Ignite Creation Date:
2025-12-24 @ 11:18 PM
Ignite Modification Date:
2026-01-01 @ 9:29 PM
Study NCT ID:
NCT04815356
Status:
RECRUITING
Last Update Posted:
2025-11-10
First Post:
2021-03-24
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Phase I Study of Anti-CD22 Chimeric Receptor T Cells in Patients With Relapsed/Refractory Hairy Cell Leukemia and Variant
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
Phase I Study of Anti-CD22 Chimeric Receptor T Cells in Patients With Relapsed/Refractory Hairy Cell Leukemia and Variant
Status:
RECRUITING
Status Verified Date:
2025-11-06
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:
CAR (Chimeric Antigen Receptor) T cell therapy is a type of cancer treatment in which a person s T cells (a type of immune cell) are changed in a laboratory to recognize and attack cancer cells. Researchers want to see if this treatment can help people with hairy cell leukemia (HCL).
Objective:
To test whether it is safe to give anti-CD22 CAR T cells to people with HCL.
Eligibility:
Adults ages 18 and older with HCL (classic or variant type) who have already had, are unable to receive, or have refused other standard treatments for their cancer.
Design:
Participants will be screened with the following:
Medical history
Physical exam
Blood and urine tests
Biopsy sample
Electrocardiogram
Echocardiogram
Lung function tests
Imaging scans
Some screening tests will be repeated during the study.
Participants may need to have a catheter placed in a large vein.
Participants will have magnetic resonance imaging of the brain.
Participants will have a neurologic evaluation and fill out questionnaires.
Participants will have leukapheresis. Blood will be removed from the participant. A machine will divide whole blood into red cells, plasma, and lymphocytes. The lymphocytes will be collected. The remaining blood will be returned to the participant.
Participants will get infusions of chemotherapy drugs.
Participants will get an infusion of the anti-CD22 CAR T cells. They will stay at the hospital for 14 days. Then they will have visits twice a week for 1 month.
After treatment, participants will be followed closely for 6 months, and then less frequently for at least 5 years. Then they will have long-term follow-up for 15 years.
CAR (Chimeric Antigen Receptor) T cell therapy is a type of cancer treatment in which a person s T cells (a type of immune cell) are changed in a laboratory to recognize and attack cancer cells. Researchers want to see if this treatment can help people with hairy cell leukemia (HCL).
Objective:
To test whether it is safe to give anti-CD22 CAR T cells to people with HCL.
Eligibility:
Adults ages 18 and older with HCL (classic or variant type) who have already had, are unable to receive, or have refused other standard treatments for their cancer.
Design:
Participants will be screened with the following:
Medical history
Physical exam
Blood and urine tests
Biopsy sample
Electrocardiogram
Echocardiogram
Lung function tests
Imaging scans
Some screening tests will be repeated during the study.
Participants may need to have a catheter placed in a large vein.
Participants will have magnetic resonance imaging of the brain.
Participants will have a neurologic evaluation and fill out questionnaires.
Participants will have leukapheresis. Blood will be removed from the participant. A machine will divide whole blood into red cells, plasma, and lymphocytes. The lymphocytes will be collected. The remaining blood will be returned to the participant.
Participants will get infusions of chemotherapy drugs.
Participants will get an infusion of the anti-CD22 CAR T cells. They will stay at the hospital for 14 days. Then they will have visits twice a week for 1 month.
After treatment, participants will be followed closely for 6 months, and then less frequently for at least 5 years. Then they will have long-term follow-up for 15 years.
Detailed Description:
Background
* Hairy cell leukemia (HCL) is an indolent CD22+ B-cell leukemia comprising 2% of all leukemias. Most cases of HCL respond well to purine analog chemotherapy and harbor BRAF V600E mutation that can be considered for targeted treatment at the time of relapse. However, there are patients with high-risk HCL such as patients with BRAF wild type IGHV4-34 unmutated HCL who respond poorly to chemotherapy and have poor survival.
* HCL variant (HCLv), also brightly CD22+, resembles HCL morphologically but is more aggressive and responds poorly to standard purine analog chemotherapy. Patients have fewer options of targeted treatment partly due to wild type BRAF. We showed that the overall survival in patients progressed after cladribine-rituximab is less than three years.
* Moxetumomab pasudotox-tdfk is an anti-CD22 recombinant immunotoxin which in 2018 was FDA-approved for adult patients with relapsed/refractory HCL. However, there are patients with HCL and HCLv who progress after treatments with standard purine analog chemotherapy and moxetumomab pasudotox-tdfk, and in the case of classic HCL, even after BRAF +/- MEK inhibition. There is still an unmet need for new treatment options for those with relapsed/refractory disease.
* Adoptive cellular therapy with T-cells genetically modified using viral-based vectors to express chimeric antigen receptors (CAR) targeting the CD22 molecule have demonstrated dramatic clinical responses in patients with CD22+ acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL).
* Moxetumomab pasudotox-tdfk proved that CD22 is a potent target for HCL due to its ubiquitous expression in HCL and HCLv, and cellular therapy represents a promising target for those patients that have progressed after other treatments options with chemotherapy, immunotherapy and targeted therapy. This will be the first trial of anti-CD22 CAR T-cell therapy in the treatment of relapsed/refractory HCL and HCLv.
Objectives
* To assess the safety and feasibility of administering escalating doses of autologous anti-CD22-CAR (M971BBz) engineered T-cells in participants with HCL/HCLv following a cyclophosphamide/fludarabine lymphodepletion regimen.
* Explore whether the administration of anti-CD22-CAR engineered T-cells can mediate antitumor effects in HCL/HCLv.
Eligibility
* HCL/HCLv, after prior treatment with, ineligible for, refusal of, or inability to obtain 1) Rituximab given concurrently with or sequentially after purine analog, 2) moxetumomab pasudotox-tdft, and 3) BRAF-inhibition.
* Need for treatment, either 1) absolute neutrophil count (ANC) \<1/nL, 2) hemoglobin (Hgb) \<10g/dL, 3) Platelets \<100/nL, 4) HCL mass with short axis \> 2 cm outside or \>0.5 cm inside the central nervous system (CNS), 5) HCL/HCLv count \>5/nL in blood or \>25/mm\^3 in cerebrospinal fluid (CSF), 6) HCL/HCLv count doubling time \<6 months and increasing lytic or blastic bone lesions, 7) symptomatic splenomegaly.
-\>= 18 years of age.
* CD22 expression must be detected on greater than 80% of the malignant cells by flow cytometry
* No uncontrolled infection, cardiopulmonary dysfunction, or secondary malignancy requiring treatment.
* No chemotherapy, immunotherapy, or radiation therapy less than or equal to 2 weeks prior to apheresis.
Design
* Peripheral blood mononuclear cells (PBMC) will be obtained by leukapheresis, CD3+ cells enriched and cultured in the presence of anti-CD3/-CD28 beads followed by lentiviral vector supernatant containing the anti-CD22 (M971BBz) CAR.
* On Day -5 (cell infusion is Day 0), participants will begin lymphodepleting chemotherapy comprising fludarabine 30 mg/m2 on Days -5, -4, -3, and -2, and cyclophosphamide 500 mg/m2 on days -3 and -2.
* The CD22-CAR T-cells will be infused on Day 0, with up to a 7 day delay if cells are cryopreserved, if needed for resolution of clinical toxicities, to generate adequate cell numbers, or to facilitate scheduling.
* A Phase I cell dose escalation scheme will be performed primarily using 4 dose levels (1 x 10\^5; 3 x 10\^5, 1 x 10\^6, and 3 x 10\^6 transduced T-cells/kg.
* After 2 participants are enrolled at dose level 1 without dose limiting toxicity (DLT) or response, subsequent participants will each be enrolled at increasing dose levels until either DLT or complete response (CR) is observed, after which that dose level will be expanded. Once the maximum tolerated dose (or highest level evaluated) is reached, with 0-1 out of 6 having DLT, an additional 4 participants will be enrolled to provide further assessment of DLTs and for determining a preliminary assessment of the efficacy of the therapy in this participant population.
* Participants will be monitored for toxicity, response and T-cell persistence as well as other biologic correlates.
* Participants who achieve inadequate engraftment of transduced T-cells may receive a 2nd dose of CAR T-cells at a same or higher dose level, with the same or lower dose of lymphodepleting chemotherapy, with results not to affect the primary endpoint of the study.
* Accrual ceiling will be set at 27 to allow for a few inevaluable participants and screen failures.
* Hairy cell leukemia (HCL) is an indolent CD22+ B-cell leukemia comprising 2% of all leukemias. Most cases of HCL respond well to purine analog chemotherapy and harbor BRAF V600E mutation that can be considered for targeted treatment at the time of relapse. However, there are patients with high-risk HCL such as patients with BRAF wild type IGHV4-34 unmutated HCL who respond poorly to chemotherapy and have poor survival.
* HCL variant (HCLv), also brightly CD22+, resembles HCL morphologically but is more aggressive and responds poorly to standard purine analog chemotherapy. Patients have fewer options of targeted treatment partly due to wild type BRAF. We showed that the overall survival in patients progressed after cladribine-rituximab is less than three years.
* Moxetumomab pasudotox-tdfk is an anti-CD22 recombinant immunotoxin which in 2018 was FDA-approved for adult patients with relapsed/refractory HCL. However, there are patients with HCL and HCLv who progress after treatments with standard purine analog chemotherapy and moxetumomab pasudotox-tdfk, and in the case of classic HCL, even after BRAF +/- MEK inhibition. There is still an unmet need for new treatment options for those with relapsed/refractory disease.
* Adoptive cellular therapy with T-cells genetically modified using viral-based vectors to express chimeric antigen receptors (CAR) targeting the CD22 molecule have demonstrated dramatic clinical responses in patients with CD22+ acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL).
* Moxetumomab pasudotox-tdfk proved that CD22 is a potent target for HCL due to its ubiquitous expression in HCL and HCLv, and cellular therapy represents a promising target for those patients that have progressed after other treatments options with chemotherapy, immunotherapy and targeted therapy. This will be the first trial of anti-CD22 CAR T-cell therapy in the treatment of relapsed/refractory HCL and HCLv.
Objectives
* To assess the safety and feasibility of administering escalating doses of autologous anti-CD22-CAR (M971BBz) engineered T-cells in participants with HCL/HCLv following a cyclophosphamide/fludarabine lymphodepletion regimen.
* Explore whether the administration of anti-CD22-CAR engineered T-cells can mediate antitumor effects in HCL/HCLv.
Eligibility
* HCL/HCLv, after prior treatment with, ineligible for, refusal of, or inability to obtain 1) Rituximab given concurrently with or sequentially after purine analog, 2) moxetumomab pasudotox-tdft, and 3) BRAF-inhibition.
* Need for treatment, either 1) absolute neutrophil count (ANC) \<1/nL, 2) hemoglobin (Hgb) \<10g/dL, 3) Platelets \<100/nL, 4) HCL mass with short axis \> 2 cm outside or \>0.5 cm inside the central nervous system (CNS), 5) HCL/HCLv count \>5/nL in blood or \>25/mm\^3 in cerebrospinal fluid (CSF), 6) HCL/HCLv count doubling time \<6 months and increasing lytic or blastic bone lesions, 7) symptomatic splenomegaly.
-\>= 18 years of age.
* CD22 expression must be detected on greater than 80% of the malignant cells by flow cytometry
* No uncontrolled infection, cardiopulmonary dysfunction, or secondary malignancy requiring treatment.
* No chemotherapy, immunotherapy, or radiation therapy less than or equal to 2 weeks prior to apheresis.
Design
* Peripheral blood mononuclear cells (PBMC) will be obtained by leukapheresis, CD3+ cells enriched and cultured in the presence of anti-CD3/-CD28 beads followed by lentiviral vector supernatant containing the anti-CD22 (M971BBz) CAR.
* On Day -5 (cell infusion is Day 0), participants will begin lymphodepleting chemotherapy comprising fludarabine 30 mg/m2 on Days -5, -4, -3, and -2, and cyclophosphamide 500 mg/m2 on days -3 and -2.
* The CD22-CAR T-cells will be infused on Day 0, with up to a 7 day delay if cells are cryopreserved, if needed for resolution of clinical toxicities, to generate adequate cell numbers, or to facilitate scheduling.
* A Phase I cell dose escalation scheme will be performed primarily using 4 dose levels (1 x 10\^5; 3 x 10\^5, 1 x 10\^6, and 3 x 10\^6 transduced T-cells/kg.
* After 2 participants are enrolled at dose level 1 without dose limiting toxicity (DLT) or response, subsequent participants will each be enrolled at increasing dose levels until either DLT or complete response (CR) is observed, after which that dose level will be expanded. Once the maximum tolerated dose (or highest level evaluated) is reached, with 0-1 out of 6 having DLT, an additional 4 participants will be enrolled to provide further assessment of DLTs and for determining a preliminary assessment of the efficacy of the therapy in this participant population.
* Participants will be monitored for toxicity, response and T-cell persistence as well as other biologic correlates.
* Participants who achieve inadequate engraftment of transduced T-cells may receive a 2nd dose of CAR T-cells at a same or higher dose level, with the same or lower dose of lymphodepleting chemotherapy, with results not to affect the primary endpoint of the study.
* Accrual ceiling will be set at 27 to allow for a few inevaluable participants and screen failures.
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 |
|---|---|---|---|---|
| 21-C-0019 | None | None | View |