Donor Umbilical Cord Blood Transplant After Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation in Treating Patients With High-Risk Hematologic Cancer

Sponsor
Masonic Cancer Center, University of Minnesota (Other)
Overall Status
Terminated
CT.gov ID
NCT00963872
Collaborator
National Heart, Lung, and Blood Institute (NHLBI) (NIH)
31
1
2
41
0.8

Study Details

Study Description

Brief Summary

RATIONALE: Giving low doses of 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 stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect).

PURPOSE: This phase I trial is studying the safety of donor umbilical cord blood transplant after fludarabine phosphate, cyclophosphamide, and total-body irradiation in treating patients with high-risk hematologic cancer (now closed).

The Phase II part of this trial is studying whether priming one of two UCB units with C3a facilitates engraftment of the treated unit.

Condition or Disease Intervention/Treatment Phase
  • Drug: cyclophosphamide
  • Drug: fludarabine phosphate
  • Radiation: Total body irradiation
  • Biological: Umbilical cord blood unit with C3a fragment
  • Biological: Unmanipulated UCB Unit
Phase 1/Phase 2

Detailed Description

OUTLINE:
  • Nonmyeloablative preparative regimen: Patients receive fludarabine phosphate IV over 1 hour on days -6 to -2 and cyclophosphamide IV over 2 hours on day -6. Patients then undergo total-body irradiation on day -1. Some patients also receive anti-thymocyte globulin IV every 12 hours on days -6, -5, and -4.

  • Umbilical cord blood (UCB) transplantation: Patients undergo unmanipulated UCB transplantation followed by complement 3a fragment primed UCB transplantation on day 0.

Treatment for graft-vs-host disease prophylaxis is also given.

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

Study Design

Study Type:
Interventional
Actual Enrollment :
31 participants
Allocation:
Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
MT2008-15: Transplantation of Unrelated Donor Umbilical Cord Blood in Patients With Hematological Malignancies Using a Nonmyeloablative Preparative Regimen and Priming With Complement 3a Fragment (C3a)
Study Start Date :
Mar 1, 2010
Actual Primary Completion Date :
Aug 1, 2012
Actual Study Completion Date :
Aug 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: Complement Fragment 3A - Small Cell Dose

Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation.

Drug: cyclophosphamide
50 mg/kg intravenously (IV) over 2 hours on Day -6.
Other Names:
  • Cytoxan
  • Drug: fludarabine phosphate
    40 mg/m^2 over 1 hour on Days -6 through -2.
    Other Names:
  • Fludara
  • Radiation: Total body irradiation
    200 cGy on Day -1

    Biological: Umbilical cord blood unit with C3a fragment
    On Day 0, the C3a primed UCB unit will be infused intravenously SECOND, within 30 minutes of the completion of the infusion of the unmanipulated UCB unit, through a central line without in-line filtration in a manner identical to the unmanipulated UCB unit.

    Biological: Unmanipulated UCB Unit
    On Day 0, the unmanipulated UCB unit will be infused FIRST through a central line without in-line filtration per institutional guidelines.

    Experimental: Complement Fragment A - Larger Cell Dose

    Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.

    Drug: cyclophosphamide
    50 mg/kg intravenously (IV) over 2 hours on Day -6.
    Other Names:
  • Cytoxan
  • Drug: fludarabine phosphate
    40 mg/m^2 over 1 hour on Days -6 through -2.
    Other Names:
  • Fludara
  • Radiation: Total body irradiation
    200 cGy on Day -1

    Biological: Umbilical cord blood unit with C3a fragment
    On Day 0, the C3a primed UCB unit will be infused intravenously SECOND, within 30 minutes of the completion of the infusion of the unmanipulated UCB unit, through a central line without in-line filtration in a manner identical to the unmanipulated UCB unit.

    Biological: Unmanipulated UCB Unit
    On Day 0, the unmanipulated UCB unit will be infused FIRST through a central line without in-line filtration per institutional guidelines.

    Outcome Measures

    Primary Outcome Measures

    1. Number of Patients With the Complement 3a (C3a) Unit Predominating [Day 180]

      Efficacy of the pre-incubation of one of two umbilical cord blood (UCB) units with C3a as part of a unrelated donor double UCB nonmyeloablative transplantation in patients with high-risk hematological malignancies.

    Secondary Outcome Measures

    1. Neutrophil Engraftment [Day 42]

      Achieving 500 neutrophils/uL by day 42.

    2. Donor Chimerism in Blood [Day 28]

      Percentage of donor DNA present in the peripheral blood

    3. Incidence of Grades II-IV Graft-vs-host Disease [Day 0 through Day 100]

      Development of graft-versus-host disease through day 100.

    4. Non-Relapse Mortality [Day 180]

      Deaths not due to relapse.

    5. Overall Survival [Day 360]

      Survival (alive) from transplantation to last follow-up.

    6. Bone Marrow Chimerism [Day 21]

      Percentage of donor DNA in the bone marrow.

    7. Chronic Graft-Versus-Host Disease [Day 360]

      Patients who developed chronic graft-versus-host disease.

    8. Relapse of Disease [Day 360]

      Patients who developed disease relapse after transplantation.

    9. Disease Progression [Day 360]

      Patients who developed disease progression after transplantation.

    10. Platelet Recovery [Day 180]

      Number of patients with >20,000 platelets/uL by day 180

    11. Donor Chimerism in Blood [Day 60]

      Percentage of donor DNA present in the peripheral blood

    12. Incidence of Grades III-IV Graft-vs-host Disease [0 to 100 days]

      Development of graft-versus-host disease by day 100.

    13. Non-relapse Mortality [Day 360]

      Deaths not due to relapse.

    14. Overall Survival at Day 720 [720 days]

      Survival (alive) from transplantation to last follow-up at day 720.

    15. Relapse of Disease [Day 720]

      Patients who developed disease relapse after transplantation.

    16. Disease Progression [Day 720]

      Patients who developed disease progression after transplantation.

    17. Donor Chimerism [Day 100]

      Percentage of donor DNA in the bone marrow.

    18. Donor Chimerism [Day 180]

      Percentage of donor DNA in the bone marrow.

    19. Donor Chimerism [Day 360]

      Percentage of donor DNA in the bone marrow.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Disease Criteria

    • Acute Leukemias: Must be in remission by morphology (<5% blasts). Note cytogenetic relapse or persistent disease without morphologic relapse is acceptable. Also a small percentage of blasts that is equivocal between marrow regeneration vs. early relapse are acceptable provided there are no associated cytogenetic markers consistent with relapse. (See exclusion criteria for more detailed definition)

    • Acute myeloid leukemia: high risk CR1 (as evidenced by preceding myelodysplastic syndrome (MDS), high risk cytogenetics such as those associated with MDS or complex karyotype, > 2 cycles to obtain complete remission (CR) or erythroblastic and megakaryocytic); second or greater CR.

    • Acute lymphoblastic leukemia/lymphoma: high risk CR1 as evidenced by high risk cytogenetics (e.g. t(9;22, t(1;19), t(4;11), other MLL rearrangements) or > 1 cycle to obtain CR; second or greater CR.

    • Burkitt's lymphoma in CR2 or subsequent CR

    • Natural Killer cell malignancies

    • Myeloproliferative syndromes/diseases: Chronic myelogenous leukemia (CML) in chronic or accelerated phase but patients must have failed or been intolerant to Imatinib mesylate. EXCLUDED: CML in refractory blast crisis, myelofibrosis, polycythemia vera, and essential thrombocytosis.

    • Myelodysplastic Syndrome: any subtype including refractory anemia (RA) if severe pancytopenia, high risk complex cytogenetics or International Prognostic Scoring System (IPSS) ≥ intermediate-2 (Int-2). Blasts must be less than 5%. If 5% or more requires therapy pre-transplant to reduce blast count to ≤5%. Patients who receive single agent 5-azacytidine, decitabine or immunomodulating drugs are eligible.

    • Large-cell lymphoma, Hodgkin's lymphoma and multiple myeloma: patients with chemotherapy sensitive disease that has failed or who are ineligible for an autologous transplant. Patients are eligible for umbilical cord blood (UCB) transplantation if there is no evidence of progressive disease by imaging modalities and/or biopsy. Persistent PET activity, though possibly related to lymphoma, IS NOT an exclusion criterion in the absence of computated tomography (CT) changes in size indicating progression. Large-cell and Hodgkin's lymphoma that is progressive on salvage therapy is NOT eligible. Patients with stable disease are eligible for transplantation if the largest residual nodal mass is < 5 cm (approximately). For patients who have responded to preceding therapy, the largest residual mass must represent a 50% reduction and be < 7.5 cm (approximately).

    • Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma, follicular lymphoma which have progressed after at least two prior therapies. Patients with bulky disease should be considered for debulking chemotherapy before transplant. Patients with refractory disease are eligible, unless has bulky disease and an estimated tumor doubling time of less than one month. Patients with stable disease are eligible for transplantation if the largest residual nodal mass is < 5 cm (approximately). For patients who have responded to preceding therapy, the largest residual mass must represent a 50% reduction and be < 7.5 cm (approximately).

    • Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are eligible after initial therapy if chemotherapy sensitive. Mantle-cell lymphoma that is progressive on salvage therapy is NOT eligible. Patients with stable disease are eligible for transplantation if the largest residual nodal mass is < 5 cm (approximately). For patients who have responded to preceding therapy, the largest residual mass must represent a 50% reduction and be < 7.5 cm (approximately).

    • Umbilical Cord Blood Graft Selection - Two UCB units will be compose the graft, and each unit must be a 4-6 HLA-A, B, DRB1 antigen match to each other, as well as a 4-6 antigen match to the recipient. The combined cryopreserved nucleated cell dose of the 2 units must be ≥ 3 X 107/kg with each unit having a minimum cell dose of 1.5 X 107/kg. UCB units will be selected according to a common umbilical cord blood graft selection algorithm

    • Performance Status - adequate performance status defined as Karnofsky score ≥ 60

    • Age 18 to 70 years of age; patients ≥ 70 but ≤ 75 years are eligible if the co-morbidity score is ≤ 2

    • Organ Function

    • Cardiac: Left ventricular ejection fraction > 35%; absence of decompensated congestive heart failure; absence of uncontrolled arrhythmia

    • Pulmonary: DLCO > 30% of predicted; absence of O2 requirements

    • Hepatic: ALT, AST, alkaline phosphatase and bilirubin < 5 x upper limit of normal

    • Renal: Creatinine ≤ 2 mg/dl (patients with a creatinine > 1.2 or history of renal dysfunction must have calculated glomerular filtration rate (GFR) > 40 mL/min/1.73m2)

    • If recent mold infection e.g. Aspergillus - must have minimum of 30 days of appropriate treatment before transplant and infection controlled and be cleared by Infectious Disease.

    • The following conditions must be met:

    • If prior myeloablative autologous transplant, must be > 3 months but ≤ 12 months from transplant OR have received at least 2 cycles of multi-agent or highly immunosuppressive chemotherapy (i.e. induction for acute leukemia) within the 3 months preceding this study. OR

    • If neither prior myeloablative autologous transplant ≤ 12 months from transplant nor have received at least 2 cycles of multi-agent or highly immunosuppressive chemotherapy (i.e. induction for acute leukemia) within the 3 months preceding this study, patients are eligible as long as they receive equine anti-thymocyte globulin as part of the conditioning regimen.

    Exclusion Criteria:
    • Patients who have an available, medically suitable, 5-6/6 HLA-A, B, DRB1 matched sibling donor

    • Patients who are eligible for autologous transplantation

    • Prior allogeneic transplant

    • Acquired or inherited bone marrow failure syndromes such as aplastic anemia and Fanconi anemia

    • Pregnant or breast feeding

    • Evidence of HIV infection or known HIV positive serology

    • Current uncontrolled serious infection

    • Active central nervous system malignancy

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Minnesota Medical Center - Fairview Minneapolis Minnesota United States 55455

    Sponsors and Collaborators

    • Masonic Cancer Center, University of Minnesota
    • National Heart, Lung, and Blood Institute (NHLBI)

    Investigators

    • Principal Investigator: Claudio G. Brunstein, MD, PhD, Masonic Cancer Center, University of Minnesota

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Masonic Cancer Center, University of Minnesota
    ClinicalTrials.gov Identifier:
    NCT00963872
    Other Study ID Numbers:
    • 2008UC097
    • MT2008-15
    • 0809M46361
    • RC1HL099447
    First Posted:
    Aug 24, 2009
    Last Update Posted:
    Dec 28, 2017
    Last Verified:
    Dec 1, 2017

    Study Results

    Participant Flow

    Recruitment Details Subjects were recruited at the time of clinic visit or hospitalization. Patients that were considered for umbilical cord transplant were approached with the study.
    Pre-assignment Detail Subjects that were eligible for umbilical cord transplant were considered for the study.
    Arm/Group Title Complement Fragment 3A - Small Cell Dose Complement Fragment A - Larger Cell Dose
    Arm/Group Description Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation. Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
    Period Title: Overall Study
    STARTED 25 6
    COMPLETED 24 5
    NOT COMPLETED 1 1

    Baseline Characteristics

    Arm/Group Title Complement Fragment 3A - Small Cell Dose Complement Fragment A - Larger Cell Dose Total
    Arm/Group Description Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation. Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose. Total of all reporting groups
    Overall Participants 25 6 31
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    19
    76%
    5
    83.3%
    24
    77.4%
    >=65 years
    6
    24%
    1
    16.7%
    7
    22.6%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    55
    (13.0)
    50
    (15.7)
    54
    (13.4)
    Sex: Female, Male (Count of Participants)
    Female
    9
    36%
    2
    33.3%
    11
    35.5%
    Male
    16
    64%
    4
    66.7%
    20
    64.5%
    Region of Enrollment (participants) [Number]
    United States
    25
    100%
    6
    100%
    31
    100%

    Outcome Measures

    1. Primary Outcome
    Title Number of Patients With the Complement 3a (C3a) Unit Predominating
    Description Efficacy of the pre-incubation of one of two umbilical cord blood (UCB) units with C3a as part of a unrelated donor double UCB nonmyeloablative transplantation in patients with high-risk hematological malignancies.
    Time Frame Day 180

    Outcome Measure Data

    Analysis Population Description
    Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.
    Arm/Group Title Complement Fragment 3A - Small Cell Dose Complement Fragment A - Larger Cell Dose
    Arm/Group Description Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation. Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
    Measure Participants 24 5
    Number [participants]
    9
    36%
    5
    83.3%
    2. Secondary Outcome
    Title Neutrophil Engraftment
    Description Achieving 500 neutrophils/uL by day 42.
    Time Frame Day 42

    Outcome Measure Data

    Analysis Population Description
    Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.
    Arm/Group Title Complement Fragment 3A - Small Cell Dose Complement Fragment A - Larger Cell Dose
    Arm/Group Description Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation. Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
    Measure Participants 24 5
    Number [participants]
    22
    88%
    5
    83.3%
    3. Secondary Outcome
    Title Donor Chimerism in Blood
    Description Percentage of donor DNA present in the peripheral blood
    Time Frame Day 28

    Outcome Measure Data

    Analysis Population Description
    Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.
    Arm/Group Title Complement Fragment 3A - Small Cell Dose Complement Fragment A - Larger Cell Dose
    Arm/Group Description Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation. Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
    Measure Participants 24 5
    Mean (Standard Deviation) [percentage of donor DNA]
    92
    (15)
    96
    (8)
    4. Secondary Outcome
    Title Incidence of Grades II-IV Graft-vs-host Disease
    Description Development of graft-versus-host disease through day 100.
    Time Frame Day 0 through Day 100

    Outcome Measure Data

    Analysis Population Description
    Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.
    Arm/Group Title Complement Fragment 3A - Small Cell Dose Complement Fragment A - Larger Cell Dose
    Arm/Group Description Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation. Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
    Measure Participants 24 5
    Number [participants]
    8
    32%
    1
    16.7%
    5. Secondary Outcome
    Title Non-Relapse Mortality
    Description Deaths not due to relapse.
    Time Frame Day 180

    Outcome Measure Data

    Analysis Population Description
    Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.
    Arm/Group Title Complement Fragment 3A - Small Cell Dose Complement Fragment A - Larger Cell Dose
    Arm/Group Description Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation. Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
    Measure Participants 24 5
    Number [participants]
    3
    12%
    0
    0%
    6. Secondary Outcome
    Title Overall Survival
    Description Survival (alive) from transplantation to last follow-up.
    Time Frame Day 360

    Outcome Measure Data

    Analysis Population Description
    Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.
    Arm/Group Title Complement Fragment 3A - Small Cell Dose Complement Fragment A - Larger Cell Dose
    Arm/Group Description Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation. Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
    Measure Participants 24 5
    Number [participants]
    14
    56%
    5
    83.3%
    7. Secondary Outcome
    Title Bone Marrow Chimerism
    Description Percentage of donor DNA in the bone marrow.
    Time Frame Day 21

    Outcome Measure Data

    Analysis Population Description
    Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.
    Arm/Group Title Complement Fragment 3A - Small Cell Dose Complement Fragment A - Larger Cell Dose
    Arm/Group Description Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation. Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
    Measure Participants 24 5
    Mean (Standard Deviation) [percentage of donor DNA]
    84
    (25)
    89
    (23)
    8. Secondary Outcome
    Title Chronic Graft-Versus-Host Disease
    Description Patients who developed chronic graft-versus-host disease.
    Time Frame Day 360

    Outcome Measure Data

    Analysis Population Description
    Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.
    Arm/Group Title Complement Fragment 3A - Small Cell Dose Complement Fragment A - Larger Cell Dose
    Arm/Group Description Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation. Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
    Measure Participants 24 5
    Number [participants]
    0
    0%
    0
    0%
    9. Secondary Outcome
    Title Relapse of Disease
    Description Patients who developed disease relapse after transplantation.
    Time Frame Day 360

    Outcome Measure Data

    Analysis Population Description
    Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.
    Arm/Group Title Complement Fragment 3A - Small Cell Dose Complement Fragment A - Larger Cell Dose
    Arm/Group Description Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation. Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
    Measure Participants 24 5
    Number [participants]
    10
    40%
    0
    0%
    10. Secondary Outcome
    Title Disease Progression
    Description Patients who developed disease progression after transplantation.
    Time Frame Day 360

    Outcome Measure Data

    Analysis Population Description
    Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.
    Arm/Group Title Complement Fragment 3A - Small Cell Dose Complement Fragment A - Larger Cell Dose
    Arm/Group Description Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation. Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
    Measure Participants 24 5
    Number [participants]
    0
    0%
    0
    0%
    11. Secondary Outcome
    Title Platelet Recovery
    Description Number of patients with >20,000 platelets/uL by day 180
    Time Frame Day 180

    Outcome Measure Data

    Analysis Population Description
    Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.
    Arm/Group Title Complement Fragment 3A - Small Cell Dose Complement Fragment A - Larger Cell Dose
    Arm/Group Description Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation. Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
    Measure Participants 24 5
    Number [participants]
    19
    76%
    5
    83.3%
    12. Secondary Outcome
    Title Donor Chimerism in Blood
    Description Percentage of donor DNA present in the peripheral blood
    Time Frame Day 60

    Outcome Measure Data

    Analysis Population Description
    Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.
    Arm/Group Title Complement Fragment 3A - Small Cell Dose Complement Fragment A - Larger Cell Dose
    Arm/Group Description Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation. Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
    Measure Participants 24 5
    Mean (Standard Deviation) [percentage of donor DNA]
    91
    (23)
    97
    (4)
    13. Secondary Outcome
    Title Incidence of Grades III-IV Graft-vs-host Disease
    Description Development of graft-versus-host disease by day 100.
    Time Frame 0 to 100 days

    Outcome Measure Data

    Analysis Population Description
    Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.
    Arm/Group Title Complement Fragment 3A - Small Cell Dose Complement Fragment A - Larger Cell Dose
    Arm/Group Description Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation. Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
    Measure Participants 24 5
    Number [participants]
    2
    8%
    0
    0%
    14. Secondary Outcome
    Title Non-relapse Mortality
    Description Deaths not due to relapse.
    Time Frame Day 360

    Outcome Measure Data

    Analysis Population Description
    Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.
    Arm/Group Title Complement Fragment 3A - Small Cell Dose Complement Fragment A - Larger Cell Dose
    Arm/Group Description Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation. Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
    Measure Participants 24 5
    Number [participants]
    3
    12%
    0
    0%
    15. Secondary Outcome
    Title Overall Survival at Day 720
    Description Survival (alive) from transplantation to last follow-up at day 720.
    Time Frame 720 days

    Outcome Measure Data

    Analysis Population Description
    Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.
    Arm/Group Title Complement Fragment 3A - Small Cell Dose Complement Fragment A - Larger Cell Dose
    Arm/Group Description Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation. Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
    Measure Participants 24 5
    Number [participants]
    13
    52%
    5
    83.3%
    16. Secondary Outcome
    Title Relapse of Disease
    Description Patients who developed disease relapse after transplantation.
    Time Frame Day 720

    Outcome Measure Data

    Analysis Population Description
    Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.
    Arm/Group Title Complement Fragment 3A - Small Cell Dose Complement Fragment A - Larger Cell Dose
    Arm/Group Description Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation. Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
    Measure Participants 24 5
    Number [participants]
    11
    44%
    1
    16.7%
    17. Secondary Outcome
    Title Disease Progression
    Description Patients who developed disease progression after transplantation.
    Time Frame Day 720

    Outcome Measure Data

    Analysis Population Description
    Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.
    Arm/Group Title Complement Fragment 3A - Small Cell Dose Complement Fragment A - Larger Cell Dose
    Arm/Group Description Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation. Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
    Measure Participants 24 5
    Number [participants]
    0
    0%
    0
    0%
    18. Secondary Outcome
    Title Donor Chimerism
    Description Percentage of donor DNA in the bone marrow.
    Time Frame Day 100

    Outcome Measure Data

    Analysis Population Description
    Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.
    Arm/Group Title Complement Fragment 3A - Small Cell Dose Complement Fragment A - Larger Cell Dose
    Arm/Group Description Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation. Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
    Measure Participants 24 5
    Mean (Standard Deviation) [percentage of donor DNA]
    90
    (22)
    94
    (19)
    19. Secondary Outcome
    Title Donor Chimerism
    Description Percentage of donor DNA in the bone marrow.
    Time Frame Day 180

    Outcome Measure Data

    Analysis Population Description
    Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.
    Arm/Group Title Complement Fragment 3A - Small Cell Dose Complement Fragment A - Larger Cell Dose
    Arm/Group Description Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation. Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
    Measure Participants 24 5
    Mean (Standard Deviation) [percentage of donor DNA]
    99
    (3)
    100
    (0)
    20. Secondary Outcome
    Title Donor Chimerism
    Description Percentage of donor DNA in the bone marrow.
    Time Frame Day 360

    Outcome Measure Data

    Analysis Population Description
    Two patients were unevaluable - one, because 1 bag of cord blood broke leaving only 1 cord available, and one subject never received the C3a.
    Arm/Group Title Complement Fragment 3A - Small Cell Dose Complement Fragment A - Larger Cell Dose
    Arm/Group Description Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation. Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
    Measure Participants 24 5
    Mean (Standard Deviation) [percentage of donor DNA]
    93
    (19)
    100
    (0)

    Adverse Events

    Time Frame 100 days after umbilical cord blood transplant
    Adverse Event Reporting Description
    Arm/Group Title Complement Fragment 3A - Small Cell Dose Complement Fragment A - Larger Cell Dose
    Arm/Group Description Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation. Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
    All Cause Mortality
    Complement Fragment 3A - Small Cell Dose Complement Fragment A - Larger Cell Dose
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Complement Fragment 3A - Small Cell Dose Complement Fragment A - Larger Cell Dose
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 21/24 (87.5%) 5/5 (100%)
    Blood and lymphatic system disorders
    Blood and lymphatic disorders- Other 10/24 (41.7%) 10 0/5 (0%) 0
    Leukocytosis 1/24 (4.2%) 1 0/5 (0%) 0
    Gastrointestinal disorders
    Diarrhea 1/24 (4.2%) 1 0/5 (0%) 0
    Nausea 1/24 (4.2%) 2 0/5 (0%) 0
    Pancreatitis 1/24 (4.2%) 1 0/5 (0%) 0
    Stomach pain 1/24 (4.2%) 1 0/5 (0%) 0
    Upper gastrointestinal hemorrhage 1/24 (4.2%) 1 0/5 (0%) 0
    Vomiting 1/24 (4.2%) 1 0/5 (0%) 0
    General disorders
    Death NOS 2/24 (8.3%) 2 0/5 (0%) 0
    Fever 5/24 (20.8%) 5 0/5 (0%) 0
    Infusion related reaction 0/24 (0%) 0 1/5 (20%) 1
    Infections and infestations
    Catheter related infection 1/24 (4.2%) 1 0/5 (0%) 0
    Lung infection 1/24 (4.2%) 1 1/5 (20%) 1
    Investigations
    Aspartate aminotransferase increased 0/24 (0%) 0 1/5 (20%) 1
    Nervous system disorders
    Peripheral sensory neuropathy 1/24 (4.2%) 1 0/5 (0%) 0
    Seizure 2/24 (8.3%) 2 0/5 (0%) 0
    Psychiatric disorders
    Confusion 2/24 (8.3%) 2 0/5 (0%) 0
    Renal and urinary disorders
    Hematuria 1/24 (4.2%) 1 0/5 (0%) 0
    Renal and urinary disorders- Other 1/24 (4.2%) 1 0/5 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Adult respiratory distress syndrome 1/24 (4.2%) 1 2/5 (40%) 2
    Bronchopulmonary hemorrhage 1/24 (4.2%) 1 0/5 (0%) 0
    Dyspnea 0/24 (0%) 0 1/5 (20%) 1
    Pleuritic plan 1/24 (4.2%) 1 0/5 (0%) 0
    Vascular disorders
    Thromboembolic event 0/24 (0%) 0 1/5 (20%) 1
    Other (Not Including Serious) Adverse Events
    Complement Fragment 3A - Small Cell Dose Complement Fragment A - Larger Cell Dose
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 24/24 (100%) 5/5 (100%)
    Blood and lymphatic system disorders
    Hypertension 24/24 (100%) 24 4/5 (80%) 4
    Cardiac disorders
    Sinus tachycardia 2/24 (8.3%) 2 1/5 (20%) 1
    Sinus bradycardia 7/24 (29.2%) 7 2/5 (40%) 2
    Nervous system disorders
    Neurologic disorder 4/24 (16.7%) 4 1/5 (20%) 1
    Skin and subcutaneous tissue disorders
    Rash 3/24 (12.5%) 3 0/5 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Claudio Brunstein
    Organization University of Minnesota
    Phone 612-625-3918
    Email bruns072@umn.edu
    Responsible Party:
    Masonic Cancer Center, University of Minnesota
    ClinicalTrials.gov Identifier:
    NCT00963872
    Other Study ID Numbers:
    • 2008UC097
    • MT2008-15
    • 0809M46361
    • RC1HL099447
    First Posted:
    Aug 24, 2009
    Last Update Posted:
    Dec 28, 2017
    Last Verified:
    Dec 1, 2017