Administration of Anti-CD19-chimeric-antigen-receptor-transduced T Cells From the Original Transplant Donor to Patients With Recurrent or Persistent B-cell Malignancies After Allogeneic Stem Cell Transplantation

Completed · Phase 1

Conditions studied: Leukemia, B-cell, Lymphoma, Hodgkins, Lymphoma, Non-hodgkins, Lymphoma, B-Cell

In brief

Background: * Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a procedure that transplants bone marrow cells (stem cells) from a matching donor into a recipient in order to allow the donor stem cells to produce cells that will attack the recipient s cancer cells. AlloHSCT is performed when chemotherapy, immunotherapy, or radiation therapy do not adequately control cancer growth. However, cancers that are not controlled by alloHSCT frequently become resistant to other standard treatment options. * The outcomes of alloHSCT might be improved if certain kinds of white blood cells (T cells) could be manipulated so that they generate a more potent effect against the cancer cells. This effect can be augmented by genetically engineering donor T cells to specifically recognize cancerous cells in order to attack them. For this purpose, researchers are studying a specific kind of genetically engineered T cell known as the anti-CD19-CAR-transduced T cell. More research is needed to determine if this T cell will be an effective treatment for certain kinds of B cell cancer (such as non-Hodgkin s lymphoma and chronic lymphocytic leukemia) that has not been controlled with alloHSCT. Objectives: \- To assess the safety and effectiveness of administering allogeneic anti-CD19-CAR-transduced T cells to patients with B-cell cancer that has not responded to alloHSCT. Eligibility: * Individuals between 18 and 75 years of age who have received allogeneic hematopoietic stem cell transplantation for a B cell cancer, but whose cancer has either not responded to or recurred after the transplant. * Recipients must have the same stem cell donor from their previous procedure. Design: * Before the start of the study, all participants will be screened with a medical history and blood tests. Recipients will have tumor imaging scans, additional blood tests, and other tests as directed by the study doctors. * Donor participants will undergo apheresis to provide white blood cells for researchers to use in the treatment. * Recipients will have dose escalation to determine the most effective yet safe dose of anti-CD19 T cells. There will be six dose levels of anti-CD19 T cells. The first patients enrolled will have the smallest dose, and the dose will be increased when a level has been determined to be safe. . * Recipients will be hospitalized for at least 9 days after receiving the cell infusion, and will need to come to clinic for follow-up visits 2, 4, 8, and 12 weeks after the infusion. * Additional scans and frequent blood tests will be required for the first 3 months after the infusion, followed by less frequent visits over time. * Recipients will be followed for a maximum of 15 years after receiving the infusion.

Key facts

Study ID

NCT01087294

Run by

National Cancer Institute (NCI)

People needed

85

Starts

2010-08-04

Expected to finish

2024-04-02

Last updated by the study team

2026-08-07

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• Exclusion Criteria: Recipients
• Active infection that is not responding to antimicrobial therapy.
• Sero positive for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune -competence and thus are less responsive to the experimental treatment and more susceptible to its toxicities.)
• Sero positive for hepatitis B antigen, positive hepatitis B tests can be further evaluated by confirmatory tests (HBV DNA), and if confirmatory tests are negative, the patient can be enrolled.
• Sero positive for hepatitis C antibody unless antigen negative. If hepatitis C antibody test is positive, then patients must be tested for the presence of RNA by RT-PCR and be HCV RNA negative.
• Active psychiatric disorder which may compromise compliance with the treatment protocol, or which does not allow for appropriate informed consent (as determined by Principal Investigator and/or his designee).
• Pregnant or lactating. The effects of the immunosuppressive medications that could be required to treat GHVD are likely to be harmful to a fetus. The effects upon breast milk are also unknown and may be harmful to an infant.
• Serum total bilirubin > 2.5 mg/dl, serum ALT and AST values greater than or equal to 2.5 times the upper limit of normal based on age-specific normal values. If the abnormal liver function is attributable to liver involvement by malignancy, patients may be eligible with serum total bilirubin up to 5.0 mg/dl, and serum ALT and AST values up to 5.0 times the upper limit of normal, provided the patient has no evidence of impending hepatic failure (encephalopathy or prothrombin time >2 time the upper limit of normal).
• Serum creatinine greater than 1.6 mg/dL
• Absolute neutrophil count of less than 1000 cells/ml unless low neutrophil count is thought to be due to malignancy in the bone marrow and malignancy is documented in the bone marrow.
• Active cerebrospinal fluid involvement with malignancy or brain metastasis.
• Platelet count less than 30,000/ml unless low platelet count is thought to be due to malignancy in the bone marrow and malignancy is documented in the bone marrow.
• Hemoglobin less than 8.0 g/dL.
• Receiving systemic corticosteroids including prednisone, dexamethasone or any other corticosteroid at doses of higher than 5 mg/day of prednisone within 28 days prior to anti-CD19-CAR-transduced T cell administration. Corticosteroid creams, ointments, and eye drops are allowed.
• Blood blast percentage higher than 5%.
• Exclusion Criteria: Donors
• History of psychiatric disorder which may compromise compliance with this protocol or which does not allow for appropriate informed consent.
• History of hypertension that is not controlled by medication, stroke, or severe heart disease (donors with symptomatic angina will be excluded). Donors with a history of coronary artery bypass grafting or angioplasty who are symptom free will receive a cardiology evaluation and be considered on a case-by-case basis.
• Donors must not be pregnant.
• Anemia (Hb < 11 gm/dl) or thrombocytopenia (platelets < 100,000 per ml). However, potential donors with Hb levels < 11 gm/dl that is due to iron deficiency will be eligible as long as the donor is initiated on iron replacement therapy. The NIH Clinical Center, Department of Transfusion Medicine/NMDP physicians will determine the appropriateness of individuals as donors.

Where it is running

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States
• National Marrow Donor Program — Minneapolis, Minnesota, United States

Full record on ClinicalTrials.gov

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