This phase II trial studies the side effects of a cord blood transplant using dilanubicel and to see how well it works in treating patients with human immunodeficiency virus (HIV) positive hematologic (blood) cancers. After a cord blood transplant, the immune cells, including white blood cells, can take a while to recover, putting the patient at increased risk of infection. Dilanubicel consists of blood stem cells that help to produce mature blood cells, including immune cells. Drugs used in chemotherapy, such as fludarabine, cyclophosphamide, and thiotepa, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Total body irradiation is a type of whole-body radiation. Giving chemotherapy and total-body irradiation before a cord blood transplant with dilanubicel may help to kill any cancer cells that are in the body and make room in the patient’s bone marrow for new stem cells to grow and reduce the risk of infection.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT04083170.
PRIMARY OBJECTIVE:
I. To show that single unit cord blood transplantation characterized with the CCR5delta32 mutation augmented with a single dose of dilanubicel is not associated with an excess of graft failure.
SECONDARY OBJECTIVES:
I. Examine the safety and toxicity of infusing dilanubicel.
II. Evaluate neutrophil and platelet engraftment.
III. Determine incidence of acute graft versus host disease (GVHD) at day 100 and chronic GVHD at 1 year.
IV. Determine non-relapse mortality at day 100 and 180.
V. Assess CCR5delta32 cord blood stem cell engraftment and its effect on biomarkers of HIV-1 infection, including plasma viral load and replication-competent reservoirs, as well as in gut and other sites (if tissue samples are available).
VI. Examine immune homeostasis and reconstitution after transplantation with CCR5delta32 cord blood stem cells.
VII. Assess the changes in HIV-1 induced inflammatory effects (systemic inflammation and activation of innate and adaptive immune cells) and HIV-1 specific immune responses (antibody and T cell responses) pre- and post- CCR5delta32 cord blood stem cell transplantation in all cohorts.
VIII. Evaluate time to HIV rebound and viral kinetics following antiretroviral therapy (ART) cessation.
EXPLORATORY OBJECTIVES:
I. Evaluate in vivo persistence of dilanubicel.
II. Determine duration of initial hospitalization from day 0 post-transplant.
III. Determine overall survival at 1 year.
IV. Obtain preliminary data on the incidence of infections/viral reactivation from the start of conditioning to 100 days post-transplant and then at 6 months, 1 year and 2 years post-transplant as possible.
OUTLINE: Patients are assigned to 1 of 2 regimens.
REGIMEN A: Patients receive fludarabine intravenously (IV) over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6, and undergo total body irradiation (TBI) twice daily (BID) on days -4 to -1. Patients then undergo umbilical cord blood transplant on day 0. Between 4-24 hours after transplant completion, patients receive dilanubicel IV over 5-10 minutes in the absence of disease progression or unacceptable toxicity.
REGIMEN B: Patients receive fludarabine IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo TBI once daily (QD) on days -2 to -1. Patients then undergo umbilical cord blood transplant on day 0. Between 4-24 hours after transplant completion, patients receive dilanubicel IV over 5-10 minutes in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 28, 80, and 180 days, and then at 1 and 2 years.
Lead OrganizationFred Hutch/University of Washington/Seattle Children's Cancer Consortium
Principal InvestigatorFilippo Milano