Infusion of Off-the-Shelf Ex Vivo Expanded Cryopreserved Progenitor Cells to Facilitate the Engraftment of a Single CCR5Δ32 Homozygous or Heterozygous Cord Blood Unit in Patients With HIV and Hematological Malignancies

Who is this study for? Patients with Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia
Status: Recruiting
Location: See all (6) locations...
Intervention Type: Drug, Radiation, Procedure, Biological
Study Type: Interventional
Study Phase: Phase 2
SUMMARY

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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 6 months
Maximum Age: 65
Healthy Volunteers: No
View:

• >= 6 months to =< 65 years

• Treatment with combination antiretroviral therapy (cART) for at least 1 month before enrollment

• Viral load < 5000 copies/ml plasma on cART

• Disease criteria

• Acute myeloid leukemia

• High risk in first complete remission (CR1), >= 2 cycles to obtain complete remission (CR), erythroblastic or megakaryocytic leukemia; >= in second complete remission (CR2)

• All patients must be in CR as defined by hematologic recovery and < 5% blasts by morphology within the bone marrow and a cellularity of >= 15%

• Patients for whom adequate marrow/biopsy specimens cannot be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry, recovery of peripheral blood counts with no circulating blasts, and/or normal cytogenetics (if applicable) may still be eligible. Specimen for morphologic assessment, including possible repeat procedures will be obtained (as possible). These patients must be discussed with the lead principal investigator, Filippo Milano prior to enrollment

• Acute lymphoblastic leukemia

• High risk CR1 (for example, but not limited to: t(9;22), t(1;19), t(4;11) or other mixed-lineage leukemia [MLL] rearrangements, hypodiploid); greater than 1 cycle to obtain CR; >= CR2

• All patients must be in CR as defined by hematologic recovery and < 5% blasts by morphology within the bone marrow and a cellularity of >= 15%

• Patients in which adequate marrow/biopsy specimens cannot be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry, recovery of peripheral blood counts with no circulating blasts, and/or normal cytogenetics (if applicable) may still be eligible. Specimen for morphologic assessment, including possible repeat procedures will be obtained (as possible). These patients must be discussed with the lead principal investigator, Filippo Milano prior to enrollment

• Chronic myelogenous leukemia excluding refractory blast crisis. To be eligible in first chronic phase (CP1) patient must have failed or be intolerant to imatinib mesylate

• Myelodysplasia (MDS) International Prognostic Scoring System (IPSS) intermediate (Int)-2 or high risk (i.e., refractory anemia with excess blasts [RAEB], refractory anemia with excess blasts in transformation [RAEBt]) or refractory anemia with severe pancytopenia or high-risk cytogenetics. Blasts must be < 10% by a representative bone marrow aspirate morphology

• Other hematologic malignancy such as non-Hodgkin lymphomas. Fred Hutch site: These patients must be presented at Patient Care Conference (PCC) prior to enrollment, given potential competing eligibility on auto-transplant protocols. Participating centers: These patients must be discussed with the lead principal investigator, Filippo Milano prior to enrollment

• Karnofsky (>= 16 years old) >= 70%

• Lansky (< 16 years old) >= 50%

• Adults: Calculated creatinine clearance must be > 60 mL and serum creatinine =< 2 mg/dL

• Children (< 18 years old): Calculated creatinine clearance must be > 60 mL/min

• Total serum bilirubin must be < 3 mg/dL

• Transaminases must be < 3 x the upper limit of normal

• Diffusion capacity of the lung for carbon monoxide (DLCO) corrected > 50% normal or for pediatric patients in whom DLCO cannot be measured has adequate pulmonary function

• Left ventricular ejection fraction > 45% OR

• Shortening fraction > 26%

• Ability to understand and the willingness to sign a written informed consent document (adult subject or parent/legal guardian of minor subject)

Locations
United States
California
University of California San Francisco
Not yet recruiting
San Francisco
Washington, D.c.
Children's National Medical Center
Not yet recruiting
Washington
New York
Memorial Sloan Kettering Cancer Center
Withdrawn
New York
Ohio
Case Western Reserve University
Not yet recruiting
Cleveland
Cleveland Cord Blood Center
Recruiting
Cleveland
Washington
Fred Hutch/University of Washington Cancer Consortium
Recruiting
Seattle
Contact Information
Primary
Filippo Milano
fmilano@fredhutch.org
206.667.5925
Time Frame
Start Date: October 6, 2022
Estimated Completion Date: December 31, 2025
Participants
Target number of participants: 10
Treatments
Experimental: Regimen A (fludarabine, cyclophosphamide, TBI, dilanubcel)
Patients receive fludarabine IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6, and undergo TBI 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.
Experimental: Regimen B (anticancer drugs, TBI, dilanubicel)
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 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.
Authors
Juliet Barker, Filippo Milano, Mary Laughlin, Kirsten Boughan, Timothy Henrich, Blachy Saldana
Sponsors
Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
Leads: Fred Hutchinson Cancer Center

This content was sourced from clinicaltrials.gov

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