Infusion of Expanded Cord Blood Cells in Addition to Single Cord Blood Transplant in Treating Patients With Acute Leukemia, Chronic Myeloid Leukemia, or Myelodysplastic Syndromes

NCT03399773 | Active Not Recruiting Phase 2 DMC FDA Drug

• 5 other identifiers: 9910NCI-2017-02205P30CA015704P50HL110787RG9218003
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well donor umbilical cord blood transplant with ex-vivo expanded cord blood progenitor cells (dilanubicel) works in treating patients with blood cancer. Before the transplant, patients will receive chemotherapy (fludarabine, cyclophosphamide and in some cases thiotepa) and radiation therapy. Giving chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells.

Conditions

Acute Biphenotypic Leukemia; Acute Lymphoblastic Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Hematopoietic and Lymphoid Cell Neoplasm; Myelodysplastic Syndrome; Myelodysplastic Syndrome With Excess Blasts

Outcome Measures

Primary Outcomes (1)

• Incidence of graft failure

  Primary graft failure/rejection as defined by no neutrophil recovery (regardless of donor chimerism) or autologous recovery (neutrophil recovery but \< 10% donor chimerism in blood and bone marrow \[BM\]).

  Up to day 45 post-transplant

Secondary Outcomes (8)

• Time to neutrophil engraftment

  Up to day 45 post-transplant

• Time to platelet engraftment

  Up to day 100 post-transplant

• Incidence of adverse events

  Up to day 100 post-transplant

• Incidence of non-relapse mortality

  At day 100 post-transplant

• Incidence of non-relapse mortality

  At 1 year post-transplant

Study Arms (1)

Treatment (chemotherapy, TBI, NLA101)

EXPERIMENTAL

Patients receive either regimen A or regimen B. REGIMEN A: Patients (10 through 45 years old) receive fludarabine IV over 30 minutes on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo TBI BID on days -4 to -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0. REGIMEN B: Patients (10 through 65 years old) receive fludarabine IV over 30-60 minutes on days -6 to -3 and IV over 30 minutes on day -2, cyclophosphamide IV on day -6, and thiotepa IV over 2-4 hours on days -5 and -4. Patients undergo TBI QD on days -2 and -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0. All patients undergo bone marrow aspirate and biopsy as clinically indicated during screening and on study. Patients undergo MUGA or ECHO, and CT during screening. Patients also undergo blood sample collection on study.

Biological: Dilanubicel; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Thiotepa; Radiation: Total-Body Irradiation; Procedure: Umbilical Cord Blood Transplantation; Other: Laboratory Biomarker Analysis; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspirate; Procedure: Bone Marrow Biopsy; Procedure: Multigated Acquisition Scan; Procedure: Electrocardiography; Procedure: Computed Tomography

Interventions

Dilanubicel BIOLOGICAL

Given IV

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

Treatment (chemotherapy, TBI, NLA101)

Cyclophosphamide DRUG

Given IV

Also known as: Carloxan, Cicloxal, Mitoxan, Neosar, Revimmune

Treatment (chemotherapy, TBI, NLA101)

Fludarabine DRUG

Given IV

Also known as: fluoroadenine, Fluradosa

Treatment (chemotherapy, TBI, NLA101)

Thiotepa DRUG

Given IV

Also known as: Oncotiotepa, STEPA, Tepadina, TESPA, Tespamine, Thiofosfamide, Thiofozil, Thiophosphoramide, Thiotef, Triethylene Thiophosphoramide

Treatment (chemotherapy, TBI, NLA101)

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: SCT_TBI, Total Body Irradiation, Whole Body Irradiation, Whole-Body Irradiation

Treatment (chemotherapy, TBI, NLA101)

Umbilical Cord Blood Transplantation PROCEDURE

Given IV

Also known as: Cord Blood Transplantation, UCB transplantation

Treatment (chemotherapy, TBI, NLA101)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (chemotherapy, TBI, NLA101)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection

Treatment (chemotherapy, TBI, NLA101)

Bone Marrow Aspirate PROCEDURE

Undergo bone marrow aspirate and biopsy

Also known as: Human Bone Marrow Aspirate

Treatment (chemotherapy, TBI, NLA101)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow aspirate and biopsy

Treatment (chemotherapy, TBI, NLA101)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide ventriculography

Treatment (chemotherapy, TBI, NLA101)

Electrocardiography PROCEDURE

Undergo ECHO

Also known as: ECG, EKG

Treatment (chemotherapy, TBI, NLA101)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT Scan

Treatment (chemotherapy, TBI, NLA101)

Eligibility Criteria

• Age: 10 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients 10 to 65 years old with a hematologic malignancy in need of hematopoietic cell transplant who are \> 30 kg and without a suitable related donor
• Patient must have hematologic malignancy that meets institutional eligibility requirements for cord blood transplant
• Malignancies included are:
• Acute leukemia, including acute myeloid leukemia (AML), biphenotypic acute leukemia or mixed-lineage leukemia, acute lymphoblastic leukemia (ALL); all patients must be in complete response (CR) as defined by \< 5% blasts by morphology/flow cytometry in a representative bone marrow sample with adequate cellularity to assess remission status
• 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% in a representative bone marrow aspirate
• Chronic myeloid leukemia excluding refractory blast crisis; to be eligible in first chronic phase (CP1) patient must have failed or be intolerant to tyrosine kinase inhibitor therapy
• High dose TBI regimen: 10 to =\< 45 years
• Intermediate intensity regimen: 10 to =\< 65 years
• Patients 10 to =\< 45 years: Lansky (\< 16 years old) or Karnofsky (\>= 16 years old) \>= 70 or Eastern Cooperative Oncology Group (ECOG) 0-1
• Patients \> 45 to =\< 65 years: Karnofsky \>= 70 or ECOG 0-1 and non-age adjusted comorbidity index =\< 5
• 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 unless the elevation is thought to be due to Gilbert's disease or hemolysis
• Transaminases must be \< 3 x the upper limit of normal per reference values of treating institution
• Carbon monoxide diffusing capability (DLCO) corrected \>= 60% normal (may not be on supplemental oxygen)

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 unless cleared by infectious disease (ID) consult
• History of human immunodeficiency virus (HIV) infection
• Pregnant or breastfeeding
• Prior allogeneic transplant
• Central nervous system (CNS) leukemic involvement not clearing with intrathecal chemotherapy; diagnostic lumbar puncture is to be performed
• \< 30 kg

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• Nohla Therapeutics, Inc.: collaborator
• National Cancer Institute (NCI): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Leukemia, Biphenotypic, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Hematologic Neoplasms; Myelodysplastic Syndromes; Anemia, Refractory, with Excess of Blasts

Interventions

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

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Site; Anemia, Refractory; Anemia

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

Study Officials

• Filippo Milano

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2017
• First Posted: January 16, 2018
• Study Start: May 10, 2022
• Primary Completion: June 9, 2025
• Study Completion (Estimated): April 2, 2027
• Last Updated: August 26, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)