- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03774654
CD19.CAR Allogeneic NKT for Patients With Relapsed or Refractory B-Cell Malignancies (ANCHOR)
Allogeneic Natural Killer T-Cells Expressing CD19 Specific Chimeric Antigen Receptor and Interleukin-15 in Relapsed or Refractory B-Cell Malignancies
This study is for patients who have lymphoma or leukemia that has come back or has not gone away after treatment. Because there is no standard treatment for this cancer, patients are being asked to volunteer for a gene transfer research study using special immune cells.
The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting disease, antibodies and immune cells. Antibodies are types of proteins that protect the body from bacteria and other diseases. Immune cells, also called lymphocytes, are special infection-fighting blood cells that can kill other cells including tumor cells. Both antibodies and lymphocytes have been used to treat patients with cancer. They have shown promise, but have not been strong enough to cure most patients.
The antibody used in this study is called anti-CD19. This antibody sticks to lymphoma cells because of a substance on the outside of the cells called CD19. CD19 antibodies have been used to treat people with lymphoma and leukemia. For this study, the anti-CD19 antibody has been changed so that instead of floating free in the blood it is now joined to the NKT cells, a special type of lymphocytes that can kill tumor cells but not very effectively on their own. When an antibody is joined to a T cell in this way it is called a chimeric receptor. Investigators have also found that NKT cells work better if proteins are added that stimulate lymphocytes, such as one called CD28. Adding the CD28 makes the cells last for a longer time in the body but maybe not long enough for them to be able to kill the lymphoma cells. It is believed that by adding an extra stimulating protein, called IL-15, the cells will have an even better chance of killing the lymphoma cells.
In this study the investigators are going to see if this is true by putting the anti-CD19 chimeric receptor with CD28 and the IL-15 into NKT cells grown from a healthy individual. These cells are called ANCHOR cells. These cells will be infused into patients that have lymphomas or leukemias that have CD19 on their surface. The ANCHOR cells are investigational products not approved by the Food and Drug Administration.
The purpose of this study is to find the biggest dose of ANCHOR cells that is safe, to see how long the ANCHOR cells last, to learn what their side effects are and to see whether this therapy might help people with lymphoma or leukemia.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Earlier, a healthy donor provided blood to make ANCHOR cells in the laboratory. These cells were grown and frozen for later use. To make the ANCHOR cells, the investigators took the donor blood and stimulated it with growth factors to make the NKT cells grow. To get the CD19 antibody, CD28 and IL-15 into the NKT cells, they were infected with a virus, called a retrovirus. This virus cannot grow and infect other cells, but delivered a new genetic message into the ANCHOR cells that provides the instructions for the cells to make the CD19 antibody, CD28 and IL-15. This new genetic message will also help the investigators to find the ANCHOR cells in the blood after they are injected. Because patients will have received cells with a new gene in them, patients will be followed for a total of 15 years to see if there are any long term side effects of gene transfer.
Patients will be assigned a dose of ANCHOR cells. This is a dose escalation study. This means that at the beginning, patients will be started on the lowest dose of ANCHOR cells. Once that dose schedule proves safe, the next group of patients will be started at a higher dose. This process will continue until all 3 dose levels are studied. If the side effects are too severe, the dose will be lowered or the infusions will be stopped.
In this study, patients will receive treatment with cyclophosphamide and fludarabine. These drugs will decrease the numbers of the patients own immune cells before the ANCHOR cells are infused.
The patient will be given an injection of ANCHOR cells into the vein through an IV at the assigned dose. Before receiving the injection, the patient may be given a dose of Benadryl and Tylenol. The injection will take about 20 minutes. The patient will then be monitored in the clinic for up to 2 hours. Certain patients with aggressive lymphomas will need to be admitted to the hospital for the first three days after receiving the cells. Patients will need to stay in Houston for 4 weeks after the ANCHOR cell infusion to monitor them for side effects. Patients will have follow-up visits 3 times per week at weeks 1, 2, 3, 4, and once during week 6; months 3, 6, 9, and 12; twice a year for 4 years and then once a year for the next 10 years - for a total of 15 years). Patients will also have scheduled disease evaluations after the ANCHOR cell infusion (at week 4 and then as clinically needed).
The treatment will be given by the Center for Cell and Gene Therapy in Texas Chidren's Hospital or Houston Methodist Hospital.
Medical tests before treatment--
Before being treated, the patient will receive a series of standard medical tests:
- Physical exam and History
- Blood tests to measure blood cells, kidney and liver function
- Measurements of tumor by scans and/or bone marrow studies
- A urine or serum pregnancy test, when applicable
Medical tests during and after treatment--
Patients will receive standard medical tests when getting the infusions and afterwards. The evaluations that will be done at these visits include:
- Physical exams and History
- Blood tests to measure blood cells, kidney and liver function
- Measurements of the tumor by scans at 4-6 weeks, 3 months, 6 months, 9 months and 12 months
- If you have disease in the bone marrow, measurements of your tumor by bone marrow studies at 8-12 weeks, 6 months, 9 months and 12 months after the infusion.
- To learn more about the way the ANCHOR cells are working and how long they last in the body, extra blood will be drawn. On the day patients receive the cells, blood will be taken before the cells are given and a few hours afterwards. Other blood will be drawn one week after the infusion, 2 weeks, 3 weeks (optional), 4 weeks, and 6 weeks after the infusion, at 3 months, at 6 months, at 9 months, at 1 year, twice a year for 4 years, then yearly for the next 10 years - for a total of 15 years.
During the time points listed above, if the ANCHOR cells are found in the patient's blood above a certain amount, an extra 5 mL of blood may need to be collected for additional testing.
If the patient has a biopsy of a lymph node, like a repeat tumor or bone marrow study, the investigators may ask to have a piece for research purposes.
Patients will receive supportive care for any acute or chronic toxicities, including blood components or antibiotics, and other intervention as appropriate.
Study Type
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Carlos Ramos, MD
- Phone Number: (832) 824-4817
- Email: caramos@bcm.edu
Study Contact Backup
- Name: Mahshid Azamian
- Phone Number: 832-824-7930
- Email: Mahshid.Azamian@bcm.edu
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- Recruiting
- Houston Methodist Hospital
-
Contact:
- Carlos Ramos, MD
- Phone Number: 832-824-4817
- Email: caramos@bcm.edu
-
Houston, Texas, United States, 77030
- Not yet recruiting
- Texas Children's Hospital
-
Contact:
- Carlos Ramos, MD
- Phone Number: 832-824-4817
- Email: caramos@bcm.edu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Treatment Inclusion Criteria:
- Diagnosis of CD19-positive B-cell lymphoma or leukemia (ALL or CLL).
The disease is:
Cohort A (non-ALL patients):
- Relapsed or refractory after two or more lines of therapy, including a CD20 antibody, if an indolent lymphoma.
- Relapsed or refractory after two or more lines of therapy, including ibrutinib and venetoclax, if CLL.
Relapsed or refractory after two or more lines of therapy, including a CD20 antibody and an anthracycline, and the patient is ineligible for autologous stem cell transplantation, if an aggressive or highly aggressive lymphoma.
- Ineligibility for autologous stem cell transplantation includes non-responsive disease after salvage therapy and failure to mobilize stem cells for transplant.
Cohort B (ALL patients)
a. Relapsed or refractory after two or more lines of therapy, if ALL.
- Measurable disease by current criteria (Lugano criteria for lymphomas, IWG criteria for CLL, and detectable disease for ALL).
- Age ≥ 3 and ≤75 years.
- Bilirubin < 2 times (3 times if Gilbert syndrome) upper limit of normal
- AST and ALT less than 5 times the upper limit of normal.
- Estimated GFR ≥ 50 mL/min.
- Pulse oximetry of ≥ 90% on room air
- Karnofsky or Lansky score of ≥ 70.
- Recovered from the acute toxic effects of all prior chemotherapy based on the enrolling physician's assessment (if some effects of chemotherapy are expected to last long term, patient is eligible if meeting other eligibility criteria).
- Life expectancy of greater than 12 weeks.
- Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after the study is concluded. The male partner should use a condom.
- Patients must sign an informed consent indicating that they are aware this is a research study and have been told of its possible benefits and toxic side effects. Patients or their guardians will be given a copy of the consent form.
Treatment Exclusion Criteria:
- Currently receiving any investigational agents or received any cellular therapies within the previous 6 weeks.
- History of hypersensitivity reactions to murine protein-containing products.
- History of grade 2 to 4 graft-versus-host disease (GVHD)
- Pregnant or lactating.
- Active infection with HIV or HTLV.
- Active infection with HBV or HCV.
- Uncontrolled active bacterial, fungal or other viral infection.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: CD19.CAR-aNKT cells (cohort A, non-ALL)
This cohort is for patients without refractory/relapsed B-cell NHL or leukemia (ALL).
Three dose levels will be evaluated.
Patients will also receive lymphodepletion chemotherapy consisting of cyclophosphamide and fludarabine followed by the CD19.CAR-aNKT cell infusion.
|
Patients will be given the T-cell product by intravenous injection (into the vein through an IV line) at the assigned dose. Dose Level 1: 1 x 10^7/m2. Dose Level 2: 3 x 10^7/m2. Dose Level 3: 1 x 10^8/m2. |
Experimental: CD19.CAR-aNKT cells (cohort B, ALL).
This cohort is for patients with refractory/relapsed B-cell NHL or leukemia (ALL).
Three dose levels will be evaluated.
Patients will also receive lymphodepletion chemotherapy consisting of cyclophosphamide and fludarabine followed by the CD19.CAR-aNKT cell infusion.
|
Patients will be given the T-cell product by intravenous injection (into the vein through an IV line) at the assigned dose. Dose Level 1: 1 x 10^7/m2. Dose Level 2: 3 x 10^7/m2. Dose Level 3: 1 x 10^8/m2. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Dose limiting toxicity (DLT) rate
Time Frame: 4 weeks post T cell infusion
|
DLT rate is defined as the proportion of subjects with DLT evaluated as per the NCI CTCAE v5.0 with the exception of CRS and neurological toxicities that are related to T-cell infusions.
GVHD will be graded according to the BMT CTN Technical Manual of Procedures v3.0.
|
4 weeks post T cell infusion
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Frequency of circulating CD19.CAR-aNKT cells transduced with the vector.
Time Frame: 6 weeks post T cell infusion
|
The frequency of the infused cells will be summarized at pre- and post-infusion time points to evaluate their expansion and persistence.
|
6 weeks post T cell infusion
|
Overall response rate according to the Lugano criteria for non-Hodgkin lymphomas (for NHL) and the IWG (for CLL), or the proportion of patients with morphologic CR (for ALL).
Time Frame: 4-6 weeks post T cell infusion
|
Overall response rate is defined as the proportion of subjects with best overall response of complete response (CR) or partial response (PR) according to the Lugano criteria for non-Hodgkin lymphomas (for NHL) and the IWG (for CLL), or the proportion of patients with morphologic CR (for ALL).
|
4-6 weeks post T cell infusion
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Carlos Ramos, MD, Baylor College of Medicine
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Leukemia, Lymphoid
- Leukemia
- Leukemia, B-Cell
- Neoplasms
- Lymphoma
- Lymphoma, B-Cell
- Lymphoma, Non-Hodgkin
- Leukemia, Lymphocytic, Chronic, B-Cell
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Cyclophosphamide
- Fludarabine
Other Study ID Numbers
- H-44526 ANCHOR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Refractory B-Cell Non-Hodgkin Lymphoma
-
National Cancer Institute (NCI)RecruitingRefractory B-Cell Non-Hodgkin Lymphoma | Refractory T-Cell Non-Hodgkin Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma | Recurrent Transformed Non-Hodgkin Lymphoma | Recurrent Non-Hodgkin Lymphoma | Refractory Non-Hodgkin Lymphoma | Recurrent T-Cell Non-Hodgkin Lymphoma | Recurrent Primary Cutaneous... and other conditionsUnited States
-
The Lymphoma Academic Research OrganisationActive, not recruitingRefractory Indolent Adult Non-Hodgkin Lymphoma | Refractory Mantle Cell Lymphoma | Diffuse Large B-Cell Lymphoma Refractory | Refractory Transformed B-cell Non-Hodgkin Lymphoma | Refractory Primary Mediastinal Large B-Cell Cell LymphomaFrance
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedRecurrent Hodgkin Lymphoma | Refractory Hodgkin Lymphoma | Recurrent Mantle Cell Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Refractory T-Cell Non-Hodgkin Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma | Recurrent T-Cell Non-Hodgkin Lymphoma | Refractory Mantle Cell LymphomaUnited States
-
Nathan DenlingerBristol-Myers SquibbRecruitingB-Cell Non-Hodgkin Lymphoma-Recurrent | Diffuse Large B-Cell Lymphoma-Recurrent | Follicular Lymphoma-Recurrent | High Grade B-Cell Lymphoma-Recurrent | Primary Mediastinal Large B-Cell Lymphoma-Recurrent | Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma-Recurrent and other conditionsUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)TerminatedRecurrent Hodgkin Lymphoma | Refractory Hodgkin Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Refractory T-Cell Non-Hodgkin Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma | Recurrent T-Cell Non-Hodgkin LymphomaUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingRefractory Hodgkin Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Refractory T-Cell Non-Hodgkin Lymphoma | Hematopoietic Cell Transplantation RecipientUnited States
-
National Cancer Institute (NCI)RecruitingRecurrent Hodgkin Lymphoma | Refractory Hodgkin Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma | Recurrent Diffuse Large B-Cell Lymphoma | Refractory Diffuse Large B-Cell LymphomaUnited States
-
Caribou Biosciences, Inc.RecruitingLymphoma | Lymphoma, Non-Hodgkin | B Cell Lymphoma | Non Hodgkin Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Relapsed Non Hodgkin Lymphoma | B Cell Non-Hodgkin's LymphomaUnited States, Australia, Israel
-
AIDS Malignancy ConsortiumNational Cancer Institute (NCI); Memorial Sloan Kettering Cancer CenterNot yet recruitingHIV Infection | Recurrent Diffuse Large B-Cell Lymphoma | Recurrent Primary Mediastinal (Thymic) Large B-Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | Refractory Primary Mediastinal (Thymic) Large B-Cell Lymphoma | Recurrent Non-Hodgkin Lymphoma | Refractory Non-Hodgkin Lymphoma | Recurrent... and other conditions
-
Academic and Community Cancer Research UnitedNational Cancer Institute (NCI)Active, not recruitingRefractory B-Cell Non-Hodgkin Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma | Recurrent Diffuse Large B-Cell Lymphoma | Recurrent Primary Mediastinal (Thymic) Large B-Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | Refractory Primary Mediastinal (Thymic) Large B-Cell Lymphoma | Recurrent... and other conditionsUnited States
Clinical Trials on CD19.CAR-aNKT cells
-
Athenex, Inc.RecruitingB-cell Lymphoma | CLL/SLL | ALL, Childhood | DLBCL - Diffuse Large B Cell Lymphoma | B-cell Leukemia | NHL, Relapsed, Adult | ALL, Adult B CellUnited States
-
Zhejiang UniversityYake Biotechnology Ltd.RecruitingNon-hodgkin Lymphoma,B CellChina
-
Zhejiang UniversityYake Biotechnology Ltd.RecruitingAcute Lymphoblastic Leukemia | Non-hodgkin Lymphoma,B CellChina
-
Zhejiang UniversityYake Biotechnology Ltd.RecruitingVasculitis | Amyloidosis | Autoimmune Hemolytic Anemia | POEMS SyndromeChina
-
Miltenyi Biomedicine GmbHRecruitingB-cell Lymphoma Refractory | B-cell Lymphoma Recurrent | Acute Lymphoblastic Leukemia Recurrent | Chronic Lymphocytic Leukemia Recurrent | Chronic Lymphocytic Leukemia RefractoryGermany
-
Miltenyi Biomedicine GmbHNot yet recruiting
-
Southwest Hospital, ChinaUnknownLymphoma, Large B-Cell, DiffuseChina
-
Zhejiang UniversityShanghai YaKe Biotechnology Ltd.Recruiting
-
Zhejiang UniversityShanghai YaKe Biotechnology Ltd.Not yet recruitingNon-hodgkin Lymphoma,B Cell | Acute Lymphoblastic Leukemia,B-CellChina
-
University College, LondonEnrolling by invitationMultiple MyelomaUnited Kingdom