Multi-virus CTLs Expressing CD19 Chimeric Receptors, CD19 Positive Malignancies Post SCT, MULTIPRAT

Subjects are having a bone marrow or SCT for either a type of cancer of the blood called Leukemia or a cancer of the lymph nodes called non- Hodgkin's Lymphoma. Although a transplant can cure leukemia or lymphoma, some people will relapse. In those who relapse, current treatment cures only a very small percentage. Although giving patients a dose of donor immune cells before relapse can prevent relapse of the leukemia or lymphoma, DLI can also cause a serious complication called graft versus host disease (GVHD). This is a gene transfer research study using special immune cells which are specific for these cancer cells. The body has different ways of fighting infection and disease. This study combines 2 of those ways, antibodies and T cells. T cells (CTLs or cytotoxic T cells) are infection-fighting blood cells that can kill cells, including tumor cells. Antibodies and T cells have been used to treat patients with cancers; they have shown promise, but haven't been strong enough to cure most patients. The antibody used in this study is called anti-CD19. This antibody sticks to leukemia cells because of a substance on the outside of these cells called CD19. For this study, the anti-CD19 antibody has been changed so that instead of floating free in the blood it is now joined to T cells. When an antibody is joined to a T cell in this way it's called a chimeric receptor. In the laboratory, investigators found that T cells that are trained to recognize common viruses can stay in the blood stream for many years. By joining the anti-CD19 antibody to CTLs that recognize viruses, they believe that they will also be able to make a cell that can last a long time in the body, provide protection from viruses, and recognize and kill leukemia. The CTLs which we will join the anti-CD19 antibody to attack 3 viruses (trivirus-specific CTLs), CMV, EBV, and adenovirus. Studies have shown that trivirus-specific CTLs grown from the stem cell donor can be given safely to transplant recipients and can stop these viruses from causing severe infections. These CD19 chimeric receptor trivirus specific T cells are an investigational product not approved by the FDA. The purpose of this study is to find the biggest dose of chimeric T cells that is safe, to assess the side effects, to see how long the T cells last and to evaluate whether this therapy might help prevent infections and relapse in people with CD19+ leukemia or lymphoma having a SCT.

Sex

All

INCLUSION CRITERIA:

1. Any patient regardless of sex or age with CD19+ B-ALL undergoing allogeneic HSCT (Group A)

   OR Any patient regardless of sex or age with CD19+ B-CLL or NHL undergoing allogeneic HSCT (Group B).

   AND

   With minimal residual disease (MRD) or relapse post-HSCT (for the phase I dose escalation)

   OR

   With no evidence of ALL or CLL/NHL post-HSCT (to be included in the expansion cohort
2. Patients with life expectancy greater than or equal to 6 weeks
3. Patients with a Karnofsky/Lansky score greater than or equal to 50
4. Donor HIV negative
5. Patient or parent/guardian capable of providing informed consent
6. Patients with bilirubin 2x normal or less, AST 3x normal or less, creatinine less than or equal to 2x normal for age and Hgb greater than 8.0
7. Pulse oximetry of greater than 90% on room air
8. Sexually active patients must be willing to utilize one of the more effective birth control methods for 6 months after the CTL infusion. The male partner should use a condom.
9. Available allogeneic CD19CAR transduced tri-virus-specific cytotoxic T lymphocytes with greater than or equal to15% expression of CD19CAR determined by flow-cytometry and greater than 10% killing of one or more viral antigen pulsed targets in a cytotoxicity assay at an effector:target ratio of 20:1.\*
10. Patients should have been off other investigational antiviral or antitumor therapy for one month prior to entry in this study.

    * Note: Cell dose is based on total cell numbers and not individual antivirus or antileukemic cell numbers.

EXCLUSION CRITERIA:

1. Severe intercurrent infection
2. Evidence of graft versus host disease \>grade II
3. Pregnant or lactating
4. History of hypersensitivity reactions to murine protein-containing products.
5. Currently taking corticosteroids for therapy of GVHD.

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• DERIVEDCruz CR, Micklethwaite KP, Savoldo B, Ramos CA, Lam S, Ku S, Diouf O, Liu E, Barrett AJ, Ito S, Shpall EJ, Krance RA, Kamble RT, Carrum G, Hosing CM, Gee AP, Mei Z, Grilley BJ, Heslop HE, Rooney CM, Brenner MK, Bollard CM, Dotti G. Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study. Blood. 2013 Oct 24;122(17):2965-73. doi: 10.1182/blood-2013-06-506741. Epub 2013 Sep 12. PMID 24030379