Skip to main content
OpenTrials
Completed

NCT Number: NCT01093586

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

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 With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia in Remission 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 Blast Crisis Blastic Phase Chronic Myelogenous Leukemia Blood Protein Disorders Bone Marrow Diseases Burkitt Lymphoma Carcinogenesis Cardiovascular Diseases Cell Transformation, Neoplastic 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 Disease Chronic Myelomonocytic Leukemia Chronic Phase Chronic Myelogenous Leukemia Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Cutaneous B-cell Non-Hodgkin Lymphoma DNA Virus Infections Dendritic Cell Sarcoma, Interdigitating Disease Attributes Epstein-Barr Virus Infections Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Herpesviridae Infections Histiocytic Disorders, Malignant Histiocytosis Immune System Diseases Immunoproliferative Disorders Infections Juvenile Myelomonocytic Leukemia Leukemia Leukemia, B-Cell Leukemia, Erythroblastic, Acute Leukemia, Large Granular Lymphocytic Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Leukemia, Megakaryoblastic, Acute Leukemia, Monocytic, Acute Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid Leukemia, Myeloid, Acute Leukemia, Myeloid, Chronic-Phase Leukemia, Myelomonocytic, Chronic Leukemia, Myelomonocytic, Juvenile Leukemia, Prolymphocytic Leukemia, T-Cell Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, B-Cell, Marginal Zone Lymphoma, Extranodal NK-T-Cell Lymphoma, Follicular Lymphoma, Large B-Cell, Diffuse Lymphoma, Large-Cell, Anaplastic Lymphoma, Large-Cell, Immunoblastic Lymphoma, Mantle-Cell Lymphoma, Non-Hodgkin Lymphoma, T-Cell Lymphoma, T-Cell, Cutaneous Lymphoproliferative Disorders Mycosis Fungoides Myelodysplastic-Myeloproliferative Diseases Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable Myeloproliferative Disorders Neoplasms Neoplasms by Histologic Type Neoplasms, Plasma Cell Neoplastic Processes Nodal Marginal Zone B-cell Lymphoma Paraproteinemias Pathologic Processes Pathological Conditions, Signs and Symptoms Precursor Cell Lymphoblastic Leukemia-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 Sezary Syndrome 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 Tumor Virus Infections Vascular Diseases Virus Diseases Waldenstrom Macroglobulinemia de Novo Myelodysplastic Syndromes

Age range

12 year–64 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

About this study

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

  • 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.
  • 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).
  • To determine the probability of overall survival and disease free survival at one and two years.
  • To describe the incidence of disease recurrence at one and two years in patients post UCBT.
  • To describe the incidence of acute GVHD and chronic GVHD at 100 days and at one year, respectively.
  • To determine the incidence of day 100 and 180 treatment related mortality.
  • To determine the incidence of serious infectious complications in the first year after transplant.
  • To determine the incidence of donor-derived neutrophil and platelet recovery.
  • 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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Double-Unit Umbilical Cord Blood Transplantation

Procedure

Undergo transplantation

cytogenetic analysis

Other

Correlative studies

Bone Marrow Aspiration

Procedure

Correlative studies

fluorescence in situ hybridization

Other

Correlative studies

Other names: fluorescence in situ hybridization (FISH)

busulfan

Drug

Given orally

Other names: BSF, BU, Misulfan, Mitosan, Myeloleukon, Myelosan

Cyclophosphamide

Drug

Given IV

Other names: CPM, CTX, Cytoxan, Endoxan, Endoxana, Enduxan

anti-thymocyte globulin

Drug

Given IV

Other names: ATG, ATGAM, lymphocyte immune globulin, Thymoglobulin

methylprednisolone

Drug

Given IV

Other names: A-MethaPred, Depo-Medrol, Medrol, MePRDL, Solu-Medrol, Wyacort

cyclosporine

Drug

Given IV

Other names: 27-400, ciclosporin, cyclosporin, cyclosporin A, CYSP, Sandimmune

Mycophenolate mofetil

Drug

Given orally or IV

Other names: Cellcept, MMF

flow cytometry

Other

Correlative studies

allogeneic hematopoietic stem cell transplantation

Procedure

Undergo transplantation

Primary outcomes

  1. Overall Survival

    Time frame: On day +180

    Number of participants alive at 180 days post engraftment.

Secondary outcomes

  1. Hematologic Engraftment

    Time frame: On day +42

    Number of participants that were able to complete engraftment by day 42.

  2. Overall Survival

    Time frame: At 1 year

    Number of participants that were alive.

  3. Overall Survival

    Time frame: At 2 years

    Number of participants that were alive.

  4. Disease Free

    Time frame: At 1 year

    Number of participants that were disease free

  5. Disease Free

    Time frame: At 2 years

    Number of participants that were disease free

  6. Recurrence or Relapse

    Time frame: one year in patients post UCBT

    Number of subjects that had disease recurrence

  7. Recurrence or Relapse

    Time frame: two years post transplant

    Number of subjects that had disease recurrence

  8. Transplant Related Mortality

    Time frame: On day 100 post transplant

    Number of subjects that died because of transplant

  9. Transplant Related Mortality

    Time frame: On day 180 post transplant

    Number of subjects that died because of transplant

  10. Occurrence of Serious Infections

    Time frame: 1 year

    Number of participants that had infections

  11. Immune Reconstitution

    Time frame: Periodically for 2 years

    Immunodificency panel to see recovery of immune system. Number of participants that recovered.

  12. 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

  13. Incidence of Acute Graft-versus-host Disease (GVHD)

    Time frame: At 100 days

    Number of participants that had acute GVHD

  14. 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)

Sponsors and collaborators

Lead sponsor

Case Comprehensive Cancer Center

Other

Registry information

Official study title

Umbilical Cord Blood (UCB) Allogeneic Stem Cell Transplant for Hematologic Malignancies

Important dates

Study start
2007
Primary completion
2015
Study completion
2015
First posted
Mar 26, 2010
Registry last updated
Jan 23, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.