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 June 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: June 20, 2014
Last verified: June 2014

September 19, 2012
June 20, 2014
December 2012
October 2017   (final data collection date for primary outcome measure)
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.
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.
Complete list of historical versions of study NCT01690520 on ClinicalTrials.gov Archive Site
  • 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.
  • 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 ]
  • 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 ]
  • 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) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Time to platelet engraftment (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: Day 200 ] [ Designated as safety issue: No ]
  • NRM [ Time Frame: 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: Up to 2 years ] [ Designated as safety issue: Yes ]
  • 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), spectratyping and T cell receptor (TCR) sequencing [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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
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

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
    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
  • 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.

    Interventions:
    • Drug: fludarabine phosphate
    • Drug: cyclophosphamide
    • Radiation: total-body irradiation
    • Procedure: umbilical cord blood transplantation
    • Procedure: double-unit umbilical cord blood transplantation
    • Drug: cyclosporine
    • Drug: mycophenolate mofetil
    • Other: laboratory biomarker analysis
  • 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.

    Interventions:
    • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
160
Not Provided
October 2017   (final data collection date for primary outcome measure)

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 hematologic recovery and < 5% blasts by morphology within the bone marrow and a cellularity of >= 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 hematologic recovery and < 5% blasts by morphology within the bone marrow and a cellularity of >= 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
Both
6 Months to 45 Years
No
United States
 
NCT01690520
2603.00, NCI-2012-01572, 2603.00, P30CA015704, P50HL110787
Yes
Fred Hutchinson Cancer Research Center
Fred Hutchinson Cancer Research Center
  • National Heart, Lung, and Blood Institute (NHLBI)
  • National Cancer Institute (NCI)
Principal Investigator: Colleen Delaney Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Fred Hutchinson Cancer Research Center
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP