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

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ClinicalTrials.gov Identifier: NCT04083170
Recruitment Status : Not yet recruiting
First Posted : September 10, 2019
Last Update Posted : September 10, 2019
Sponsor:
Collaborators:
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center

Brief Summary:
This phase II trial studies the side effects of a cord blood transplant using OTS 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. OTS 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 OTS 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.

Condition or disease Intervention/treatment Phase
Acute Erythroid Leukemia Acute Lymphoblastic Leukemia Acute Megakaryoblastic Leukemia Acute Myeloid Leukemia Blasts Under 10 Percent of Bone Marrow Nucleated Cells Blasts Under 5 Percent of Bone Marrow Nucleated Cells Chronic Myelogenous Leukemia, BCR-ABL1 Positive Hematopoietic and Lymphoid Cell Neoplasm Human Immunodeficiency Virus Positive Myelodysplastic Syndrome Myelodysplastic Syndrome With Excess Blasts Non-Hodgkin Lymphoma Refractory Anemia Drug: Fludarabine Drug: Fludarabine Phosphate Drug: Cyclophosphamide Drug: Thiotepa Radiation: Total-Body Irradiation Procedure: Umbilical Cord Blood Transplantation Other: Cellular Therapy Phase 2

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 umbilical cord blood-derived hematopoietic CD34-positive progenitor cells 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 umbilical cord blood-derived hematopoietic CD34-positive progenitor cells 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : September 30, 2019
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2022


Arm Intervention/treatment
Experimental: Regimen A (fludarabine, cyclophosphamide, TBI, OTS)
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 umbilical cord blood-derived hematopoietic CD34-positive progenitor cells IV over 5-10 minutes in the absence of disease progression or unacceptable toxicity.
Drug: Fludarabine
Given IV
Other Names:
  • 118218
  • 2-Fluoro-9-beta-arabinofuranosyladenine
  • 2-Fluorovidarabine
  • 9-Beta-D-arabinofuranosyl-2-fluoroadenine
  • Fluradosa

Drug: Fludarabine Phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
  • Fludarabine-5''-Monophosphate
  • SH T 586

Drug: Cyclophosphamide
Given IV
Other Names:
  • 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

Radiation: Total-Body Irradiation
Undergo TBI
Other Names:
  • TBI
  • TOTAL BODY IRRADIATION
  • Whole Body Irradiation
  • Whole-Body Irradiation

Procedure: Umbilical Cord Blood Transplantation
Undergo UCBT
Other Names:
  • Cord Blood Transplantation
  • UCB transplantation

Other: Cellular Therapy
Given OTS IV
Other Name: Cell Therapy

Experimental: Regimen B (fludarabine, cyclophosphamide, thiotepa, TBI, OTS)
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 umbilical cord blood-derived hematopoietic CD34-positive progenitor cells IV over 5-10 minutes in the absence of disease progression or unacceptable toxicity.
Drug: Fludarabine
Given IV
Other Names:
  • 118218
  • 2-Fluoro-9-beta-arabinofuranosyladenine
  • 2-Fluorovidarabine
  • 9-Beta-D-arabinofuranosyl-2-fluoroadenine
  • Fluradosa

Drug: Fludarabine Phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
  • Fludarabine-5''-Monophosphate
  • SH T 586

Drug: Cyclophosphamide
Given IV
Other Names:
  • 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

Drug: Thiotepa
Given IV
Other Names:
  • STEPA
  • Tepadina
  • TESPA
  • Tespamin
  • Tespamine
  • Thiofosfamide
  • Thio-Tepa
  • Thiofozil
  • Thiophosphamide
  • Thiophosphoramide
  • Thiotef
  • Tifosyl
  • Triethylene thiophosphoramide
  • Triethylenethiophosphoramide
  • TSPA
  • WR 45312

Radiation: Total-Body Irradiation
Undergo TBI
Other Names:
  • TBI
  • TOTAL BODY IRRADIATION
  • Whole Body Irradiation
  • Whole-Body Irradiation

Procedure: Umbilical Cord Blood Transplantation
Undergo UCBT
Other Names:
  • Cord Blood Transplantation
  • UCB transplantation

Other: Cellular Therapy
Given OTS IV
Other Name: Cell Therapy




Primary Outcome Measures :
  1. Primary graft failure rejection [ Time Frame: Up to day 45 ]
    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 :
  1. Incidence of infusion toxicities [ Time Frame: Within the first 24 hours after infusion ]
    Defined as Common Terminology Criteria for Adverse Events version 5.0 grade >= 3 events.

  2. Neutrophil recovery [ Time Frame: Up to 2 years ]
    Will be defined as the first day of 2 consecutive days of absolute neutrophil count >= 500 after the first post-cord blood transplant nadir.

  3. Platelet engraftment [ Time Frame: Up to 2 years ]
    Will be defined as the first day of a platelet count > 20,000/ul with subsequent transfusions for 7 days.

  4. Severe (grades III-IV) acute graft versus host disease (GVHD) [ Time Frame: Up to 2 years ]
    Will be defined by the 2014 National Institutes of Health (NIH) criteria.

  5. Chronic GVHD [ Time Frame: Up to 2 years ]
    Will be defined by the 2014 NIH criteria.

  6. Non-relapse mortality [ Time Frame: Up to day 180 ]
    Will be defined as death without a prior relapse.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   6 Months to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • For pediatric patients unable to perform pulmonary function tests, oxygen (O2) saturation > 92% on room air
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04083170


Contacts
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Contact: Filippo Milano 206.667.5925 fmilano@fredhutch.org

Locations
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United States, Washington
Fred Hutch/University of Washington Cancer Consortium Not yet recruiting
Seattle, Washington, United States, 98109
Contact: Filippo Milano         
Principal Investigator: Filippo Milano         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Filippo Milano Fred Hutch/University of Washington Cancer Consortium

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Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT04083170     History of Changes
Other Study ID Numbers: RG1004070
P30CA015704 ( U.S. NIH Grant/Contract )
NCI-2019-05729 ( Registry Identifier: NCI / CTRP )
First Posted: September 10, 2019    Key Record Dates
Last Update Posted: September 10, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Acquired Immunodeficiency Syndrome
HIV Infections
HIV Seropositivity
Leukemia
Preleukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Megakaryoblastic, Acute
Leukemia, Erythroblastic, Acute
Myelodysplastic Syndromes
Anemia, Refractory
Anemia, Refractory, with Excess of Blasts
Syndrome
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, Lymphoid
Immunologic Deficiency Syndromes
Myeloproliferative Disorders
Lentivirus Infections