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

Primary Purpose

Acute Erythroid Leukemia, Acute Lymphoblastic Leukemia, Acute Megakaryoblastic Leukemia

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Fludarabine
Cyclophosphamide
Thiotepa
Total-Body Irradiation
Umbilical Cord Blood Transplantation
Dilanubicel
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Erythroid Leukemia

Eligibility Criteria

6 Months - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of California San Francisco
  • Children's National Medical Center
  • Memorial Sloan Kettering Cancer Center
  • Case Western Reserve University
  • Cleveland Cord Blood CenterRecruiting
  • Fred Hutch/University of Washington Cancer ConsortiumRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Regimen A (fludarabine, cyclophosphamide, TBI, dilanubcel)

Regimen B (anticancer drugs, TBI, dilanubicel)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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 45.

Secondary Outcome Measures

Incidence of infusion toxicities
Defined as Common Terminology Criteria for Adverse Events version 5.0 grade >= 3 events.
Neutrophil recovery
Will be defined as the first day of 2 consecutive days of absolute neutrophil count >= 500 after the first post-cord blood transplant nadir.
Platelet engraftment
Will be defined as the first day of a platelet count > 20,000/ul with subsequent transfusions for 7 days.
Severe (grades III-IV) acute graft versus host disease (GVHD)
Will be defined by the 2014 National Institutes of Health (NIH) criteria.
Chronic GVHD
Will be defined by the 2014 NIH criteria.
Non-relapse mortality
Will be defined as death without a prior relapse.
Human immunodeficiency virus (HIV) plasma viral load
Immune homeostasis
Concentration of immunity cells per microliters after transplant
Immune reconstitution
Concentration of immunity cells per microliters after transplant
Change in HIV-1 induced inflammatory immune responses
HIV viral load by PCR (copies per milliliter; mL)
HIV rebound following antiretroviral therapy (ART) cessation
HIV viral load by PCR (copies per milliliter; mL)
Viral kinetics following ART cessation
HIV viral load by PCR (copies per milliliter; mL)

Full Information

First Posted
September 6, 2019
Last Updated
May 24, 2023
Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT04083170
Brief Title
Cord Blood Transplant With Dilanubicel for the Treatment of HIV Positive Hematologic Cancers
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 6, 2022 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Regimen A (fludarabine, cyclophosphamide, TBI, dilanubcel)
Arm Type
Experimental
Arm Description
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.
Arm Title
Regimen B (anticancer drugs, TBI, dilanubicel)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
118218, 2-Fluoro-9-beta-arabinofuranosyladenine, 2-Fluorovidarabine, 9-Beta-D-arabinofuranosyl-2-fluoroadenine, Fluradosa
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
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
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Thiotepa
Other Intervention Name(s)
STEPA, Tepadina, TESPA, Tespamin, Tespamine, Thiofosfamide, Thio-Tepa, Thiofozil, Thiophosphamide, Thiophosphoramide, Thiotef, Tifosyl, Triethylene thiophosphoramide, Triethylenethiophosphoramide, TSPA, WR 45312
Intervention Description
Given IV
Intervention Type
Radiation
Intervention Name(s)
Total-Body Irradiation
Other Intervention Name(s)
TBI, TOTAL BODY IRRADIATION, Whole Body Irradiation, Whole-Body Irradiation, SCT_TBI
Intervention Description
Undergo TBI
Intervention Type
Procedure
Intervention Name(s)
Umbilical Cord Blood Transplantation
Other Intervention Name(s)
Cord Blood Transplantation, UCB transplantation
Intervention Description
Undergo UCBT
Intervention Type
Biological
Intervention Name(s)
Dilanubicel
Other Intervention Name(s)
Allogeneic UCB-derived Hematopoietic Stem and Progenitor Cells NLA101, Allogeneic Umbilical Cord Blood-derived HSPCs NLA101, NLA101
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Primary graft failure rejection
Description
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 45.
Time Frame
Up to day 45
Secondary Outcome Measure Information:
Title
Incidence of infusion toxicities
Description
Defined as Common Terminology Criteria for Adverse Events version 5.0 grade >= 3 events.
Time Frame
Within the first 24 hours after infusion
Title
Neutrophil recovery
Description
Will be defined as the first day of 2 consecutive days of absolute neutrophil count >= 500 after the first post-cord blood transplant nadir.
Time Frame
Up to 2 years
Title
Platelet engraftment
Description
Will be defined as the first day of a platelet count > 20,000/ul with subsequent transfusions for 7 days.
Time Frame
Up to 2 years
Title
Severe (grades III-IV) acute graft versus host disease (GVHD)
Description
Will be defined by the 2014 National Institutes of Health (NIH) criteria.
Time Frame
Up to 2 years
Title
Chronic GVHD
Description
Will be defined by the 2014 NIH criteria.
Time Frame
Up to 2 years
Title
Non-relapse mortality
Description
Will be defined as death without a prior relapse.
Time Frame
Up to day 180
Title
Human immunodeficiency virus (HIV) plasma viral load
Time Frame
Pre and post-transplant
Title
Immune homeostasis
Description
Concentration of immunity cells per microliters after transplant
Time Frame
Up to 2 years
Title
Immune reconstitution
Description
Concentration of immunity cells per microliters after transplant
Time Frame
Up to 2 years
Title
Change in HIV-1 induced inflammatory immune responses
Description
HIV viral load by PCR (copies per milliliter; mL)
Time Frame
Up to 2 years
Title
HIV rebound following antiretroviral therapy (ART) cessation
Description
HIV viral load by PCR (copies per milliliter; mL)
Time Frame
Up to 2 years
Title
Viral kinetics following ART cessation
Description
HIV viral load by PCR (copies per milliliter; mL)
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Filippo Milano
Phone
206.667.5925
Email
fmilano@fredhutch.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Filippo Milano
Organizational Affiliation
Fred Hutch/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Timothy Henrich
Email
Timothy.Henrich@ucsf.edu
First Name & Middle Initial & Last Name & Degree
Timothy Henrich
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Blachy Saldana
Email
BJDAVILA@childrensnational.org
First Name & Middle Initial & Last Name & Degree
Blachy Saldana
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Withdrawn
Facility Name
Case Western Reserve University
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kirsten Boughan
Email
Kirsten.Boughan@UHhospitals.org
First Name & Middle Initial & Last Name & Degree
Kirsten Boughan
Facility Name
Cleveland Cord Blood Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44128
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marcie Finney
Email
mfinney@clevelandcordblood.org
First Name & Middle Initial & Last Name & Degree
Mary Laughlin
Facility Name
Fred Hutch/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Filippo Milano
Phone
206-667-5925
Email
fmilano@fredhutch.org
First Name & Middle Initial & Last Name & Degree
Filippo Milano

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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