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CD19.CAR Allogeneic NKT for Patients With Relapsed or Refractory B-Cell Malignancies (ANCHOR)

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ClinicalTrials.gov Identifier: NCT03774654
Recruitment Status : Not yet recruiting
First Posted : December 13, 2018
Last Update Posted : December 13, 2018
Sponsor:
Collaborators:
Center for Cell and Gene Therapy, Baylor College of Medicine
Texas Children's Hospital
The Methodist Hospital System
Information provided by (Responsible Party):
Carlos Ramos, Baylor College of Medicine

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Refractory B-Cell Non-Hodgkin Lymphoma Refractory B-Cell Small Lymphocytic Lymphoma Relapsed Adult ALL Relapsed CLL Relapsed Non Hodgkin Lymphoma Genetic: CD19.CAR-aNKT cells Drug: Cyclophosphamide Drug: Fludarabine Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Allogeneic Natural Killer T-Cells Expressing CD19 Specific Chimeric Antigen Receptor and Interleukin-15 in Relapsed or Refractory B-Cell Malignancies
Estimated Study Start Date : March 2019
Estimated Primary Completion Date : April 2022
Estimated Study Completion Date : March 2034


Arm Intervention/treatment
Experimental: CD19.CAR-aNKT cells
This is a single arm study. Four dose levels will be evaluated. Patients will also receive lymphodepletion chemotherapy consisting of cyclophosphamide and fludarabine followed by the CD19.CAR-aNKT cell infusion.
Genetic: CD19.CAR-aNKT cells

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. Dose Level 4: 3 x 10^8/m2.


Drug: Cyclophosphamide
Lymphodepletion chemotherapy. Patients will receive 3 daily doses of cyclophosphamide (500mg/m^2/day) finishing at least 24 hours before T-cell infusion. The drug will be given intravenously (through an IV needle).
Other Name: Cytoxan

Drug: Fludarabine
Lymphodepletion chemotherapy. Patients will receive 3 daily doses of fludarabine (30mg/m^2/day) finishing at least 24 hours before T-cell infusion. The drug will be given intravenously (through an IV needle).
Other Name: Fludara




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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).



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Treatment Inclusion Criteria:

  1. Diagnosis of CD19-positive B-cell lymphoma or leukemia (ALL or CLL).
  2. The disease is:

    1. Relapsed or refractory after two or more lines of therapy, including a CD20 antibody, if an indolent lymphoma or CLL.
    2. 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.
    3. Relapsed or refractory after two or more lines of therapy, if ALL.
  3. Measurable disease by current criteria.
  4. Age >17 and ≤75 years.
  5. Bilirubin less than 3 times the upper limit of normal.
  6. AST less than 5 times the upper limit of normal.
  7. Estimated GFR ≥ 50 mL/min.
  8. Pulse oximetry of ≥ 90% on room air
  9. Karnofsky or Lansky score of ≥ 70%.
  10. 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).
  11. Life expectancy of greater than 12 weeks.
  12. 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.
  13. 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:

  1. Currently receiving any investigational agents or received any cellular therapies within the previous 6 weeks.
  2. History of hypersensitivity reactions to murine protein-containing products.
  3. Pregnant or lactating.
  4. Active infection with HIV or HTLV.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03774654


Contacts
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Contact: Carlos Ramos, MD (832) 824-4817 caramos@bcm.edu

Locations
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United States, Texas
Houston Methodist Hospital Not yet recruiting
Houston, Texas, United States, 77030
Contact: Carlos Ramos, MD    832-824-4817    caramos@bcm.edu   
Texas Children's Hospital Not yet recruiting
Houston, Texas, United States, 77030
Contact: Carlos Ramos, MD    832-824-4817    caramos@bcm.edu   
Sponsors and Collaborators
Baylor College of Medicine
Center for Cell and Gene Therapy, Baylor College of Medicine
Texas Children's Hospital
The Methodist Hospital System
Investigators
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Principal Investigator: Carlos Ramos, MD Baylor College of Medicine

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Responsible Party: Carlos Ramos, Associate Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT03774654     History of Changes
Other Study ID Numbers: H-44526 ANCHOR
First Posted: December 13, 2018    Key Record Dates
Last Update Posted: December 13, 2018
Last Verified: December 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Carlos Ramos, Baylor College of Medicine:
Gene Therapy
CAR T-cells
chimeric antigen receptor
B-Cell Malignancies
CD19

Additional relevant MeSH terms:
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Neoplasms
Neoplasms by Histologic Type
Lymphoma
Lymphoma, Non-Hodgkin
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Leukemia, Lymphoid
Leukemia
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites