Myeloablative Umbilical Cord Blood Transplantation in Hematological Diseases
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ClinicalTrials.gov Identifier: NCT00309842 |
Recruitment Status :
Completed
First Posted : April 3, 2006
Results First Posted : September 10, 2020
Last Update Posted : September 10, 2020
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RATIONALE: Giving chemotherapy drugs, such as fludarabine and cyclophosphamide, and total-body irradiation before a donor umbilical cord blood stem cell transplant helps stop the growth of cancer cells and prepares the patient's bone marrow for the stem cells. When the healthy stem cells from a donor 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 cyclosporine and mycophenolate mofetil may stop this from happening.
PURPOSE: This phase II trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation works in treating patients who are undergoing an umbilical cord blood transplant for hematologic cancer.
Condition or disease | Intervention/treatment | Phase |
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Acute Myeloid Leukemia Acute Lymphocytic Leukemia Chronic Myelogenous Leukemia Myelofibrosis MDS Refractory Anemia Chronic Lymphocytic Leukemia Prolymphocytic Leukemia Non-Hodgkin's Lymphoma Leukemia Lymphoma Multiple Myeloma Myelodysplastic Syndromes | Biological: filgrastim Drug: cyclophosphamide Drug: cyclosporine Drug: fludarabine phosphate Drug: mycophenolate mofetil Procedure: umbilical cord blood transplantation Radiation: total-body irradiation | Phase 2 |
OBJECTIVES:
Primary
- Determine the 1-year survival of patients undergoing unrelated umbilical cord blood transplantation (UCBT) for hematologic malignancies treated with myeloablative preparative regimen comprising fludarabine, cyclophosphamide, and fractionated total-body irradiation.
Secondary
- Determine the incidence of transplant-related mortality at 6 months after UCBT.
- Evaluate the pattern of chimerism after double UCBT.
- Determine the incidence of neutrophil engraftment at day 42 after UCBT.
- Determine the incidence of platelet engraftment at 6 months after UCBT.
- Determine the incidence of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) at day 100 after UCBT.
- Determine the incidence of chronic GVHD at 1 year after UCBT.
- Determine the disease-free survival at 1 and 2 years after UCBT.
- Determine the incidence of relapse at 1 year after UCBT.
OUTLINE: This is a nonrandomized, open-label, multicenter study.
- Preparative Regimen: Patients receive fludarabine IV over 1 hour on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients also undergo total-body irradiation twice daily on days -4 to -1.
- Umbilical Cord Blood Transplantation (UCBT): Patients undergo 1 or 2 units of UCBT on day 0. Patients receive filgrastim (G-CSF) IV once daily beginning on day 1 and continuing until blood counts recover.
- Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV over 2 hours 2 or 3 times daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. Patients also receive mycophenolate mofetil IV or orally 2 or 3 times a day beginning on day -3 and continuing until day 30 or 7 days after engraftment in the absence of acute GVHD.
After completion of study treatment, patients are followed periodically for at least 5 years.
PROJECTED ACCRUAL: A total of 150 patients will be accrued for this study.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 213 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Transplantation of Unrelated Umbilical Cord Blood for Patients With Hematological Diseases With Cyclophosphamide/Fludarabine/Total Body Irradiation Myeloablative Preparative Regimen |
Actual Study Start Date : | July 28, 2005 |
Actual Primary Completion Date : | July 29, 2019 |
Actual Study Completion Date : | November 22, 2019 |

Arm | Intervention/treatment |
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Experimental: Unrelated UCBT for Blood Cancers
Patients undergoing unrelated umbilical cord blood transplantation (UCBT) for hematologic malignancies treated with myeloablative preparative regimen comprising fludarabine phosphate, mycophenolate mofetil, filgrastim, cyclophosphamide, cyclosporine and fractionated total-body irradiation.
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Biological: filgrastim
All patients will receive G-CSF 5 mcg/kg/day intravenously(IV) (dose rounded to vial size) based on the actual body weight IV beginning on day +1 after umbilical cord blood (UCB) infusion. G-CSF will be administered daily until the absolute neutrophil count (ANC) exceeds 2.5 x 10^9/L for three consecutive days.
Other Name: G-CSF Drug: cyclophosphamide Cyclophosphamide to be administered with high volume fluid flush and mesna (MT(S) 9006) at 10:00am, or per institutional routine, on days-7 and -6 after fludarabine. Cyclophosphamide 60mg/kg/day intravenous (IV) x 2 days, total dose 120 mg/kg (days -7 and -6) Dosing is calculated based on Actual BodyWeight (ABW) unless ABW > 30 kg above Ideal BodyWeight (IBW), in which case the dose should be computed using adjusted body weight.
Other Name: Cytoxan Drug: cyclosporine Patients will receive cyclosporine (CSA) therapy beginning on day -3 maintaining a level of > 200 ng/mL. For adults the initial dose will be 2.5 mg/kg intravenously (IV) over 2 hours every 12 hours. For children < 40 kg the initial dose will be 2.5 mg/kg IV over 2 hours every 8 hours.
Other Name: CSA Drug: fludarabine phosphate Fludarabine 25 mg/m2/day intravenously (IV) x 3 days, total dose 75 mg/m2 (days -8 to -6);
Other Name: Fludara Drug: mycophenolate mofetil All patients will begin mycophenolate mofetil (MMF) on day -3. Patients ≥ 40 kilograms will receive MMF at the dose of 3 grams/day divided into 2 or 3 doses (every 12 or 8 hours). Pediatric patient (<40 kilograms) will receive MMF at the dose of 15 mg/kg three times a day. Other Name: MMF Procedure: umbilical cord blood transplantation The product is infused via intravenous (IV) drip directly into the central line without a needle, pump or filter.
Other Name: UCBT Radiation: total-body irradiation The recommended TBI is 165 cGy given twice daily for a total dose of 1320 cGy (days -4 to -1).
Other Name: TBI |
- Number of Participants Who Were Alive at 1 Year Transplant Overall Survival [ Time Frame: at 1 year ]Number of patients alive at 1 year after transplant.
- Number of Participants Who Died Due to Transplant [ Time Frame: At Month 6 ]Determine the incidence of transplant-related mortality at 6 months after UCBT
- Number of Participants With Platelet Engraftment [ Time Frame: 6 months ]Determine the incidence of platelet engraftment (platelet recovery >50,000/uL) at 6 months after UCBT.
- Number of Participants With Neutrophil Engraftment [ Time Frame: Day 42 ]Determine the incidence of neutrophil engraftment at day 42 after UCBT Patients diagnosed with graft failure (failure of absolute neutrophil count ANC > 5 x 10^8/L of donor origin by day +42)
- Number of Participants With Acute Graft-Versus-Host Disease [ Time Frame: Day 100 ]
Determine the incidence of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) at day 100 after UCBT. Patients will be staged weekly between days 0 and 100 after transplantation using standard criteria following Przepiorka et al, 1995, Consensus Clinical Stage and Grade of Acute GVHD.
Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level.
- Number of Participants With Chronic Graft-Versus-Host Disease [ Time Frame: Year 1 ]
Determine the incidence of chronic GVHD at 1 year after UCBT. Patients will be staged weekly between days 0 and 100 after transplantation using standard criteria.
Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level.
- Percentage Chimerism on Day 21 [ Time Frame: Day 21 ]Chimerism studies will be performed on the bone marrow on days 21 and 100 and at 6 months, 1 year and 2 years. In cases of slow engraftment a bone marrow biopsy may be repeated on day +28.
- Percentage Chimerism on Day 100 [ Time Frame: Day 100 ]Chimerism studies will be performed on the bone marrow on days 21 and 100 and at 6 months, 1 year and 2 years. In cases of slow engraftment a bone marrow biopsy may be repeated on day +28.
- Percentage Chimerism at 6 Months [ Time Frame: Month 6 ]Chimerism studies will be performed on the bone marrow on days 21 and 100 and at 6 months, 1 year and 2 years. In cases of slow engraftment a bone marrow biopsy may be repeated on day +28.
- Percentage Chimerism at 1 Year [ Time Frame: 1 Year ]Chimerism studies will be performed on the bone marrow on days 21 and 100 and at 6 months, 1 year and 2 years. In cases of slow engraftment a bone marrow biopsy may be repeated on day +28.
- Percentage Chimerism at 2 Years [ Time Frame: 2 Years ]Chimerism studies will be performed on the bone marrow on days 21 and 100 and at 6 months, 1 year and 2 years. In cases of slow engraftment a bone marrow biopsy may be repeated on day +28.

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Ages Eligible for Study: | up to 55 Years (Child, Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Acute myeloid leukemia (AML): high risk CR1 (as evidenced by preceding myelodysplastic syndrome [MDS], high risk cytogenetics, ≥ 2 cycles to obtain complete remission [CR], erythroblastic or megakaryocytic leukemia; CR2+. All patients must be in CR as defined by hematological recovery, AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
- Very high risk pediatric patients with AML. Patients <21 years, however, are eligible with (M2 marrow) with < or = 25% blasts in marrow after having failed one or more cycles of chemotherapy. This group of patients will be analyzed separately.
- Acute lymphocytic leukemia (ALL): high risk CR1 [t(9;22), t (1:19), t(4;11) or other MLL rearrangements] hypodiploidy, or IKZF1 abnormalities), DNA index < 0.81, > 1 cycle to obtain CR or presence minimal residual disease (MRD). Patients in CR2+ are eligible. All patients must be in CR as defined by hematological recovery, AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
- Very high risk pediatric patients with ALL. patients <21 years are also considered high risk CR1 if they had M2 or M3 marrow at day 42 from the initiation of induction or M3 marrow at the end of induction. They are eligible once they achieved a complete remission
- Chronic myelogenous leukemia (CML) excluding refractory blast crisis. To be eligible in first chronic phase (CP1) patient must have failed or be intolerant to imatinib mesylate.
- Plasma Cell leukemia after initial therapy, who achieved at least a partial remission
- Advanced myelofibrosis
- Myelodysplasia (MDS) IPSS Int-2 or High risk (i.e. RAEB, RAEBt) or refractory anemia with severe pancytopenia or high risk cytogenetics. Blasts must be < 10% by a representative bone marrow aspirate morphology.
- Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma or follicular lymphoma are eligible if there was disease progression/relapse within 12 of achieving a partial or complete remission. Patients who had remissions lasting > 12 months, are eligible after at least two prior therapies. Patients with bulky disease (nodal mass greater than 5 cm) should be considered for debulking chemotherapy before transplant.
- Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are eligible after initial therapy in CR1+ or PR1+.
- Large cell NHL > CR2/> PR2. Patients in CR2/PR2 with initial short remission (<6 months) are eligible.
- Lymphoblastic lymphoma, Burkitt's lymphoma, and other high-grade NHL after initial therapy if stage III/IV in CR1/PR1 or after progression if stage I/II < 1 year.
- Multiple myeloma beyond PR2. Patients with chromosome 13 abnormalities, first response lasting less than 6 months, or β-2 microglobulin > 3 mg/L, may be considered for this protocol after initial therapy.
- Recipients must have a Karnofsky score (adults) ≥ 80 % or Lansky score ≥ 50% (pediatrics), and proper organ function.
Exclusion Criteria
- Active infection at time of transplantation
- History of human immunodeficiency virus (HIV) infection
- Pregnant or breast feeding.
- Chemotherapy refractory large cell and high grade NHL
- If < or = 18 years old, prior myeloablative transplant within the last 6 months. If >18 years old prior myeloablative allotransplant or autologous transplant
- Extensive prior therapy including > 12 months alkylator therapy or > 6 months alkylator therapy with extensive radiation.
- Patients who have received Y-90 ibritumomab (Zevalin) or I-131 tostumomab (Bexxar), as part of their salvage therapy.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00309842
United States, Minnesota | |
Masonic Cancer Center at University of Minnesota | |
Minneapolis, Minnesota, United States, 55455 | |
United States, Washington | |
Fred Hutchinson Cancer Research Center | |
Seattle, Washington, United States, 98109 |
Study Chair: | Claudio G. Brunstein, MD, PhD | Masonic Cancer Center, University of Minnesota |
Documents provided by Masonic Cancer Center, University of Minnesota:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Masonic Cancer Center, University of Minnesota |
ClinicalTrials.gov Identifier: | NCT00309842 |
Other Study ID Numbers: |
2005LS043 UMN-MT2005-10 ( Other Identifier: Blood and Marrow Transplantation Program ) UMN-0507M71475 ( Other Identifier: IRB, University of Minnesota ) |
First Posted: | April 3, 2006 Key Record Dates |
Results First Posted: | September 10, 2020 |
Last Update Posted: | September 10, 2020 |
Last Verified: | September 2020 |
blastic phase chronic myelogenous leukemia primary myelofibrosis chronic myelomonocytic leukemia myelodysplastic syndromes juvenile myelomonocytic leukemia recurrent adult Burkitt lymphoma recurrent adult immunoblastic large cell lymphoma recurrent lymphoblastic lymphoma recurrent childhood acute myeloid leukemia recurrent childhood large cell lymphoma recurrent follicular lymphoma recurrent marginal zone lymphoma recurrent small lymphocytic lymphoma refractory chronic lymphocytic leukemia |
refractory multiple myeloma chronic myelogenous leukemia secondary acute myeloid leukemia secondary myelodysplastic syndromes multiple myeloma adult lymphoblastic lymphoma refractory anemia with excess blasts refractory anemia Burkitt lymphoma childhood large cell lymphoma adult Burkitt lymphoma mantle cell lymphoma childhood lymphoblastic lymphoma childhood myelodysplastic syndromes |
Lymphoma Leukemia Leukemia, Myeloid Multiple Myeloma Neoplasms, Plasma Cell Leukemia, Myeloid, Acute Preleukemia Leukemia, Lymphoid Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Myelogenous, Chronic, BCR-ABL Positive Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Prolymphocytic Anemia Myelodysplastic Syndromes Primary Myelofibrosis |
Anemia, Refractory Hematologic Diseases Syndrome Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Disease Pathologic Processes Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias |