Clinical Trials /

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

NCT04083170

Description:

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.

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Chronic Myeloid Leukemia
  • Myelodysplastic Syndromes
  • Non-Hodgkin Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Cord Blood Transplant With OTS 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

Clinical Trial IDs

  • ORG STUDY ID: RG1004070
  • SECONDARY ID: P30CA015704
  • SECONDARY ID: NCI-2019-05729
  • NCT ID: NCT04083170

Conditions

  • 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

Interventions

DrugSynonymsArms
Fludarabine118218, 2-Fluoro-9-beta-arabinofuranosyladenine, 2-Fluorovidarabine, 9-Beta-D-arabinofuranosyl-2-fluoroadenine, FluradosaRegimen A (fludarabine, cyclophosphamide, TBI, OTS)
Fludarabine Phosphate2-F-ara-AMP, Beneflur, Fludara, Fludarabine-5''-Monophosphate, SH T 586Regimen A (fludarabine, cyclophosphamide, TBI, OTS)
CyclophosphamideCarloxan, 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, MitoxanRegimen A (fludarabine, cyclophosphamide, TBI, OTS)
ThiotepaSTEPA, Tepadina, TESPA, Tespamin, Tespamine, Thiofosfamide, Thio-Tepa, Thiofozil, Thiophosphamide, Thiophosphoramide, Thiotef, Tifosyl, Triethylene thiophosphoramide, Triethylenethiophosphoramide, TSPA, WR 45312Regimen B (fludarabine, cyclophosphamide, thiotepa, TBI, OTS)

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Regimen A (fludarabine, cyclophosphamide, TBI, OTS)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 umbilical cord blood-derived hematopoietic CD34-positive progenitor cells IV over 5-10 minutes in the absence of disease progression or unacceptable toxicity.
  • Fludarabine
  • Fludarabine Phosphate
  • Cyclophosphamide
Regimen B (fludarabine, cyclophosphamide, thiotepa, TBI, OTS)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 umbilical cord blood-derived hematopoietic CD34-positive progenitor cells IV over 5-10 minutes in the absence of disease progression or unacceptable toxicity.
  • Fludarabine
  • Fludarabine Phosphate
  • Cyclophosphamide
  • Thiotepa

Eligibility 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
      
Maximum Eligible Age:65 Years
Minimum Eligible Age:6 Months
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Primary graft failure rejection
Time Frame:Up to day 45
Safety Issue:
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.

Secondary Outcome Measures

Measure:Incidence of infusion toxicities
Time Frame:Within the first 24 hours after infusion
Safety Issue:
Description:Defined as Common Terminology Criteria for Adverse Events version 5.0 grade >= 3 events.
Measure:Neutrophil recovery
Time Frame:Up to 2 years
Safety Issue:
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.
Measure:Platelet engraftment
Time Frame:Up to 2 years
Safety Issue:
Description:Will be defined as the first day of a platelet count > 20,000/ul with subsequent transfusions for 7 days.
Measure:Severe (grades III-IV) acute graft versus host disease (GVHD)
Time Frame:Up to 2 years
Safety Issue:
Description:Will be defined by the 2014 National Institutes of Health (NIH) criteria.
Measure:Chronic GVHD
Time Frame:Up to 2 years
Safety Issue:
Description:Will be defined by the 2014 NIH criteria.
Measure:Non-relapse mortality
Time Frame:Up to day 180
Safety Issue:
Description:Will be defined as death without a prior relapse.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Fred Hutchinson Cancer Research Center

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