Cord Blood Transplant With Dilanubicel for the Treatment of HIV Positive Hematologic Cancers
- Conditions
- Interventions
- Registration Number
- NCT04083170
- Lead Sponsor
- Fred Hutchinson Cancer Center
- 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 ri...
- Detailed Description
OUTLINE: Patients are assigned to 1 of 2 regimens.
...
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 1
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>= 6 months to =< 65 years
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Treatment with combination antiretroviral therapy (cART) for at least 1 month before enrollment
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Viral load < 5000 copies/ml plasma on cART
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Disease criteria
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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
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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
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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
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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
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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
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Karnofsky (>= 16 years old) >= 70%
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Lansky (< 16 years old) >= 50%
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Adults: Calculated creatinine clearance must be > 60 mL and serum creatinine =< 2 mg/dL
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Children (< 18 years old): Calculated creatinine clearance must be > 60 mL/min
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Total serum bilirubin must be < 3 mg/dL
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Transaminases must be < 3 x the upper limit of normal
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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
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Left ventricular ejection fraction > 45% OR
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Shortening fraction > 26%
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Ability to understand and the willingness to sign a written informed consent document (adult subject or parent/legal guardian of minor subject)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Regimen A (fludarabine, cyclophosphamide, TBI, dilanubcel) Umbilical Cord Blood Transplantation 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. Regimen A (fludarabine, cyclophosphamide, TBI, dilanubcel) Dilanubicel 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. Regimen A (fludarabine, cyclophosphamide, TBI, dilanubcel) Total-Body Irradiation 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. Regimen B (anticancer drugs, TBI, dilanubicel) Total-Body Irradiation 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. Regimen B (anticancer drugs, TBI, dilanubicel) Dilanubicel 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. Regimen B (anticancer drugs, TBI, dilanubicel) Umbilical Cord Blood Transplantation 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. Regimen A (fludarabine, cyclophosphamide, TBI, dilanubcel) Fludarabine 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. Regimen A (fludarabine, cyclophosphamide, TBI, dilanubcel) Cyclophosphamide 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. Regimen B (anticancer drugs, TBI, dilanubicel) Fludarabine 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. Regimen B (anticancer drugs, TBI, dilanubicel) Cyclophosphamide 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. Regimen B (anticancer drugs, TBI, dilanubicel) Thiotepa 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.
- Primary Outcome Measures
Name Time Method Primary graft failure rejection 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
Name Time Method HIV rebound following antiretroviral therapy (ART) cessation Up to 2 years HIV viral load by PCR (copies per milliliter; mL)
Incidence of infusion toxicities Within the first 24 hours after infusion Defined as Common Terminology Criteria for Adverse Events version 5.0 grade \>= 3 events.
Neutrophil recovery 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.
Severe (grades III-IV) acute graft versus host disease (GVHD) Up to 2 years Will be defined by the 2014 National Institutes of Health (NIH) criteria.
Non-relapse mortality Up to day 180 Will be defined as death without a prior relapse.
Immune homeostasis Up to 2 years Concentration of immunity cells per microliters after transplant
Viral kinetics following ART cessation Up to 2 years HIV viral load by PCR (copies per milliliter; mL)
Platelet engraftment Up to 2 years Will be defined as the first day of a platelet count \> 20,000/ul with subsequent transfusions for 7 days.
Chronic GVHD Up to 2 years Will be defined by the 2014 NIH criteria.
Human immunodeficiency virus (HIV) plasma viral load Pre and post-transplant Immune reconstitution Up to 2 years Concentration of immunity cells per microliters after transplant
Change in HIV-1 induced inflammatory immune responses Up to 2 years HIV viral load by PCR (copies per milliliter; mL)
Trial Locations
- Locations (5)
Fred Hutch/University of Washington Cancer Consortium
🇺🇸Seattle, Washington, United States
Cleveland Cord Blood Center
🇺🇸Cleveland, Ohio, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States