Donor Umbilical Cord Blood Transplant With or Without Ex-Vivo Expanded Cord Blood Progenitor Cells in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, or Myelodysplastic Syndromes

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01690520
First received: September 19, 2012
Last updated: October 9, 2014
Last verified: October 2014
  Purpose

This randomized phase II trial studies how well donor umbilical cord blood transplant with or without ex-vivo expanded cord blood progenitor cells works in treating patients with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, or myelodysplastic syndromes. Giving chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's cells. When the healthy stem cells and ex-vivo expanded cord blood progenitor cells are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. It is not yet known whether giving donor umbilical cord blood transplant plus ex-vivo expanded cord blood progenitor cells is more effective than giving a donor umbilical cord blood transplant alone.


Condition Intervention Phase
Accelerated Phase Chronic Myelogenous Leukemia
Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome
Adult Acute Lymphoblastic Leukemia in Remission
Adult Acute Myeloid Leukemia in Remission
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Del(5q)
Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Childhood Acute Lymphoblastic Leukemia in Remission
Childhood Acute Myeloid Leukemia in Remission
Childhood Chronic Myelogenous Leukemia
Chronic Phase Chronic Myelogenous Leukemia
de Novo Myelodysplastic Syndromes
Previously Treated Myelodysplastic Syndromes
Refractory Anemia
Refractory Anemia With Excess Blasts
Refractory Anemia With Excess Blasts in Transformation
Relapsing Chronic Myelogenous Leukemia
Secondary Acute Myeloid Leukemia
Drug: fludarabine phosphate
Drug: cyclophosphamide
Radiation: total-body irradiation
Procedure: ex vivo-expanded cord blood progenitor cell infusion
Procedure: umbilical cord blood transplantation
Procedure: double-unit umbilical cord blood transplantation
Drug: cyclosporine
Drug: mycophenolate mofetil
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multi-center, Open-Label Randomized Study of Single or Double Myeloablative Cord Blood Transplantation With or Without Infusion of Off-The-Shelf Ex Vivo Expanded Cryopreserved Cord Blood Progenitor Cells in Patients With Hematologic Malignancies

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Time to engraftment (ANC greater than or equal to 500) in both arms (standard myeloablative CBT with and without off-the-shelf expanded cord blood progenitors) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    The log-rank test will be used. Groups will be compared using Gray's test.


Secondary Outcome Measures:
  • Time to engraftment, defined as the first of 2 consecutive days in which ANC is at least 500 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Groups will be compared using Gray's test.

  • Relative contribution to engraftment of the expanded cord blood product and the unmanipulated cord blood unit(s) in early and long-term engraftment, determined by frequent determination of donor chimerism in the peripheral blood [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Groups will be compared using Gray's test.

  • Time to ANC greater than or equal to 100 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Time to ANC greater than or equal to 500 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Time to platelet engraftment (20k and 50k) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Duration of initial hospitalization [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Incidence of infectious complications [ Time Frame: Up to 100 days post-transplant ] [ Designated as safety issue: No ]
  • Non-relapse mortality (NRM) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Incidence and severity of acute and chronic GVHD [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
  • Infusional toxicity greater than or equal to grade 3 [ Time Frame: Day 0 (day of transplant) ] [ Designated as safety issue: Yes ]
    Toxicities will be graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.

  • Graft failure (primary and secondary) [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
  • Kinetics of immune system recovery as measured by T and B cell subsets, T cell receptor excision circles (TREC), and T cell receptor (TCR) sequencing [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    The kinetics and durability of hematopoietic reconstitution will be assessed and the relative contribution to engraftment of the expanded cord blood product and the unmanipulated unit(s) will be determined by frequent peripheral blood donor chimerism assays.

  • Death without engraftment [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Groups will be compared using Gray's test and log-rank test.


Estimated Enrollment: 160
Study Start Date: December 2012
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (standard of care)

CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6 and cyclophosphamide IV on days -7 to -6. Patients also undergo TBI BID on days -4 to -1.

TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0.

GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit.

Drug: fludarabine phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Radiation: total-body irradiation
Undergo TBI
Other Name: TBI
Procedure: umbilical cord blood transplantation
Undergo single-unit unmanipulated umbilical cord blood transplant
Other Names:
  • cord blood transplantation
  • transplantation, umbilical cord blood
  • UCB transplantation
Procedure: double-unit umbilical cord blood transplantation
Undergo double-unit unmanipulated umbilical cord blood transplant
Drug: cyclosporine
Given IV
Other Names:
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune
Drug: mycophenolate mofetil
Given IV or PO
Other Names:
  • Cellcept
  • MMF
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II (experimental)

CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV and cyclophosphamide IV, and undergo TBI as in Standard of Care Arm.

TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant.

GVHD PROPHYLAXIS: Patients receive cyclosporine IV and mycophenolate mofetil IV or PO as in Standard of Care Arm.

Drug: fludarabine phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Radiation: total-body irradiation
Undergo TBI
Other Name: TBI
Procedure: ex vivo-expanded cord blood progenitor cell infusion
Given IV
Procedure: umbilical cord blood transplantation
Undergo single-unit unmanipulated umbilical cord blood transplant
Other Names:
  • cord blood transplantation
  • transplantation, umbilical cord blood
  • UCB transplantation
Procedure: double-unit umbilical cord blood transplantation
Undergo double-unit unmanipulated umbilical cord blood transplant
Drug: cyclosporine
Given IV
Other Names:
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune
Drug: mycophenolate mofetil
Given IV or PO
Other Names:
  • Cellcept
  • MMF
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Compare the time to neutrophil engraftment (absolute neutrophil count [ANC] >= 500) in patients receiving a standard of care myeloablative cord blood transplant (CBT) augmented with an off-the-shelf pre-expanded and cryopreserved cord blood product to those who do not receive the product.

SECONDARY OBJECTIVES:

I. Provide initial data on clinical and economic benefit, such as time to platelet engraftment, duration of initial hospitalization, day 200 transplant related mortality (TRM), death without engraftment, and incidence of severe infections in the first 100 days post-transplant.

II. The kinetics of immune system recovery will also be evaluated in both arms.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

Standard of Care Arm:

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -8 to -6 and cyclophosphamide IV on days -7 to -6. Patients also undergo total-body irradiation (TBI) twice daily (BID) on days -4 to -1.

TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated umbilical cord blood (UCB) transplant on day 0.

GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or thrice daily (TID) (children) on days -3 to 100 with taper beginning on day 101. Patients also receive mycophenolate mofetil (MMF) IV TID on days 0-7 then may receive MMF orally (PO) TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin taper if there is no evidence of graft-versus-host disease (GVHD) and are well-engrafted from one donor unit.

Experimental Arm:

CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV and cyclophosphamide IV, and undergo TBI as in Standard of Care Arm.

TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also receive an infusion of ex vivo-expanded cord blood progenitors at least 4 hours after completion of UCB transplant.

GVHD PROPHYLAXIS: Patients receive cyclosporine IV and mycophenolate mofetil IV or PO as in Standard of Care Arm.

After completion of study treatment, patients are followed up periodically for 2 years.

  Eligibility

Ages Eligible for Study:   6 Months to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Acute myeloid leukemia

    • High risk first complete remission (CR1) as evidenced by preceding myelodysplastic syndromes (MDS), high risk cytogenetics (for example, monosomy 5 or 7, or as defined by referring institution treatment protocol), >= 2 cycles to obtain complete remission (CR), erythroblastic or megakaryocytic leukemia; >= second complete remission (CR2)
    • All patients must be in CR as defined by < 5% blasts by morphology/flow cytometry in a representative bone marrow sample with cellularity >= 15% for age
    • 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; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures; these patients must be discussed with the principal investigator 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); or high risk (HR) as defined by referring institution treatment protocol greater than 1 cycle to obtain CR; CR2 or greater
    • All patients must be in CR as defined by < 5% blasts by morphology/flow cytometry in a representative bone marrow sample with cellularity >= 15% for age
    • 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; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures; these patients must be discussed with the principal investigator 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 tyrosine kinase inhibitor therapy
  • 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
  • Karnofsky (>= 16 years old) >= 70 or Eastern Cooperative Oncology Group (ECOG) 0-1
  • Lansky (< 16 years old) >= 60
  • 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 < 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 referring institution
  • Diffusing capacity of the lung for carbon monoxide (DLCO) corrected > 60% normal
  • For pediatric patients unable to perform pulmonary function tests, oxygen (O2) saturation > 92% on room air
  • May not be on supplemental oxygen
  • Left ventricular ejection fraction > 45% OR
  • Shortening fraction > 26%
  • Ability to understand and the willingness to sign a written informed consent document

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
  • History of human immunodeficiency virus (HIV) infection
  • Pregnant or breastfeeding
  • Prior myeloablative transplant containing full dose TBI (greater than 8 Gy)
  • Any prior myeloablative transplant within the last 6 months
  • Central nervous system (CNS) leukemic involvement not clearing with intrathecal chemotherapy and/or cranial radiation prior to initiation of conditioning; diagnostic lumbar puncture is to be performed per protocol
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01690520

Locations
United States, California
City of Hope Medical Center Not yet recruiting
Duarte, California, United States, 91010
Contact: Chatchada Karanes    626-359-8111 ext 62691    becomingapatient@coh.org   
Principal Investigator: Chatchada Karanes         
United States, Colorado
University of Colorado Recruiting
Denver, Colorado, United States, 80217-3364
Contact: Jonathan A. Gutman    720-848-0644      
Principal Investigator: Jonathan A. Gutman         
United States, Massachusetts
Dana-Farber Harvard Cancer Center Not yet recruiting
Boston, Massachusetts, United States, 02115
Contact: Christine N. Duncan    617-632-6255      
Principal Investigator: Christine N. Duncan         
United States, North Carolina
Duke University Medical Center Not yet recruiting
Durham, North Carolina, United States, 27710
Contact: Joanne Kurtzberg    919-668-1100      
Principal Investigator: Joanne Kurtzberg         
United States, Ohio
Cleveland Clinic Foundation Not yet recruiting
Cleveland, Ohio, United States, 44195
Contact: Rabi Hanna    216-444-0663      
Principal Investigator: Rabi Hanna         
United States, Tennessee
Vanderbilt-Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Haydar A. Frangoul    615-936-1762      
Principal Investigator: Haydar A. Frangoul         
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Colleen Delaney    206-667-1385      
Principal Investigator: Colleen Delaney         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Colleen Delaney Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01690520     History of Changes
Other Study ID Numbers: 2603.00, NCI-2012-01572, 2603, 2603.00, P30CA015704, P50HL110787
Study First Received: September 19, 2012
Last Updated: October 9, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Anemia
Anemia, Refractory
Anemia, Refractory, with Excess of Blasts
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myeloid, Accelerated Phase
Leukemia, Myeloid, Acute
Leukemia, Myeloid, Chronic-Phase
Myelodysplastic Syndromes
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions
Cyclophosphamide
Cyclosporine

ClinicalTrials.gov processed this record on October 23, 2014