Administration of Anti-CD19-chimeric-antigen-receptor-transduced T Cells From the Original Transp… (NCT01087294) | Clinical Trial Compass
CompletedPhase 1
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
United States85 participantsStarted 2010-08-04
Plain-language summary
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.
Who can participate
Age range18 Years – 75 Years
SexALL
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Inclusion criteria
✓. Recipients (patients with B-cell malignancy) must have received an HLA-identical or 9/10 matched sibling allogeneic hematopoietic stem cell transplant, or a greater than or equal to 9/10-matched unrelated donor (URD) alloHSCT for any CD19+ B-cell malignancy. Haploidentical donors will not be used in this protocol. Patients with any CD19+ B-cell malignancy that is persistent or relapsed after all of the following interventions are eligible:
✓. Donor engraftment after alloHSCT (\>50% donor chimerism of the blood T cells or whole blood leukocytes or whole bone marrow).
✓. A trial of withdrawal of immunosuppressive therapy.
✓. CD19 expression must be detected on the majority of the malignant cells by immunohistochemistry or by flow cytometry in the Laboratory of Pathology, CCR, NCI, NIH. Definition of which cells are malignant must be determined for each patient by the Laboratory of Pathology using techniques to demonstrate monoclonality such as kappa/lambda restriction (other techniques can be used to determine monoclonality at the discretion of the Laboratory of Pathology). The choice of whether to use flow cytometry or immuohistochemistry will be determined by what is the most easily available tissue sample in each patient. Immunohistochemistry will be used for lymph node biopsies and bone marrow biopsies. Flow cytometry will be used for peripheral blood, fine needle aspirate, and bone marrow aspirate samples.
. Performance status: ECOG less than or equal to 2
✓. Either no evidence of GVHD or minimal clinical evidence of acute GVHD and chronic GVHD while off of systemic immunosuppressive therapy for at least 28 days. Minimal clinical evidence of acute GVHD is defined as grade 0 to I acute GVHD. Minimal evidence of chronic GVHD is defined as chronic GVHD with no organ site with a score exceeding 1, except for the skin, for which a score of 1 or 2 will be allowable (as defined by the 2005 NIH consensus project) or no chronic GVHD. Subjects with disease that is controlled to stage I acute GVHD or chronic GVHD meeting the above criteria with local therapy only, e.g., topical cutaneous steroids, will be eligible for enrollment.
✓. Ability to give informed consent.
Exclusion criteria
✕. 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).