- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04083170
Cord Blood Transplant With Dilanubicel for the Treatment of HIV Positive Hematologic Cancers
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 Overview
Status
Conditions
- HIV Infection
- Hematopoietic and Lymphoid Cell Neoplasm
- Acute Myeloid Leukemia
- Acute Lymphoblastic Leukemia
- Acute Erythroid Leukemia
- Acute Megakaryoblastic Leukemia
- Non-Hodgkin Lymphoma
- Myelodysplastic Syndrome
- Myelodysplastic Syndrome With Excess Blasts
- Chronic Myelogenous Leukemia, BCR-ABL1 Positive
- Refractory Anemia
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.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Filippo Milano
- Phone Number: 206.667.5925
- Email: fmilano@fredhutch.org
Study Locations
-
-
California
-
San Francisco, California, United States, 94143
- Not yet recruiting
- University of California San Francisco
-
Contact:
- Timothy Henrich
- Email: Timothy.Henrich@ucsf.edu
-
Principal Investigator:
- Timothy Henrich
-
-
District of Columbia
-
Washington, District of Columbia, United States, 20010
- Not yet recruiting
- Children's National Medical Center
-
Contact:
- Blachy Saldana
- Email: BJDAVILA@childrensnational.org
-
Principal Investigator:
- Blachy Saldana
-
-
New York
-
New York, New York, United States, 10065
- Withdrawn
- Memorial Sloan Kettering Cancer Center
-
-
Ohio
-
Cleveland, Ohio, United States, 44106
- Not yet recruiting
- Case Western Reserve University
-
Contact:
- Kirsten Boughan
- Email: Kirsten.Boughan@UHhospitals.org
-
Principal Investigator:
- Kirsten Boughan
-
Cleveland, Ohio, United States, 44128
- Recruiting
- Cleveland Cord Blood Center
-
Contact:
- Marcie Finney
- Email: mfinney@clevelandcordblood.org
-
Principal Investigator:
- Mary Laughlin
-
-
Washington
-
Seattle, Washington, United States, 98109
- Recruiting
- Fred Hutch/University of Washington Cancer Consortium
-
Contact:
- Filippo Milano
- Phone Number: 206-667-5925
- Email: fmilano@fredhutch.org
-
Principal Investigator:
- Filippo Milano
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Regimen A (fludarabine, cyclophosphamide, TBI, dilanubcel)
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.
|
Given IV
Other Names:
Given IV
Other Names:
Undergo TBI
Other Names:
Undergo UCBT
Other Names:
Given IV
Other Names:
|
Experimental: Regimen B (anticancer drugs, TBI, 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.
|
Given IV
Other Names:
Given IV
Other Names:
Undergo TBI
Other Names:
Given IV
Other Names:
Undergo UCBT
Other Names:
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Up to day 45
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Within the first 24 hours after infusion
|
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.
|
Up to 2 years
|
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.
|
Up to 2 years
|
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.
|
Up to 2 years
|
Chronic GVHD
Time Frame: Up to 2 years
|
Will be defined by the 2014 NIH criteria.
|
Up to 2 years
|
Non-relapse mortality
Time Frame: Up to day 180
|
Will be defined as death without a prior relapse.
|
Up to day 180
|
Human immunodeficiency virus (HIV) plasma viral load
Time Frame: Pre and post-transplant
|
Pre and post-transplant
|
|
Immune homeostasis
Time Frame: Up to 2 years
|
Concentration of immunity cells per microliters after transplant
|
Up to 2 years
|
Immune reconstitution
Time Frame: Up to 2 years
|
Concentration of immunity cells per microliters after transplant
|
Up to 2 years
|
Change in HIV-1 induced inflammatory immune responses
Time Frame: Up to 2 years
|
HIV viral load by PCR (copies per milliliter; mL)
|
Up to 2 years
|
HIV rebound following antiretroviral therapy (ART) cessation
Time Frame: Up to 2 years
|
HIV viral load by PCR (copies per milliliter; mL)
|
Up to 2 years
|
Viral kinetics following ART cessation
Time Frame: Up to 2 years
|
HIV viral load by PCR (copies per milliliter; mL)
|
Up to 2 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Filippo Milano, Fred Hutch/University of Washington Cancer Consortium
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Disease Attributes
- Disease
- Bone Marrow Diseases
- Hematologic Diseases
- Myeloproliferative Disorders
- Anemia
- Precancerous Conditions
- Leukemia, Lymphoid
- Leukemia, Myeloid, Acute
- Chronic Disease
- Syndrome
- Myelodysplastic Syndromes
- Leukemia
- Leukemia, Myeloid
- Preleukemia
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Leukemia, Megakaryoblastic, Acute
- Leukemia, Erythroblastic, Acute
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Anemia, Refractory, with Excess of Blasts
- Anemia, Refractory
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Cyclophosphamide
- Fludarabine
- Fludarabine phosphate
- Thiotepa
- Vidarabine
Other Study ID Numbers
- RG1004070
- NCI-2019-05729 (Registry Identifier: NCI / CTRP)
- R34HL142322 (U.S. NIH Grant/Contract)
- 10304 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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