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Infusion of Expanded Cord Blood Cells in Addition to Single Cord Blood Transplant in Treating Patients With Acute Leukemia, Chronic Myeloid Leukemia, or Myelodysplastic Syndromes

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ClinicalTrials.gov Identifier: NCT03399773
Recruitment Status : Not yet recruiting
First Posted : January 16, 2018
Last Update Posted : March 29, 2018
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 how well donor umbilical cord blood transplant with ex-vivo expanded cord blood progenitor cells (NLA101) works in treating patients with blood cancer. Before the transplant, patients will receive chemotherapy (fludarabine, cyclophosphamide and in some cases thiotepa) and radiation therapy. Giving chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells.

Condition or disease Intervention/treatment Phase
Acute Biphenotypic Leukemia Acute Lymphoblastic Leukemia in Remission Acute Myeloid Leukemia in Remission Blasts Under 10 Percent of Bone Marrow Nucleated Cells Blasts Under 5 Percent of Bone Marrow Nucleated Cells Chronic Myelogenous Leukemia, BCR-ABL1 Positive Cytogenetic Abnormality High Risk Myelodysplastic Syndrome Myelodysplastic Syndrome With Excess Blasts Pancytopenia Refractory Anemia Drug: Cyclophosphamide Drug: Fludarabine Other: Laboratory Biomarker Analysis Drug: Thiotepa Radiation: Total-Body Irradiation Procedure: Umbilical Cord Blood Transplantation Biological: Umbilical Cord Blood-derived Hematopoietic CD34-positive Progenitor Cells Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. Primary graft failure/rejection as 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 [BM]) by day 45.

SECONDARY OBJECTIVES:

I. Examine the safety and toxicity of infusing NLA101.

II. Neutrophil and platelet engraftment.

III. Incidence of acute graft versus host disease (GVHD) at day 100 and chronic GVHD at 1 year.

IV. Non-relapse mortality at day 100 and 180.

OUTLINE:

Patients receive either regimen A or regimen B.

REGIMEN A: Patients (18 through 45 years old) receive fludarabine intravenously (IV) over 30 minutes on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo total body irradiation (TBI) twice daily (BID) on days -4 to -1. Patients receive unmanipulated cord blood unit IV followed by NLA101 IV within the next 24 hours on day 0.

REGIMEN B: Patients (18 through 65 years old) receive fludarabine IV over 30-60 minutes on days -6 to -3 and IV over 30 minutes on day -2, cyclophosphamide IV on day -6, and thiotepa IV over 4 hours on days -5 and -4. Patients receive unmanipulated cord blood unit IV followed by NLA101 IV within the next 24 hours on day 0.

After completion of study treatment, patients are followed up at 180 days, 1 year, and 2 years.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Infusion of Off the Shelf Ex Vivo Expanded Cryopreserved Progenitor Cells (NLA101) in the Setting of Single Cord Blood Transplantation for Patients With Hematologic Malignancies
Estimated Study Start Date : May 15, 2018
Estimated Primary Completion Date : March 15, 2022
Estimated Study Completion Date : March 15, 2022


Arm Intervention/treatment
Experimental: Treatment (chemotherapy, TBI, NLA101)

Patients receive either regimen A or regimen B.

REGIMEN A: Patients (18 through 45 years old) receive fludarabine IV over 30 minutes on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo TBI BID on days -4 to -1. Patients receive unmanipulated cord blood unit IV followed by NLA101 IV within the next 24 hours on day 0.

REGIMEN B: Patients (18 through 65 years old) receive fludarabine IV over 30-60 minutes on days -6 to -3 and IV over 30 minutes on day -2, cyclophosphamide IV on day -6, and thiotepa IV over 4 hours on days -5 and -4. Patients receive unmanipulated cord blood unit IV followed by NLA101 IV within the next 24 hours on day 0.

Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719

Drug: Fludarabine
Given IV
Other Name: Fluradosa

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Thiotepa
Given IV
Other Names:
  • 1,1',1''-Phosphinothioylidynetrisaziridine
  • Girostan
  • N,N', N''-Triethylenethiophosphoramide
  • Oncotiotepa
  • STEPA
  • Tepadina
  • TESPA
  • Tespamin
  • Tespamine
  • Thio-Tepa
  • Thiofosfamide
  • Thiofozil
  • Thiophosphamide
  • Thiophosphoramide
  • Thiotef
  • Tifosyl
  • TIO TEF
  • Tio-tef
  • Triethylene thiophosphoramide
  • Triethylenethiophosphoramide
  • Tris(1-aziridinyl)phosphine sulfide
  • TSPA
  • WR 45312

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

Procedure: Umbilical Cord Blood Transplantation
Given IV
Other Names:
  • Cord Blood Transplantation
  • UCB transplantation

Biological: Umbilical Cord Blood-derived Hematopoietic CD34-positive Progenitor Cells
Given IV
Other Names:
  • Ex Vivo-expanded Umbilical Cord Blood-derived Hematopoietic CD34-positive Progenitor Cells
  • NiCord
  • UCB-derived CD34+ HPCs




Primary Outcome Measures :
  1. Graft failure [ Time Frame: Up to day 45 post-transplant ]
    Primary graft failure/rejection as defined by no neutrophil recovery (regardless of donor chimerism) or autologous recovery (neutrophil recovery but < 10% donor chimerism in blood and bone marrow [BM]).

  2. Incidence and severity of acute graft versus host disease (GVHD) [ Time Frame: At day 100 post-transplant ]
    Assessed using the Acute GVHD Grading Scale (reference: Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant 1995; 15: 825-8).

  3. Incidence and severity of chronic graft versus host disease (GVHD) [ Time Frame: Up to approximately 2 years post-transplant ]
    Assessed using the Chronic GVHD Grading Scale (reference: Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease. I. Diagnosis and Staging Working Group report. Blood Marrow Transplant 2005; 11: 945-56).


Secondary Outcome Measures :
  1. Neutrophil engraftment [ Time Frame: Up to day 45 post-transplant ]
    The day of neutrophil recovery will be the 1st day of 2 consecutive days of absolute neutrophil count at or above 500 after the 1st post-cord blood transplant nadir.

  2. Platelet engraftment measured by the number of participants with a platelet count > 20,000/μl without subsequent transfusions for 7 days [ Time Frame: Up to day 100 post-transplant ]
  3. Incidence of adverse events [ Time Frame: Up to day 100 post-transplant ]
    Toxicities will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0.

  4. Non-relapse mortality [ Time Frame: At day 100 post-transplant ]
  5. Non-relapse mortality [ Time Frame: At 1 year post-transplant ]


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient must have hematologic malignancy that meets institutional eligibility requirements for cord blood transplant
  • Malignancies included are:

    • Acute leukemia, including Acute myeloid leukemia (AML), biphenotypic acute leukemia or mixed-lineage leukemia, acute lymphoblastic leukemia (ALL); all patients must be in complete response (CR) as defined by < 5% blasts by morphology/flow cytometry in a representative bone marrow sample with adequate cellularity to assess remission status
    • Myelodysplasia (MDS) International Prognostic Scoring System (IPSS) intermediate (Int)-2 or high risk (i.e., RAEB, RAEBt) or refractory anemia with severe pancytopenia or high risk cytogenetics; blasts must be < 10% by a representative bone marrow aspirate morphology
    • Chronic Myeloid Leukemia excluding refractory blast crisis; to be eligible in first chronic phase (CP1) patient must have failed or be intolerant to tyrosine kinase inhibitor therapy
  • High dose TBI regimen: 18 to =< 45 years
  • Intermediate intensity regimen: 18 =< 65 years
  • Patients 18 to =< 45 years: Karnofsky (>= 18 years old) >= 70 or Eastern Cooperative Oncology Group (ECOG) 0-1
  • Patients > 45 to =< 65 years: Karnofsky >= 70 or ECOG 0-1 and non-age adjusted comorbidity index =< 5
  • Calculated creatinine clearance must be > 60 mL and serum creatinine =< 2 mg/dL
  • Total serum bilirubin must be < 3mg/dL unless the elevation is thought to be due to Gilbert's disease or hemolysis
  • Transaminases must be < 3 x the upper limit of normal per reference values of treating institution
  • Carbon monoxide diffusing capability (DLCO) corrected >= 60% normal (may not be on supplemental oxygen)
  • Left ventricular ejection fraction >= 50% OR
  • Shortening fraction > 26%
  • Ability to understand and the willingness to sign a written informed consent form
  • DONOR: Minimum requirement: The cord blood (CB) unit must be matched at a minimum at 4/6 HLA-A, B antigens and DRB1 allele with the recipient; therefore, 0-2 mismatches at the A or B or DRB1 loci based on intermediate resolution at HLA-A, B and high resolution allele level typing at HLA- DRB1 are allowed
  • DONOR: Institutional guidelines for HLA-match may be followed as long as the minimum criteria for HLA-matching as above are met
  • DONOR: The CB unit selected for transplant must have a MINIMUM of 2.5 x 10^7 TNC/kg
  • DONOR: The minimum recommended CD34/kg cell dose is 1.7 x 10^5 CD34/kg
  • DONOR: A domestic backup unit must be identified and reserved prior to the start of the treatment plan for possible infusion in the unlikely event of poor post-thaw viability of the primary CB unit

Exclusion Criteria:

  • Uncontrolled viral or bacterial infection at the time of study enrollment
  • Active or recent (prior 6 month) invasive fungal infection unless cleared by innovation and development (ID) consult
  • History of human immunodeficiency virus (HIV) infection
  • Pregnant or breastfeeding
  • Prior allogeneic transplant
  • Central nervous system (CNS) leukemic involvement not clearing with intrathecal chemotherapy; diagnostic lumbar puncture is 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): NCT03399773


Locations
United States, New York
Memorial Sloan Kettering Cancer Center Not yet recruiting
New York, New York, United States, 10065
Contact: Juliet N. Barker         
Principal Investigator: Juliet N. Barker         
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
Principal Investigator: Filippo Milano Fred Hutch/University of Washington Cancer Consortium

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT03399773     History of Changes
Other Study ID Numbers: 9910
NCI-2017-02205 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
9910 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
P50HL110787 ( U.S. NIH Grant/Contract )
First Posted: January 16, 2018    Key Record Dates
Last Update Posted: March 29, 2018
Last Verified: March 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Syndrome
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Anemia, Refractory
Pancytopenia
Anemia, Refractory, with Excess of Blasts
Chromosome Aberrations
Chromosome Disorders
Leukemia, Biphenotypic, Acute
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Myeloproliferative Disorders
Anemia
Congenital Abnormalities
Genetic Diseases, Inborn