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

NCT04083170 | Terminated Phase 2 Results DMC FDA Drug

• 4 other identifiers: RG1004070NCI-2019-05729R34HL14232210304
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 5

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.

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to day 35 post-transplant

Secondary Outcomes (12)

• Incidence of Infusion Toxicities

  Within the first 24 hours after infusion

• Median Number of Days Post-Transplant to Neutrophil Recovery Occurred

  Up to Day 35 post-transplant

• Platelet Engraftment

  35 days post-transplant

• Incidence of Severe (Grades III-IV) Acute Graft Versus Host Disease (GVHD)

  35 days post-transplant

• Incidence of Chronic GVHD

  35 days post-transplant

Study Arms (2)

Regimen A (fludarabine, cyclophosphamide, TBI, dilanubcel)

EXPERIMENTAL

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.

Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: Total-Body Irradiation; Procedure: Umbilical Cord Blood Transplantation; Biological: Dilanubicel

Regimen B (anticancer drugs, TBI, dilanubicel)

EXPERIMENTAL

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.

Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Thiotepa; Radiation: Total-Body Irradiation; Procedure: Umbilical Cord Blood Transplantation; Biological: Dilanubicel

Interventions

Fludarabine DRUG

Given IV

Also known as: 118218, 2-Fluoro-9-beta-arabinofuranosyladenine, 2-Fluorovidarabine, 9-Beta-D-arabinofuranosyl-2-fluoroadenine, Fluradosa

Regimen A (fludarabine, cyclophosphamide, TBI, dilanubcel); Regimen B (anticancer drugs, TBI, dilanubicel)

Cyclophosphamide DRUG

Given IV

Also known as: 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

Regimen A (fludarabine, cyclophosphamide, TBI, dilanubcel); Regimen B (anticancer drugs, TBI, dilanubicel)

Thiotepa DRUG

Given IV

Also known as: STEPA, Tepadina, TESPA, Tespamin, Tespamine, Thiofosfamide, Thio-Tepa, Thiofozil, Thiophosphamide, Thiophosphoramide, Thiotef, Tifosyl, Triethylene thiophosphoramide, Triethylenethiophosphoramide, TSPA, WR 45312

Regimen B (anticancer drugs, TBI, dilanubicel)

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: TBI, TOTAL BODY IRRADIATION, Whole Body Irradiation, Whole-Body Irradiation, SCT_TBI

Regimen A (fludarabine, cyclophosphamide, TBI, dilanubcel); Regimen B (anticancer drugs, TBI, dilanubicel)

Umbilical Cord Blood Transplantation PROCEDURE

Undergo UCBT

Also known as: Cord Blood Transplantation, UCB transplantation

Regimen A (fludarabine, cyclophosphamide, TBI, dilanubcel); Regimen B (anticancer drugs, TBI, dilanubicel)

Dilanubicel BIOLOGICAL

Given IV

Also known as: Allogeneic UCB-derived Hematopoietic Stem and Progenitor Cells NLA101, Allogeneic Umbilical Cord Blood-derived HSPCs NLA101, NLA101

Regimen A (fludarabine, cyclophosphamide, TBI, dilanubcel); Regimen B (anticancer drugs, TBI, dilanubicel)

Eligibility Criteria

• Age: 6 Months - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \>= 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (5)

University of California San Francisco

San Francisco, California, 94143, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Cleveland Cord Blood Center

Cleveland, Ohio, 44128, United States

Location

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Leukemia, Erythroblastic, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Megakaryoblastic, Acute; Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Hematologic Neoplasms; HIV Infections; Myelodysplastic Syndromes; Anemia, Refractory, with Excess of Blasts; Lymphoma, Non-Hodgkin; Anemia, Refractory

Interventions

fludarabine; fludarabine phosphate; Cyclophosphamide; Thiotepa; Whole-Body Irradiation; Cord Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Site; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Anemia; Lymphoma

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Radiotherapy; Therapeutics; Investigative Techniques; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative

Limitations and Caveats

The study was originally intended to be multi-site but ended up only being conducted at the lead site. Due to the rarity of the subject population and the smaller number of enrolling sites, we were not able to reach accrual goals. Once the funding period ended, the study had to be closed to accrual.

Results Point of Contact

• Title: Dr. Filippo Milano
• Organization: Fred Hutchinson Cancer Center

fmilano@fredhutch.org

206.667.5925

Study Officials

• Filippo Milano

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 6, 2019
• First Posted: September 10, 2019
• Study Start: October 6, 2022
• Primary Completion: November 11, 2022
• Study Completion: November 30, 2022
• Last Updated: January 1, 2025
• Results First Posted: January 1, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)