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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1
Given IV
Given IV
Given IV
Undergo TBI
Undergo UCBT
Given IV
University of California San Francisco
San Francisco, California, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Case Western Reserve University
Cleveland, Ohio, United States
Cleveland Cord Blood Center
Cleveland, Ohio, United States
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Primary Graft Failure Rejection
Will be defined by no neutrophil recovery by day 45 (regardless of donor chimerism) or autologous recovery (neutrophil recovery but \< 10% donor chimerism in blood and bone marrow) by day 36. This outcome was originally intended to be assessed for per the aforementioned definitions, but was only able to be assessed through 35 days post-transplant.
Time frame: Up to day 35 post-transplant
Incidence of Infusion Toxicities
Defined as Common Terminology Criteria for Adverse Events version 5.0 grade \>= 3 events.
Time frame: Within the first 24 hours after infusion
Median Number of Days Post-Transplant to Neutrophil Recovery Occurred
Neutrophil recovery is defined as the first day of 2 consecutive days of absolute neutrophil count \>= 500 after the first post-cord blood transplant nadir. This outcome was originally intended to be assessed for up to 45 days post-transplant, but was only able to be assessed through 35 days post-transplant.
Time frame: Up to Day 35 post-transplant
Platelet Engraftment
Will be defined as the first day of a platelet count \> 20,000/ul with subsequent transfusions for 7 days. This outcome was originally intended to be assessed for up to 2 years post-transplant, but was only able to be assessed through 35 days post-transplant.
Time frame: 35 days post-transplant
Incidence of Severe (Grades III-IV) Acute Graft Versus Host Disease (GVHD)
Will be defined by the 2014 National Institutes of Health (NIH) criteria. This outcome was originally intended to be assessed for up to 2 years post-transplant, but was only able to be assessed through 35 days post-transplant.
Time frame: 35 days post-transplant
Incidence of Chronic GVHD
Will be defined by the 2014 NIH criteria. This outcome was originally intended to be assessed for up to 2 years post-transplant, but was only able to be assessed through 35 days post-transplant.
Time frame: 35 days post-transplant
Incidence of Non-relapse Mortality
Will be defined as death without a prior relapse. This outcome was originally intended to be assessed for up to 180 days post-transplant, but was only able to be assessed through 35 days post-transplant.
Time frame: 35 days post-transplant
Human Immunodeficiency Virus (HIV) Plasma Viral Load
Assess CCR5Δ32 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). This outcome was originally intended to be assessed weekly for up to 2 years post-transplant, but was only able to be assessed through 35 days post-transplant.
Time frame: Baseline and weekly to 35 days post-transplant
Immune Homeostasis
Concentration of immunity cells per microliters after transplant
Time frame: Up to 2 years
Immune Reconstitution
Concentration of immunity cells per microliters after transplant
Time frame: Up to 2 years
Change in HIV-1 Induced Inflammatory Immune Responses
HIV viral load by PCR (copies per milliliter; mL)
Time frame: Up to 2 years
HIV Rebound Following Antiretroviral Therapy (ART) Cessation
Count of participants with HIV rebound, measured by HIV viral load by PCR (copies per milliliter; mL)
Time frame: Up to 2 years
Viral Kinetics Following ART Cessation
HIV viral load by PCR (copies per milliliter; mL)
Time frame: Up to 2 years
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