Cord Blood Transplant With Dilanubicel for the Treatment of HIV Positive Hematologic Cancers

NCT ID: NCT04083170

Last Updated: 2025-01-01

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-06
• Study Completion Date: 2022-11-30

Brief 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.

Detailed Description

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.

Conditions

Acute Erythroid Leukemia; Acute Lymphoblastic Leukemia; Acute Megakaryoblastic Leukemia; Acute Myeloid Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Hematopoietic and Lymphoid Cell Neoplasm; HIV Infection; Myelodysplastic Syndrome; Myelodysplastic Syndrome With Excess Blasts; Non-Hodgkin Lymphoma; Refractory Anemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Fludarabine

Intervention Type: DRUG

Given IV

Cyclophosphamide

Intervention Type: DRUG

Given IV

Total-Body Irradiation

Intervention Type: RADIATION

Undergo TBI

Umbilical Cord Blood Transplantation

Intervention Type: PROCEDURE

Undergo UCBT

Dilanubicel

Intervention Type: BIOLOGICAL

Given IV

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.

Group Type: EXPERIMENTAL

Fludarabine

Intervention Type: DRUG

Given IV

Cyclophosphamide

Intervention Type: DRUG

Given IV

Thiotepa

Intervention Type: DRUG

Given IV

Total-Body Irradiation

Intervention Type: RADIATION

Undergo TBI

Umbilical Cord Blood Transplantation

Intervention Type: PROCEDURE

Undergo UCBT

Dilanubicel

Intervention Type: BIOLOGICAL

Given IV

Interventions

Fludarabine

Given IV

Intervention Type: DRUG

Cyclophosphamide

Given IV

Intervention Type: DRUG

Thiotepa

Given IV

Intervention Type: DRUG

Total-Body Irradiation

Undergo TBI

Intervention Type: RADIATION

Umbilical Cord Blood Transplantation

Undergo UCBT

Intervention Type: PROCEDURE

Dilanubicel

Given IV

Intervention Type: BIOLOGICAL

Other Intervention Names

118218; 2-Fluoro-9-beta-arabinofuranosyladenine; 2-Fluorovidarabine; 9-Beta-D-arabinofuranosyl-2-fluoroadenine; Fluradosa; Carloxan; Ciclofosfamida; Ciclofosfamide; Cicloxal; Clafen; Claphene; CP monohydrate; CTX; CYCLO-cell; Cycloblastin; Cycloblastine; Cyclophospham; Cyclophosphamid monohydrate; Cyclophosphamide Monohydrate; Cyclophosphamidum; Cyclophosphan; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Cytoxan; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; STEPA; Tepadina; TESPA; Tespamin; Tespamine; Thiofosfamide; Thio-Tepa; Thiofozil; Thiophosphamide; Thiophosphoramide; Thiotef; Tifosyl; Triethylene thiophosphoramide; Triethylenethiophosphoramide; TSPA; WR 45312; TBI; TOTAL BODY IRRADIATION; Whole Body Irradiation; Whole-Body Irradiation; SCT_TBI; Cord Blood Transplantation; UCB transplantation; Allogeneic UCB-derived Hematopoietic Stem and Progenitor Cells NLA101; Allogeneic Umbilical Cord Blood-derived HSPCs NLA101; NLA101

Eligibility Criteria

Inclusion Criteria

• >= 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)

Exclusion Criteria

• Uncontrolled viral or bacterial infection at the time of study enrollment
• Active or recent (prior 6 month) invasive fungal infection without infectious disease (ID) consult and approval
• Pregnant or breastfeeding
• Prior myeloablative transplant within the last 6 months
• Extensive prior therapy including > 12 months alkylator therapy or > 6 months alkylator therapy with extensive radiation
• Central nervous system (CNS) leukemic involvement not clearing with intrathecal chemotherapy. Diagnostic lumbar puncture to be performed

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Filippo Milano

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Filippo Milano

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

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

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

NCI-2019-05729

Identifier Type: REGISTRY

Identifier Source: secondary_id

R34HL142322

Identifier Type: NIH

Identifier Source: secondary_id

View Link

10304

Identifier Type: OTHER

Identifier Source: secondary_id

RG1004070

Identifier Type: -

Identifier Source: org_study_id