Refractory Chronic Lymphocytic Leukemia Clinical Trial
Official title:
Phase I/II Study of Dual CD19-CD22 Chimeric Antigen Receptor (CAR) T Cells in Patients With Advanced CD19+ CD22+ Lymphoid Malignancies
Verified date | August 2023 |
Source | M.D. Anderson Cancer Center |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This phase I/II trial studies the side effects and best dose of modified immune cells called CD19-CD22 chimeric antigen receptor (CAR) T cells in treating patients with CD19 positive(+), CD22+ B-acute lymphoblastic leukemia, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma that has come back (recurrent) or does not respond to treatment (refractory). T-cells are collected from the patient and genetic materials called "chimeric antigen receptors (CAR)" are transferred to the collected T-cells. The CAR T-cells are then infused back to the patient's body. Giving CD19- CD22 CAR T cells after chemotherapy may help to control the disease.
Status | Withdrawn |
Enrollment | 0 |
Est. completion date | November 16, 2022 |
Est. primary completion date | November 16, 2022 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 6 Months to 70 Years |
Eligibility | Inclusion Criteria: - Patients with relapsed/refractory B-acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), or non-Hodgkin's lymphoma (NHL) treated with at least two lines of therapy, and have persistent or progressed disease including positive minimal residual disease (MRD) - Patients may have received last cytotoxic chemotherapy at least 3 weeks prior to lymphodepleting chemotherapy - Patient may continue targeted therapy until 2 weeks before initiation of lymphodepleting chemotherapy with the exception of ibrutinib - Disease must be CD19 and/or CD22 positive by flow cytometry or immunohistochemistry - Karnofsky/Lansky performance scale > 70 - Total bilirubin less than < 1.5 mg/dL except patients with Gilbert syndrome whose total bilirubin must be < 3.0mg/dL - Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT]) =< 2.5 X upper limit of normal (ULN) - Alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 5.0 ULN - Serum creatinine (as estimated by Cockcroft Gault) >= 60 cc/min - Cardiac ejection fraction >= 50% without evidence of pericardiac effusion as determined by echocardiogram (ECHO) or multigated acquisition scan (MUGA), no clinical significant electrocardiogram (ECG) findings - No clinical significant pleural effusion and baseline oxygen saturation >= 92% - Absolute lymphocyte count >= 100/ul - Be able to sign informed consent - All participants who are able to have children must practice effective birth control while on study. Acceptable forms of birth control for female patients include: birth control pills, patches, or injections, intrauterine device (IUD), diaphragm with spermicide, or condom with spermicide. Acceptable forms of birth control for male patients include condom with spermicide. If female participant becomes pregnant during the study, she will be taken off this study. If male participant fathers a child while on study, he must immediately notify his doctor - For patients with history of allogenic stem cell transplantation - Should not have active acute graft-versus-host disease (GVHD) grade >= 2 - Should not be on immunosuppressants such as tacrolimus, sirolimus, cyclosporine, mycophenolates for a minimum of a month from CD19-CD22 CAR T cell infusion - Should not be on more than physiologic dose of systemic steroid for adrenal insufficiency (prednisone equivalent 5mg/day) - Transplantation should be more than 2 months from CD19-CD22 CAR T cell infusion - Other cell therapy including CAR T cells, donor lymphocyte infusion, virus specific T cells, natural killer (NK) cells, etc should have 6 weeks of wash-out period from the CD19-CD22 CAR T cell infusion - For patients with history of central nervous system (CNS) disease, CNS disease must be treated prior to enrollment - For patients with prior treatment history of cell therapy such as other CAR T cells or CAR NK cells or NK cells, cell therapy should have a 6 weeks of wash-out period from CD19-CD22 CAR T cell infusion - Be able to consent long-term follow-up protocol PA17-0483 Exclusion Criteria: - Positive beta-human chorionic gonadotropin (hCG) in female of child bearing potential defined as not postmenopausal for 24 months or no previous surgical sterilization or lactating females - Known positive serology for human immunodeficiency virus (HIV) - Presence of active grade 3 or greater toxicity from the previous treatment - Presence of active fungal, bacterial, viral, or other infection requiring IV antibiotics for management - Presence of active neurologic disorders - Concomitant use of other investigational agents - Current use of corticosteroid more than physiological dose for adrenal insufficiency (prednisone equivalent at a dose higher than 10 mg/day) - Presence of active CNS disease |
Country | Name | City | State |
---|---|---|---|
United States | M D Anderson Cancer Center | Houston | Texas |
Lead Sponsor | Collaborator |
---|---|
M.D. Anderson Cancer Center | National Cancer Institute (NCI) |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Immune reconstitution | These longitudinal values will be evaluated graphically and cross-tabulated with dose. | Up to 1 year post T-cell infusion | |
Other | Persistence of CAR T-cells | These longitudinal values will be evaluated graphically and cross-tabulated with dose. | Up to 1 year post T-cell infusion | |
Primary | Optimal chimeric antigen receptor (CAR) T cell dose level | Dose-finding will be done using the sequentially adaptive phase I-II EffTox method. | Up to 30 days | |
Primary | Incidence of adverse events (adverse events) | Toxicity is defined as a grade 3, 4, or 5 cytokine release syndrome, neurotoxicity, or National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 with onset within 30 days of cell infusion. Adverse events that are considered disease-related (not suspected of relationship to CD19-CD22 -CAR T cells) will not be considered dose-limiting toxicities. Only those AEs that occur during the first 30 days after infusion, which are suspected to be related to conditioning lymphodepletion chemotherapy regimen and/or CD19 -CD22-CAR T cells (any component of the treatment regimen), and meet the following criteria, will be used in the definition of toxicity. Hematologic toxicities will not be considered in the definition of toxicity, as pancytopenia is a common toxicity with this regimen. | Up to 30 days | |
Primary | Efficacy in complete response (CR) or partial response | Efficacy is defined as the patient being alive and in complete response (CR) or partial response (PR) at day 30 post cell infusion. | Day 30 post cell infusion | |
Secondary | Progression-free survival | Unadjusted distributions of the time-to-event outcomes will be estimated using the method of Kaplan and Meier and their relationship to prognostic covariates and T-cell dose level will be evaluated by Bayesian piecewise exponential survival regression. | Up to 1 year post T-cell infusion | |
Secondary | Overall survival | Unadjusted distributions of the time-to-event outcomes will be estimated using the method of Kaplan and Meier and their relationship to prognostic covariates and T-cell dose level will be evaluated by Bayesian piecewise exponential survival regression. | Up to 1 year post T-cell infusion |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT02948283 -
Metformin Hydrochloride and Ritonavir in Treating Patients With Relapsed or Refractory Multiple Myeloma or Chronic Lymphocytic Leukemia
|
Phase 1 | |
Completed |
NCT03045328 -
Venetoclax and Ibrutinib in Patients With Relapsed/Refractory CLL or SLL
|
Phase 2 | |
Terminated |
NCT02109224 -
Ibrutinib in Treating Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma in Patients With HIV Infection
|
Phase 1 | |
Active, not recruiting |
NCT01369849 -
Akt Inhibitor MK2206, Bendamustine Hydrochloride, and Rituximab in Treating Patients With Relapsed Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
|
Phase 1/Phase 2 | |
Completed |
NCT01233921 -
Palifermin in Preventing Chronic Graft-Versus-Host Disease in Patients Who Have Undergone Donor Stem Cell Transplant for Hematologic Cancer
|
N/A | |
Completed |
NCT01093586 -
Donor Umbilical Cord Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
|
Phase 2 | |
Terminated |
NCT00387426 -
Sunitinib in Treating Patients With Idiopathic Myelofibrosis
|
Phase 2 | |
Completed |
NCT00078858 -
Mycophenolate Mofetil and Cyclosporine in Reducing Graft-Versus-Host Disease in Patients With Hematologic Malignancies or Metastatic Kidney Cancer Undergoing Donor Stem Cell Transplant
|
Phase 1/Phase 2 | |
Completed |
NCT00053963 -
FR901228 in Treating Children With Refractory or Recurrent Solid Tumors or Leukemia
|
Phase 1 | |
Completed |
NCT00006226 -
Thalidomide in Treating Patients With Relapsed Chronic Lymphocytic Leukemia
|
Phase 2 | |
Completed |
NCT00005803 -
Autologous Stem Cell Transplant Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoma
|
Phase 1/Phase 2 | |
Completed |
NCT00003196 -
Low-Dose Total Body Irradiation and Donor Peripheral Blood Stem Cell Transplant Followed by Donor Lymphocyte Infusion in Treating Patients With Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, or Multiple Myeloma
|
N/A | |
Active, not recruiting |
NCT04230304 -
Daratumumab and Ibrutinib for the Treatment of Relapsed or Refractory Chronic Lymphocytic Leukemia, DIRECT Study
|
Phase 2 | |
Recruiting |
NCT04007029 -
Modified Immune Cells (CD19/CD20 CAR-T Cells) in Treating Patients With Recurrent or Refractory B-Cell Lymphoma or Chronic Lymphocytic Leukemia
|
Phase 1 | |
Recruiting |
NCT04892277 -
CD19-Directed CAR-T Cell Therapy for the Treatment of Relapsed/Refractory B Cell Malignancies
|
Phase 1 | |
Completed |
NCT01588015 -
Vaccine Therapy in Preventing Cytomegalovirus Infection in Patients With Hematological Malignancies Undergoing Donor Stem Cell Transplant
|
Phase 1 | |
Active, not recruiting |
NCT04578600 -
CC-486, Lenalidomide, and Obinutuzumab for the Treatment of Recurrent or Refractory CD20 Positive B-cell Lymphoma
|
Phase 1 | |
Completed |
NCT02240719 -
Everolimus and Bendamustine Hydrochloride in Treating Patients With Relapsed or Refractory Hematologic Cancer
|
Phase 1 | |
Completed |
NCT01441882 -
Dasatinib in Treating Patients With Chronic Lymphocytic Leukemia
|
Phase 2 | |
Terminated |
NCT01408043 -
Etoposide, Filgrastim, and Plerixafor in Improving Stem Cell Mobilization in Treating Patients With Non-Hodgkin Lymphoma
|
N/A |