cell dose administered will be escalated until a maximum tolerated dose or an optimal dose is determined
Following the T-cell infusion there is a mandatory 9-day inpatient hospitalization to monitor for toxicity
Outpatient follow-up is planned for 2 weeks and 1 2 3 4 6 9 and 12 months after the CAR T-cell infusion less frequent follow-up is required more than 1 year after infusion Long-term gene-therapy follow-up for a total of 15 years after infusion is required
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 001599-C | None | None | None |