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Acute Erythroid LeukemiaPhase 2NCT04083170

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

A Phase 2 study testing Fludarabine, Cyclophosphamide and Thiotepa in people with Acute Erythroid Leukemia and Acute Lymphoblastic Leukemia, run by Fred Hutchinson Cancer Center at 5 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 6 months to 65 years
What is being tested?
Fludarabine, Cyclophosphamide and Thiotepa
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
5 sitesUnited States
Study dates
6 Oct 2022to 30 Nov 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 6 months to 65 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • >= 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)
Show all 25Show fewer
  • 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)

Who cannot join

  • 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

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • Cleveland Cord Blood Center

    Cleveland, Ohio, 44128

  • University of California San Francisco

    San Francisco, California, 94143

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

Other trials in United States

About this study

Official title: 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

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.

Read the 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.

Being tested
Fludarabine, Cyclophosphamide, Thiotepa, Total-Body Irradiation, Umbilical Cord Blood Transplantation
Medical subject headings
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

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FludarabineDrug

    Also called 118218, 2-Fluoro-9-beta-arabinofuranosyladenine, 2-Fluorovidarabine, 9-Beta-D-arabinofuranosyl-2-fluoroadenine

    Given IV

  • CyclophosphamideDrug

    Also called Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal

    Given IV

  • ThiotepaDrug

    Also called STEPA, Tepadina, TESPA, Tespamin

    Given IV

  • Total-Body IrradiationRadiation

    Also called 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

    Undergo UCBT

  • DilanubicelBiological

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

    Given IV

Study groups in NCT04083170
Study groupRoleWhat they receive
Regimen A (fludarabine, cyclophosphamide, TBI, dilanubcel)ExperimentalPatients 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.
Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: Total-Body Irradiation; Procedure: Umbilical Cord Blood Transplantation; Biological: Dilanubicel
Regimen B (anticancer drugs, TBI, dilanubicel)ExperimentalPatients 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.
Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Thiotepa; Radiation: Total-Body Irradiation; Procedure: Umbilical Cord Blood Transplantation; Biological: Dilanubicel

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to day 35 post-transplant

Secondary outcomes (12)

  1. Incidence of Infusion Toxicities

    Defined as Common Terminology Criteria for Adverse Events version 5.0 grade >= 3 events.

    Measured: Within the first 24 hours after infusion

  2. Median Number of Days Post-Transplant to Neutrophil Recovery Occurred

    Neutrophil recovery is defined as the first day of 2 consecutive days of absolute neutrophil count >= 500 after the first post-cord blood transplant nadir. This outcome was originally intended to be assessed for up to 45 days post-transplant, but was only able to be assessed through 35 days post-transplant.

    Measured: Up to Day 35 post-transplant

  3. Platelet Engraftment

    Will be defined as the first day of a platelet count > 20,000/ul with subsequent transfusions for 7 days. This outcome was originally intended to be assessed for up to 2 years post-transplant, but was only able to be assessed through 35 days post-transplant.

    Measured: 35 days post-transplant

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

    Will be defined by the 2014 National Institutes of Health (NIH) criteria. This outcome was originally intended to be assessed for up to 2 years post-transplant, but was only able to be assessed through 35 days post-transplant.

    Measured: 35 days post-transplant

  5. Incidence of Chronic GVHD

    Will be defined by the 2014 NIH criteria. This outcome was originally intended to be assessed for up to 2 years post-transplant, but was only able to be assessed through 35 days post-transplant.

    Measured: 35 days post-transplant

  6. Incidence of Non-relapse Mortality

    Will be defined as death without a prior relapse. This outcome was originally intended to be assessed for up to 180 days post-transplant, but was only able to be assessed through 35 days post-transplant.

    Measured: 35 days post-transplant

  7. Human Immunodeficiency Virus (HIV) Plasma Viral Load

    Assess CCR5Δ32 cord blood stem cell engraftment and its effect on biomarkers of HIV-1 infection, including plasma viral load and replication-competent reservoirs, as well as in gut and other sites (if tissue samples are available). This outcome was originally intended to be assessed weekly for up to 2 years post-transplant, but was only able to be assessed through 35 days post-transplant.

    Measured: Baseline and weekly to 35 days post-transplant

  8. Immune Homeostasis

    Concentration of immunity cells per microliters after transplant

    Measured: Up to 2 years

  9. Immune Reconstitution

    Concentration of immunity cells per microliters after transplant

    Measured: Up to 2 years

  10. Change in HIV-1 Induced Inflammatory Immune Responses

    HIV viral load by PCR (copies per milliliter; mL)

    Measured: Up to 2 years

  11. HIV Rebound Following Antiretroviral Therapy (ART) Cessation

    Count of participants with HIV rebound, measured by HIV viral load by PCR (copies per milliliter; mL)

    Measured: Up to 2 years

  12. Viral Kinetics Following ART Cessation

    HIV viral load by PCR (copies per milliliter; mL)

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Sep 2019
  2. Study start6 Oct 2022
  3. Primary completion11 Nov 2022
  4. Study completion30 Nov 2022

Why it stopped: The federal funding period ended. The study was originally intended to be multi-site but was only conducted at the lead site. Due to the rarity of the subject population \& smaller # of enrolling sites, we were not able to reach accrual goals.

Resources

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04083170
Sponsor's protocol ID
RG1004070
Other IDs
NCI-2019-05729, R34HL142322, 10304
Status last verified
Dec 2024
First submitted
6 Sep 2019
Last updated
1 Jan 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Fludarabine, Cyclophosphamide and Thiotepa in people with Acute Erythroid Leukemia and Acute Lymphoblastic Leukemia, run by Fred Hutchinson Cancer Center at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 1 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Primary Graft Failure Rejection (time frame: Up to day 35 post-transplant). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04083170.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jan 2025.

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