Ignite Creation Date:
2025-12-25 @ 3:01 AM
Ignite Modification Date:
2025-12-26 @ 1:41 AM
Study NCT ID:
NCT05797233
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-08-19
First Post:
2023-04-01
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Trial of Anti-CD19 and Anti-CD20 Bicistronic Chimeric Antigen Receptor T Cells for Treating B-Cell Malignancies
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Phase I Trial of Anti-CD19 and Anti-CD20 Bicistronic Chimeric Antigen Receptor T- Cells for Treating B-cell Malignancies
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-08-15
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:
About 23,000 people die from B-cell cancers in the US each year. These cancers, often called leukemia or lymphoma, affect a type of white blood cell called B cells. These cancers are difficult to treat, and the therapies used can have bad side effects. Researchers want to try a new type of treatment. This new treatment uses a patient s own immune cells (T cells) that are modified to carry genes (chimeric antigen receptor, or CAR T cells) to kill cancer cells.
Objective:
To test a treatment using CAR T cells in people with B-cell cancers.
Eligibility:
People aged 18 to 75 years with a B-cell cancer that has not been controlled with standard therapies.
Design:
Participants will be screened. They will have:
Blood and urine tests.
A needle will be inserted to draw a sample of tissue from inside the hip bone.
For some patients, a needle will be inserted into their lower back to get a sample of the fluid around their spinal cord.
A tumor biopsy might be needed.
Imaging scans.
Tests of their heart function.
Participants will undergo apheresis: Blood will be drawn from a needle in an arm. The blood will pass through a machine that separates out the T cells. The remaining blood will be returned to the body through a second needle.
Participants will receive 2 chemotherapy drugs once a day for 3 days.
Participants will be admitted to the hospital for at least 9 days. Their T cells, now modified, will be infused back into their bloodstream through a tube placed in a large vein.
Follow-up visits will continue for 5 years, but patients will need to stay in touch with the CAR treatment team for 15 year.
About 23,000 people die from B-cell cancers in the US each year. These cancers, often called leukemia or lymphoma, affect a type of white blood cell called B cells. These cancers are difficult to treat, and the therapies used can have bad side effects. Researchers want to try a new type of treatment. This new treatment uses a patient s own immune cells (T cells) that are modified to carry genes (chimeric antigen receptor, or CAR T cells) to kill cancer cells.
Objective:
To test a treatment using CAR T cells in people with B-cell cancers.
Eligibility:
People aged 18 to 75 years with a B-cell cancer that has not been controlled with standard therapies.
Design:
Participants will be screened. They will have:
Blood and urine tests.
A needle will be inserted to draw a sample of tissue from inside the hip bone.
For some patients, a needle will be inserted into their lower back to get a sample of the fluid around their spinal cord.
A tumor biopsy might be needed.
Imaging scans.
Tests of their heart function.
Participants will undergo apheresis: Blood will be drawn from a needle in an arm. The blood will pass through a machine that separates out the T cells. The remaining blood will be returned to the body through a second needle.
Participants will receive 2 chemotherapy drugs once a day for 3 days.
Participants will be admitted to the hospital for at least 9 days. Their T cells, now modified, will be infused back into their bloodstream through a tube placed in a large vein.
Follow-up visits will continue for 5 years, but patients will need to stay in touch with the CAR treatment team for 15 year.
Detailed Description:
Background:
* Improved treatments for a variety of treatment-resistant malignancies including B-cell lymphomas, and chronic lymphocytic leukemia (CLL) are needed.
* A particular need is development of new treatments for chemotherapy-refractory B- cell malignancies.
* 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. These results have established anti-CD19 CAR T- cells as an important therapy for relapsed lymphoma, but only about 40% of patients receiving anti-CD19 CAR T- cells have durable complete remissions.
* Most B-cell malignancies express CD19 and CD20, but expression of CD19 and CD20 can be lost or diminished.
* CD19 and CD20 are not expressed by normal cells except for B cells and some plasma cells.
* We have constructed a novel gene therapy construct that encodes a fully-human anti- CD19 CAR with a CD28 domain and a fully-human anti-CD20 CAR with a 4-1BB domain.
* T -cells expressing this CAR construct, called Hu1928-Hu20BB-Long, can specifically recognize CD19 and CD20-expressing target cells in vitro and eradicate CD19 or CD20-expressing tumors in mice.
* One CAR expressed in this CAR construct, Hu19-CD828Z has been tested in humans before. The other CAR in the total construct, Hu20-CD8BBZ-Long, has not been tested in humans before.
* 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.
Objective:
\- Determine the safety of administering T-cells expressing a novel fully-human anti- CD19 and anti-CD20 CAR construct to participant with advanced B-cell malignancies.
Eligibility:
* Participant must have any B-cell lymphoma, or CLL/small lymphocytic lymphoma (SLL), or Gray-zone lymphoma. Lower grade lymphomas transformed to diffuse large B-cell lymphoma (DLBCL) are potentially eligible.
* Age \>= 18 years of age and \<=75 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 1.5 mg/dL 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 \>=1000/microL, platelet count \>=50,000/microL, hemoglobin \>=8g/dL
* 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 protocol-required leukapheresis or CAR T-cell infusion. In addition, sixty days must elapse from therapy with antibodies targeting CD19 or CD20 and CAR T-cell infusion, and at least 180 days must elapse since any prior CAR T-cell therapy or checkpoint therapy.
* The participant s malignancy will need to be assessed for CD19 and C20 expression by flow cytometry or immunohistochemistry performed at the NIH. If unstained, paraffin- embedded bone marrow or lymphoma tissue sections are available from prior biopsies, these can be used to determine CD19 and CD20 expression by immunohistochemistry; otherwise, Participant will need to come to the NIH for a biopsy to determine CD19 and CD20 expression. The sample for CD19 and CD20 expression must come from a biopsy obtained after any CD19 or CD20-targeted therapies such as monoclonal antibodies if such antibodies or CAR T-cell therapies have been received by the Participant.
* Either CD19 or CD20 expression must be uniform . Uniform CD19 or CD20 expression is defined as no obvious lymphoma population lacking antigen expression can be present.
Design:
* This is a phase I dose-escalation trial
* T-cells obtained by leukapheresis will be genetically modified to express the Hu1928- Hu20BB-Long CAR construct.
* Participants will receive a lymphocyte-depleting chemotherapy conditioning regimen with the intent of enhancing the activity of the infused CAR-expressing T- cells.
* The chemotherapy conditioning regimen is cyclophosphamide 500 mg/m\^2 daily for 3 days and fludarabine 30 mg/m\^2 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 anti- CAR- expressing T- cells .
* The initial dose level of this dose-escalation trial will be 0.66x10\^6 CAR+ T- cells/kg of recipient bodyweight.
* The cell dose administered will be escalated until a maximum tolerated 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 a variety of treatment-resistant malignancies including B-cell lymphomas, and chronic lymphocytic leukemia (CLL) are needed.
* A particular need is development of new treatments for chemotherapy-refractory B- cell malignancies.
* 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. These results have established anti-CD19 CAR T- cells as an important therapy for relapsed lymphoma, but only about 40% of patients receiving anti-CD19 CAR T- cells have durable complete remissions.
* Most B-cell malignancies express CD19 and CD20, but expression of CD19 and CD20 can be lost or diminished.
* CD19 and CD20 are not expressed by normal cells except for B cells and some plasma cells.
* We have constructed a novel gene therapy construct that encodes a fully-human anti- CD19 CAR with a CD28 domain and a fully-human anti-CD20 CAR with a 4-1BB domain.
* T -cells expressing this CAR construct, called Hu1928-Hu20BB-Long, can specifically recognize CD19 and CD20-expressing target cells in vitro and eradicate CD19 or CD20-expressing tumors in mice.
* One CAR expressed in this CAR construct, Hu19-CD828Z has been tested in humans before. The other CAR in the total construct, Hu20-CD8BBZ-Long, has not been tested in humans before.
* 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.
Objective:
\- Determine the safety of administering T-cells expressing a novel fully-human anti- CD19 and anti-CD20 CAR construct to participant with advanced B-cell malignancies.
Eligibility:
* Participant must have any B-cell lymphoma, or CLL/small lymphocytic lymphoma (SLL), or Gray-zone lymphoma. Lower grade lymphomas transformed to diffuse large B-cell lymphoma (DLBCL) are potentially eligible.
* Age \>= 18 years of age and \<=75 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 1.5 mg/dL 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 \>=1000/microL, platelet count \>=50,000/microL, hemoglobin \>=8g/dL
* 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 protocol-required leukapheresis or CAR T-cell infusion. In addition, sixty days must elapse from therapy with antibodies targeting CD19 or CD20 and CAR T-cell infusion, and at least 180 days must elapse since any prior CAR T-cell therapy or checkpoint therapy.
* The participant s malignancy will need to be assessed for CD19 and C20 expression by flow cytometry or immunohistochemistry performed at the NIH. If unstained, paraffin- embedded bone marrow or lymphoma tissue sections are available from prior biopsies, these can be used to determine CD19 and CD20 expression by immunohistochemistry; otherwise, Participant will need to come to the NIH for a biopsy to determine CD19 and CD20 expression. The sample for CD19 and CD20 expression must come from a biopsy obtained after any CD19 or CD20-targeted therapies such as monoclonal antibodies if such antibodies or CAR T-cell therapies have been received by the Participant.
* Either CD19 or CD20 expression must be uniform . Uniform CD19 or CD20 expression is defined as no obvious lymphoma population lacking antigen expression can be present.
Design:
* This is a phase I dose-escalation trial
* T-cells obtained by leukapheresis will be genetically modified to express the Hu1928- Hu20BB-Long CAR construct.
* Participants will receive a lymphocyte-depleting chemotherapy conditioning regimen with the intent of enhancing the activity of the infused CAR-expressing T- cells.
* The chemotherapy conditioning regimen is cyclophosphamide 500 mg/m\^2 daily for 3 days and fludarabine 30 mg/m\^2 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 anti- CAR- expressing T- cells .
* The initial dose level of this dose-escalation trial will be 0.66x10\^6 CAR+ T- cells/kg of recipient bodyweight.
* The cell dose administered will be escalated until a maximum tolerated 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?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 001524-C | None | None | View |