Myeloablative Umbilical Cord Blood Transplantation in Hematological Diseases

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Masonic Cancer Center, University of Minnesota
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00309842
First received: March 29, 2006
Last updated: July 8, 2014
Last verified: July 2014
  Purpose

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 Intervention Phase
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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Overall survival [ Time Frame: at 1 year ] [ Designated as safety issue: No ]
    Number of patients alive at 1 year after transplant.


Secondary Outcome Measures:
  • Patients Who Died Due to Transplant [ Time Frame: At Month 6 ] [ Designated as safety issue: Yes ]
    Determine the incidence of transplant-related mortality at 6 months after UCBT

  • Chimerism [ Time Frame: Day 21, Day 100, Month 6, 1 Year, 2 Years ] [ Designated as safety issue: No ]
    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 BM biopsy may be repeated on day +28.

  • Neutrophil Engraftment [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
    Determine the incidence of neutrophil engraftment at day 42 after UCBT -Patients diagnosed with graft failure (failure of ANC > 5 x 108/L of donor origin by day +42)

  • Platelet Engraftment [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    Determine the incidence of platelet engraftment at 6 months after UCBT.

  • Acute Graft-Versus-Host Disease [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]

    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.

    Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level.


  • Number of Patients with Chronic Graft-Versus-Host Disease [ Time Frame: Year 1 ] [ Designated as safety issue: Yes ]

    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.



Estimated Enrollment: 150
Study Start Date: July 2005
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00309842

Contacts
Contact: Claudio G. Brunstein, M.D. 612-625-3918 bruns072@umn.edu

Locations
United States, Minnesota
Masonic Cancer Center at University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Clinical Trials Office - Masonic Cancer Center at University o    612-624-2620      
United States, Washington
Fred Hutchinson Cancer Research Center Terminated
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Study Chair: Claudio G. Brunstein, MD, PhD Masonic Cancer Center, University of Minnesota
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00309842     History of Changes
Other Study ID Numbers: 2005LS043, UMN-MT2005-10, UMN-0507M71475
Study First Received: March 29, 2006
Last Updated: July 8, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:
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

Additional relevant MeSH terms:
Anemia
Anemia, Refractory
Hematologic Diseases
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia, Prolymphocytic
Lymphoma
Lymphoma, Non-Hodgkin
Multiple Myeloma
Myelodysplastic Syndromes
Neoplasms, Plasma Cell
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Preleukemia
Primary Myelofibrosis
Syndrome
Blood Protein Disorders
Bone Marrow Diseases
Cardiovascular Diseases
Disease
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders

ClinicalTrials.gov processed this record on October 29, 2014