Acute Biphenotypic LeukemiaPhase 2NCT03399773
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
A Phase 2 study testing Dilanubicel, Cyclophosphamide and Fludarabine in people with Acute Biphenotypic Leukemia and Acute Lymphoblastic Leukemia, run by Fred Hutchinson Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 10 to 65 years
- Conditions the study is for
- Acute Biphenotypic Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, BCR-ABL1 Positive
- What is being tested?
- Dilanubicel, Cyclophosphamide and Fludarabine
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- 10 May 2022to 2 Apr 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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)
- For pediatric patients unable to perform pulmonary function tests, O2 saturation > 92% on room air
- Left ventricular ejection fraction >= 50% OR
- Shortening fraction > 26%
- Ability of participant or legally authorized representative to understand and the willingness to sign a written informed consent form
- DONOR: Minimum requirement: The cord blood (CB) unit must be matched at a minimum at 4/6 HLA-A, B antigens and DRB1 allele with the recipient; therefore, 0-2 mismatches at the A or B or DRB1 loci based on intermediate resolution at HLA-A, B and high resolution allele level typing at HLA- DRB1 are allowed
- DONOR: Institutional guidelines for HLA-match may be followed as long as the minimum criteria for HLA-matching as above are met
- DONOR: The CB unit selected for transplant must have a MINIMUM of 2.5 x 10^7 TNC/kg
- DONOR: The minimum recommended CD34/kg cell dose is 1.7 x 10^5 CD34/kg
- DONOR: A backup unit must be identified and reserved prior to the start of the treatment plan for possible infusion in the unlikely event of poor post-thaw viability of the primary CB unit. A suitable back up unit will be considered, as follows:
- Must be matched at a minimum at 4/6 HLA-A, B, DRBl loci with the recipient. Therefore 0-2 mismatches at the A or B or DRBl loci based on intermediate resolution A, B antigen and DRBl allele typing for determination of HLA-match is allowed (Fred Hutch Protocol 2010).
- Must contain a MINIMUM of 1.5 x 10^7 TNC/kg to ensure the same requirement we use for a standard double CBT per CB selection guideline (Fred Hutch Protocol 2010).
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109
About this study
Official title: Pilot Study: Infusion of Off-the-Shelf Ex Vivo Expanded Cryopreserved Progenitor Cells (Dilanubicel) in the Setting of Single Cord Blood Transplantation for Patients With Hematologic Malignancies
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.
Read the detailed description
OUTLINE:
Patients receive either regimen A or regimen B.
REGIMEN A: Patients (10 through 45 years old) receive fludarabine intravenously (IV) over 30 minutes on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo total body irradiation (TBI) twice daily (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 once daily (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 multigated acquisition scan (MUGA) or echocardiography (ECHO), and computed tomography (CT) during screening. Patients also undergo blood sample collection on study.
After completion of study treatment, patients are followed up at 180 days, 1 year, and 2 years.
- 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
- Being tested
- Dilanubicel, Cyclophosphamide, Fludarabine, Thiotepa, Total-Body Irradiation
- Medical subject headings
- Leukemia, Biphenotypic, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Hematologic Neoplasms, Myelodysplastic Syndromes, Anemia, Refractory, with Excess of Blasts
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DilanubicelBiological
Also called Allogeneic UCB-derived Hematopoietic Stem and Progenitor Cells NLA101, NLA101, Allogeneic Umbilical Cord Blood-derived HSPCs NLA101
Given IV
CyclophosphamideDrug
Also called Carloxan, Cicloxal, Mitoxan, Neosar
Given IV
FludarabineDrug
Also called fluoroadenine, Fluradosa
Given IV
ThiotepaDrug
Also called Oncotiotepa, STEPA, Tepadina, TESPA
Given IV
Total-Body IrradiationRadiation
Also called SCT_TBI, Total Body Irradiation, Whole Body Irradiation, Whole-Body Irradiation
Undergo TBI
Umbilical Cord Blood TransplantationProcedure or surgery
Also called Cord Blood Transplantation, UCB transplantation
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection
Undergo blood sample collection
Bone Marrow AspirateProcedure or surgery
Also called Human Bone Marrow Aspirate
Undergo bone marrow aspirate and biopsy
Bone Marrow BiopsyProcedure or surgery
Undergo bone marrow aspirate and biopsy
Multigated Acquisition ScanProcedure or surgery
Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, MUGA Scan
Undergo MUGA
ElectrocardiographyProcedure or surgery
Also called ECG, EKG
Undergo ECHO
Computed TomographyProcedure or surgery
Also called CAT Scan
Undergo CT
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With 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]).
Measured: Up to day 45 post-transplant
Secondary outcomes (8)
Number of Participants Who Experienced Grade ≥3 Adverse Events Related to Study Product
Adverse events (AEs) were graded using the CTCAE v5.0. This outcome measured the number of participants who experienced at least one grade ≥ 3 adverse event considered related to the study product during the period of start of infusion of the study product (Day 0) until 100 days following transplant. An AE is considered related to the study product based on investigator assessment if it was assessed as definitely, probably, or possibly related; unrelated if it is assessed as unlikely related or unrelated.
AE severity grade, seriousness, and relatedness were evaluated independently; therefore, grade ≥3 events were not necessarily serious adverse events (SAEs). Reporting of grade ≥3 AEs and all-grade SAEs is provided in the Adverse Events module.
Dose-limiting toxicities (DLTs) were predefined.
Measured: From study product infusion start through day 100 post-transplant
Time to Neutrophil Engraftment
The day of neutrophil recovery will be the 1st day of 2 consecutive days of absolute neutrophil count at or above 500 after the 1st post-cord blood transplant nadir.
Measured: Up to day 45 post-transplant
Time to Platelet Engraftment
Measured by the number of participants with a platelet count > 20,000/ul without subsequent transfusions for 7 days. Participants who did not reach platelet engraftment by day 100 post-transplant were censored at day 100.
Measured: Up to day 100 post-transplant
Number of Participants With Acute Graft Versus Host Disease (aGVHD), by Grade
The presence of aGVHD was assessed using the Acute GVHD Grading Scale and represented as overall grade I-IV, with higher grade indicating worse outcomes. Grade I aGVHD is defined as skin stage 1-2 and stage 0 for both GI and liver. Grade II is stage 3 skin, stage 1 GI, or stage 1 liver. Grade III is stage 4 skin or stage 2-4 GI or stage 2-4 liver, without GVHD as a major contributing cause of death. Grade IV is stage 4 skin or stage 2-4 GI or stage 2-4 liver, with GVHD as a major contributing cause of death.
Measured: At day 100 post-transplant
Number of Participants With Chronic Graft Versus Host Disease (cGVHD), by Severity
The presence of cGVHD was assessed using the Chronic GVHD Grading Scale, with higher severity indicating worse outcomes. Incidence of moderate or severe cGVHD were considered clinically significant. Mild cGVHD is defined as limited organ involvement with minimal functional impairment, typically affecting 1-2 organs/sites with no major impact on daily activities. Moderate cGVHD is indicated by more extensive organ involvement and/or clinically significant functional impairment, but without major disability. Severe cGVHD is defined as major organ involvement with substantial functional impairment or disability, often requiring intensive systemic therapy. Abnormalities that could indicate cGVHD are reviewed for the following organ systems: skin, nails, hair, mouth, eyes, vagina/vulva (for female patients), liver, lung, GI, fasciitis, serositis, muscle, skeletal.
Measured: 1 year post-transplant
Number of Participants With Chronic Graft Versus Host Disease (cGVHD), by Severity
The presence of cGVHD was assessed using the Chronic GVHD Grading Scale, with higher severity indicating worse outcomes. Incidence of moderate or severe cGVHD were considered clinically significant. Mild cGVHD is defined as limited organ involvement with minimal functional impairment, typically affecting 1-2 organs/sites with no major impact on daily activities. Moderate cGVHD is indicated by more extensive organ involvement and/or clinically significant functional impairment, but without major disability. Severe cGVHD is defined as major organ involvement with substantial functional impairment or disability, often requiring intensive systemic therapy. Abnormalities that could indicate cGVHD are reviewed for the following organ systems: skin, nails, hair, mouth, eyes, vagina/vulva (for female patients), liver, lung, GI, fasciitis, serositis, muscle, skeletal.
Measured: Up to 2 years post-transplant
Number of Participants Who Experienced Non-relapse Mortality
Non-relapse mortality (NRM) is defined as death without a prior relapse.
Measured: At day 100 post-transplant
Number of Participants Who Experienced Non-relapse Mortality
Non-relapse mortality (NRM) is defined as death without a prior relapse.
Measured: At day 180 post-transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2018
- Study start10 May 2022
- Primary completion9 Jun 2025
- Study completion2 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Biphenotypic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fred Hutchinson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Nohla Therapeutics, Inc., National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Filippo Milano, Fred Hutchinson Cancer Center
- Investigators
- Filippo Milano, Principal investigator, Fred Hutch/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03399773
- Sponsor's protocol ID
- 9910
- Other IDs
- NCI-2017-02205, 9910, P30CA015704, P50HL110787, RG9218003
- Status last verified
- Jun 2026
- First submitted
- 15 Dec 2017
- Last updated
- 10 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No