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Donor Umbilical Cord Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies

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ClinicalTrials.gov Identifier: NCT01093586
Recruitment Status : Completed
First Posted : March 26, 2010
Results First Posted : January 4, 2019
Last Update Posted : January 23, 2019
Sponsor:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE March 24, 2010
First Posted Date  ICMJE March 26, 2010
Results First Submitted Date  ICMJE December 13, 2018
Results First Posted Date  ICMJE January 4, 2019
Last Update Posted Date January 23, 2019
Study Start Date  ICMJE September 2007
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 13, 2018)
Overall Survival [ Time Frame: On day +180 ]
Number of participants alive at 180 days post engraftment.
Original Primary Outcome Measures  ICMJE
 (submitted: March 25, 2010)
Overall Survival [ Time Frame: On day +180 ]
Change History Complete list of historical versions of study NCT01093586 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 3, 2019)
  • Hematologic Engraftment [ Time Frame: On day +42 ]
    Number of participants that were able to complete engraftment by day 42.
  • Overall Survival [ Time Frame: At 1 year ]
    Number of participants that were alive.
  • Overall Survival [ Time Frame: At 2 years ]
    Number of participants that were alive.
  • Disease Free [ Time Frame: At 1 year ]
    Number of participants that were disease free
  • Disease Free [ Time Frame: At 2 years ]
    Number of participants that were disease free
  • Recurrence or Relapse [ Time Frame: one year in patients post UCBT ]
    Number of subjects that had disease recurrence
  • Recurrence or Relapse [ Time Frame: two years post transplant ]
    Number of subjects that had disease recurrence
  • Transplant Related Mortality [ Time Frame: On day 100 post transplant ]
    Number of subjects that died because of transplant
  • Transplant Related Mortality [ Time Frame: On day 180 post transplant ]
    Number of subjects that died because of transplant
  • Occurrence of Serious Infections [ Time Frame: 1 year ]
    Number of participants that had infections
  • Immune Reconstitution [ Time Frame: Periodically for 2 years ]
    Immunodificency panel to see recovery of immune system. Number of participants that recovered.
  • Toxicity Related to UCB Transplantation and Cytoreduction as Assessed by CTC v3.0 [ Time Frame: by day +42 ]
    Number of participants that experienced toxicity related to the transplant
  • Incidence of Acute Graft-versus-host Disease (GVHD) [ Time Frame: At 100 days ]
    Number of participants that had acute GVHD
  • Incidence of Chronic GVHD [ Time Frame: At 1 year ]
    Number of participants that have chronic GVHD. Chronic GVHD will be diagnosed and graded on clinical and histological criteria from the Center for International Blood and Marrow Transplant Research (CIBMTR)
Original Secondary Outcome Measures  ICMJE
 (submitted: March 25, 2010)
  • Hematologic Engraftment [ Time Frame: On day +42 ]
  • Disease-free and overall survival [ Time Frame: At 1 and 2 years ]
  • Duration of response [ Time Frame: one and two years ]
  • Transplant Related Mortality [ Time Frame: On day 100 and 180 ]
  • Recurrence or Relapse [ Time Frame: one and two years in patients post UCBT ]
  • Occurrence of Serious Infections [ Time Frame: 1 year ]
  • Immune Reconstitution [ Time Frame: Periodically for 2 years ]
  • Toxicity Related to UCB Transplantation and Cytoreduction as Assessed by CTC v3.0 [ Time Frame: three consecutive measurements on different days by day +42 ]
  • Incidence of Acute Graft-versus-host Disease (GVHD) [ Time Frame: At 100 days ]
  • Incidence of Chronic GVHD [ Time Frame: At 1 year ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Donor Umbilical Cord Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
Official Title  ICMJE Umbilical Cord Blood (UCB) Allogeneic Stem Cell Transplant for Hematologic Malignancies
Brief Summary

RATIONALE: Giving chemotherapy before a donor umbilical cord blood transplant (UCBT) helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the stem cells from an unrelated donor, that do not exactly match the patient's blood, are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving antithymocyte globulin before transplant and cyclosporine and mycophenolate mofetil after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well donor umbilical cord blood stem cell transplant works in treating patients with hematologic malignancies.

Detailed Description

PRIMARY OBJECTIVES:

1. To establish the day +180 overall survival after a myeloablative unrelated double unit UCBT in a single institution setting.

SECONDARY OBJECTIVES:

  1. To determine the rates of hematologic and immune reconstitution in patients with high risk hematologic malignancies, who are undergoing myeloablative chemotherapy followed by infusion of double unit UCBT.
  2. To determine the contribution of each umbilical cord unit to immune reconstitution with a focus on both initial (day +21 BM, and +28 PB) and sustained engraftment (day +100 BM; PB at +14, +21, +28, +35, +42, +60, +100, +180, +1 and 2 years).
  3. To determine the probability of overall survival and disease free survival at one and two years.
  4. To describe the incidence of disease recurrence at one and two years in patients post UCBT.
  5. To describe the incidence of acute GVHD and chronic GVHD at 100 days and at one year, respectively.
  6. To determine the incidence of day 100 and 180 treatment related mortality.
  7. To determine the incidence of serious infectious complications in the first year after transplant.
  8. To determine the incidence of donor-derived neutrophil and platelet recovery.
  9. To determine the incidence of secondary lymphoproliferative diseases following transplantation with umbilical cord blood.

OUTLINE:

PREPARATIVE REGIMEN: Patients receive oral busulfan every 6 hours on days -8 to -5, cyclophosphamide IV on days -4 to -3, and anti-thymocyte globulin or methylprednisolone IV on days -3 to -1.

TRANSPLANTATION: Patients undergo double-unit umbilical cord blood allogeneic stem cell transplantation on day 0.

GRAFT-VS-HOST DISEASE PROPHYLAXIS: Beginning on day -2, patients receive cyclosporine IV and taper beginning on day 100. Patients also receive mycophenolate mofetil IV or orally every 8 hours on days -3 to 45. After completion of study treatment, patients are followed periodically.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome
  • Adult Acute Lymphoblastic Leukemia in Remission
  • Adult Acute Megakaryoblastic Leukemia (M7)
  • Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
  • Adult Acute Monoblastic Leukemia (M5a)
  • Adult Acute Monocytic Leukemia (M5b)
  • Adult Acute Myeloid Leukemia in Remission
  • Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
  • Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
  • Adult Erythroleukemia (M6a)
  • Adult Nasal Type Extranodal NK/T-cell Lymphoma
  • Adult Pure Erythroid Leukemia (M6b)
  • B-cell Adult Acute Lymphoblastic Leukemia
  • B-cell Childhood Acute Lymphoblastic Leukemia
  • Blastic Phase Chronic Myelogenous Leukemia
  • Burkitt Lymphoma
  • Childhood Acute Erythroleukemia (M6)
  • Childhood Acute Lymphoblastic Leukemia in Remission
  • Childhood Acute Megakaryocytic Leukemia (M7)
  • Childhood Acute Minimally Differentiated Myeloid Leukemia (M0)
  • Childhood Acute Monoblastic Leukemia (M5a)
  • Childhood Acute Monocytic Leukemia (M5b)
  • Childhood Acute Myeloid Leukemia in Remission
  • Childhood Chronic Myelogenous Leukemia
  • Childhood Diffuse Large Cell Lymphoma
  • Childhood Immunoblastic Large Cell Lymphoma
  • Childhood Myelodysplastic Syndromes
  • Childhood Nasal Type Extranodal NK/T-cell Lymphoma
  • Chronic Myelomonocytic Leukemia
  • Chronic Phase Chronic Myelogenous Leukemia
  • Cutaneous B-cell Non-Hodgkin Lymphoma
  • de Novo Myelodysplastic Syndromes
  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • Juvenile Myelomonocytic Leukemia
  • Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
  • Nodal Marginal Zone B-cell Lymphoma
  • Previously Treated Myelodysplastic Syndromes
  • Prolymphocytic Leukemia
  • Recurrent Adult Acute Lymphoblastic Leukemia
  • Recurrent Adult Acute Myeloid Leukemia
  • Recurrent Adult Burkitt Lymphoma
  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Recurrent Adult Diffuse Mixed Cell Lymphoma
  • Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
  • Recurrent Adult Grade III Lymphomatoid Granulomatosis
  • Recurrent Adult Immunoblastic Large Cell Lymphoma
  • Recurrent Adult Lymphoblastic Lymphoma
  • Recurrent Childhood Acute Lymphoblastic Leukemia
  • Recurrent Childhood Acute Myeloid Leukemia
  • Recurrent Childhood Anaplastic Large Cell Lymphoma
  • Recurrent Childhood Grade III Lymphomatoid Granulomatosis
  • Recurrent Childhood Large Cell Lymphoma
  • Recurrent Childhood Lymphoblastic Lymphoma
  • Recurrent Childhood Small Noncleaved Cell Lymphoma
  • Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
  • Recurrent Grade 1 Follicular Lymphoma
  • Recurrent Grade 2 Follicular Lymphoma
  • Recurrent Grade 3 Follicular Lymphoma
  • Recurrent Mantle Cell Lymphoma
  • Recurrent Marginal Zone Lymphoma
  • Recurrent Mycosis Fungoides/Sezary Syndrome
  • Recurrent Small Lymphocytic Lymphoma
  • Refractory Chronic Lymphocytic Leukemia
  • Relapsing Chronic Myelogenous Leukemia
  • Secondary Acute Myeloid Leukemia
  • Secondary Myelodysplastic Syndromes
  • Secondary Myelofibrosis
  • Splenic Marginal Zone Lymphoma
  • Stage I Chronic Lymphocytic Leukemia
  • Stage II Chronic Lymphocytic Leukemia
  • Stage III Chronic Lymphocytic Leukemia
  • Stage IV Chronic Lymphocytic Leukemia
  • T-cell Adult Acute Lymphoblastic Leukemia
  • T-cell Childhood Acute Lymphoblastic Leukemia
  • T-cell Large Granular Lymphocyte Leukemia
  • Waldenstrom Macroglobulinemia
Intervention  ICMJE
  • Procedure: double-unit umbilical cord blood transplantation
    Undergo transplantation
  • Other: cytogenetic analysis
    Correlative studies
  • Procedure: bone marrow aspiration
    Correlative studies
  • Other: fluorescence in situ hybridization
    Correlative studies
    Other Name: fluorescence in situ hybridization (FISH)
  • Drug: busulfan
    Given orally
    Other Names:
    • BSF
    • BU
    • Misulfan
    • Mitosan
    • Myeloleukon
    • Myelosan
  • Drug: cyclophosphamide
    Given IV
    Other Names:
    • CPM
    • CTX
    • Cytoxan
    • Endoxan
    • Endoxana
    • Enduxan
  • Drug: anti-thymocyte globulin
    Given IV
    Other Names:
    • ATG
    • ATGAM
    • lymphocyte immune globulin
    • Thymoglobulin
  • Drug: methylprednisolone
    Given IV
    Other Names:
    • A-MethaPred
    • Depo-Medrol
    • Medrol
    • MePRDL
    • Solu-Medrol
    • Wyacort
  • Drug: cyclosporine
    Given IV
    Other Names:
    • 27-400
    • ciclosporin
    • cyclosporin
    • cyclosporin A
    • CYSP
    • Sandimmune
  • Drug: mycophenolate mofetil
    Given orally or IV
    Other Names:
    • Cellcept
    • MMF
  • Other: flow cytometry
    Correlative studies
  • Procedure: allogeneic hematopoietic stem cell transplantation
    Undergo transplantation
Study Arms  ICMJE Experimental: Arm I
PREPARATIVE REGIMEN: Patients receive oral busulfan on days -8 to -5, cyclophosphamide IV on days -4 to -3, and anti-thymocyte globulin or methylprednisolone IV on days -3 to -1. TRANSPLANTATION: Patients undergo a double-unit umbilical cord blood allogeneic stem cell transplantation on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Beginning on day -2, patients receive cyclosporine IV and taper beginning on day 100. Patients also receive mycophenolate mofetil IV or orally on days -3 to 45.
Interventions:
  • Procedure: double-unit umbilical cord blood transplantation
  • Other: cytogenetic analysis
  • Procedure: bone marrow aspiration
  • Other: fluorescence in situ hybridization
  • Drug: busulfan
  • Drug: cyclophosphamide
  • Drug: anti-thymocyte globulin
  • Drug: methylprednisolone
  • Drug: cyclosporine
  • Drug: mycophenolate mofetil
  • Other: flow cytometry
  • Procedure: allogeneic hematopoietic stem cell transplantation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 18, 2015)
14
Original Estimated Enrollment  ICMJE
 (submitted: March 25, 2010)
47
Actual Study Completion Date  ICMJE December 2015
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients will be diagnosed with one of the following hematological malignancies: acute myelogenous leukemia (AML), acute lymphoblastic leukemia, non-Hodgkin's lymphoma, myelodysplastic syndrome (MDS), chronic myelogenous leukemia (CML), and myeloproliferative and lymphoproliferative disorders
  • AML--First remission (CR1) with high risk features including a known prior diagnosis of myelodysplasia (MDS); therapy related AML; white cell count at presentation > 100,000; presence of extramedullary leukemia at diagnosis; unfavorable AML subtype (M0, M5-M7); poor cytogenetic markers (abnormalities of chromosome 5, 7 or 8, 11q23, Philadelphia chromosome, complex karyotype)
  • AML--Second remission (CR2) or subsequent remission
  • AML--Relapse/Persistent Disease with < 20% bone marrow blasts
  • ALL--First remission (CR1) at high risk for relapse as defined by: B cell ALL white blood cell count (WBC) at presentation > 30,000 (T cell ALL WBC > 100,000); presence of high-risk cytogenetic abnormality such as t(9;22), t(1;19), t(4;11) or other MLL rearrangements (11q23), t(8;14)
  • ALL--Second remission (CR2) or subsequent remission
  • ALL--Relapse/Persistent Disease with < 20% bone marrow blasts
  • Non-Hodgkin Lymphoma--Induction failure or relapse and sensitive to most recent chemotherapy
  • MDS--Low or Intermediate-1 International Prognostic Scoring System (IPSS) score with: life-threatening cytopenia(s); and/or red cell or platelet transfusion dependence
  • MDS--ANC < 500, recurrent infections, PRBC transfusions > 2 units/month, poor risk cytogenetics, platelet transfusion dependence
  • MDS--Intermediate-2 or High IPSS score
  • CML--Chronic phase I (CP1) and resistant to or intolerant of tyrosine kinase inhibitors (i.e. imatinib, dasatinib, etc.)
  • CML--CP2 or subsequent chronic phase, including chronic phase achieved after induction therapy for blast crisis
  • Myeloproliferative and lymphoproliferative disorders--eligibility to be determined by a consensus of the physicians on the Case Comprehensive Cancer Center Leukemia/Lymphoma Multidisciplinary Committee
  • Myeloproliferative and lymphoproliferative disorders--must have evidence of disease acceleration to be a candidate for umbilical cord blood transplant; myeloproliferative disorders eligible for transplant include chronic myelomonocytic leukemia (CMML) with high IPSS score and myelofibrosis
  • Myeloproliferative and lymphoproliferative disorders--potential lymphoproliferative disorders eligible for transplant include chronic lymphocytic leukemia, prolymphocytic leukemia, and large granular lymphocytic leukemia
  • Good performance status: Karnofsky >= 70 % or ECOG 0-1
  • Calculated creatinine clearance >= 60 mL/min, or measured creatinine clearance >= 60 mL/min (by 24-hour urine collection) if creatinine >= 1.5 or history of renal dysfunction
  • Hepatic Transaminases < 4 x upper limit normal (ULN); total bilirubin < 2.5 mg/dL, unless the patient has a history of benign congenital hyperbilirubinemia (Gilbert's syndrome)
  • Normal cardiac function by echocardiogram or radionuclide scan, (left ventricular ejection fraction > 45%); if the left ventricular ejection fraction is between 40-50%, clearance by an adult cardiologist is required
  • Pulmonary function tests demonstrating FEV1 > 60% of predicted for age
  • Adults must have a DLCOva > 60% normal
  • For patients unable to complete pulmonary function tests clearance by an adult pulmonologist is required
  • Patients will be eligible for the clinical trial under the following conditions: they do NOT have an HLA-A/B/DR B1 identical RELATED bone marrow donor; they do NOT have a 6/6 HLA-identical matched unrelated adult donor; OR a matched related donor transplant is not in the best interest of the patient (i.e., patient's condition precludes waiting on the donor, too much time to prepare the donor, the donor is ineligible due to medical reasons, or in the case of high risk disease a related donor is not appropriated (syngeneic transplant); the decision must be agreed upon by the consensus of physicians on the Case Comprehensive Cancer Center Leukemia/Lymphoma Multidisciplinary Committee; OR their condition precludes waiting to search and find a donor in the National Marrow Donor Registry

Exclusion Criteria:

  • Female patients who are pregnant or breast-feeding
  • HIV or HTLV-1 positivity
  • Any leukemia with a morphologic relapse or persistent disease in the BM with >= 20% blasts (cytogenetic relapse without morphologic evidence of relapse, or cytogenetic persistent disease is acceptable)
  • Active extramedullary leukemia, including CNS disease
  • Prior hematopoietic stem cell transplant (autologous or allogeneic)
  • Uncontrolled infection
  • Patient has an identical related bone marrow donor or a 6/6 HLA-identical matched unrelated donor
  • Any patient who is unable to provide informed consent or comply with the requirements of the protocol
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years to 64 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01093586
Other Study ID Numbers  ICMJE CASE3Z07
NCI-2009-01319 ( Other Identifier: NCI/CTRP )
CASE3Z07 ( Other Identifier: Case Comprehensive Cancer Center )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Case Comprehensive Cancer Center
Study Sponsor  ICMJE Case Comprehensive Cancer Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Brenda Cooper, MD Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
PRS Account Case Comprehensive Cancer Center
Verification Date January 2019

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