Myeloablative Umbilical Cord Blood Transplantation in Hematological Diseases
Transplantation of Unrelated Umbilical Cord Blood for Patients With Hematological Diseases With Cyclophosphamide/Fludarabine/Total Body Irradiation Myeloablative Preparative Regimen
3 other identifiers
interventional
213
1 country
2
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jul 2005
Longer than P75 for phase_2
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 28, 2005
CompletedFirst Submitted
Initial submission to the registry
March 29, 2006
CompletedFirst Posted
Study publicly available on registry
April 3, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 29, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
November 22, 2019
CompletedResults Posted
Study results publicly available
September 10, 2020
CompletedSeptember 10, 2020
September 1, 2020
14 years
March 29, 2006
August 19, 2020
September 9, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Participants Who Were Alive at 1 Year Transplant Overall Survival
Number of patients alive at 1 year after transplant.
at 1 year
Secondary Outcomes (10)
Number of Participants Who Died Due to Transplant
At Month 6
Number of Participants With Platelet Engraftment
6 months
Number of Participants With Neutrophil Engraftment
Day 42
Number of Participants With Acute Graft-Versus-Host Disease
Day 100
Number of Participants With Chronic Graft-Versus-Host Disease
Year 1
- +5 more secondary outcomes
Study Arms (1)
Unrelated UCBT for Blood Cancers
EXPERIMENTALPatients 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.
Interventions
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.
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.
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.
Fludarabine 25 mg/m2/day intravenously (IV) x 3 days, total dose 75 mg/m2 (days -8 to -6);
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.
The product is infused via intravenous (IV) drip directly into the central line without a needle, pump or filter.
The recommended TBI is 165 cGy given twice daily for a total dose of 1320 cGy (days -4 to -1).
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, 55455, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109, United States
Related Publications (2)
Verneris MR, Brunstein CG, Barker J, MacMillan ML, DeFor T, McKenna DH, Burke MJ, Blazar BR, Miller JS, McGlave PB, Weisdorf DJ, Wagner JE. Relapse risk after umbilical cord blood transplantation: enhanced graft-versus-leukemia effect in recipients of 2 units. Blood. 2009 Nov 5;114(19):4293-9. doi: 10.1182/blood-2009-05-220525. Epub 2009 Aug 25.
PMID: 19706886RESULTMacMillan ML, Weisdorf DJ, Brunstein CG, Cao Q, DeFor TE, Verneris MR, Blazar BR, Wagner JE. Acute graft-versus-host disease after unrelated donor umbilical cord blood transplantation: analysis of risk factors. Blood. 2009 Mar 12;113(11):2410-5. doi: 10.1182/blood-2008-07-163238. Epub 2008 Nov 7.
PMID: 18997171DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr.Claudio G. Brunstein MD, PhD
- Organization
- Masonic Cancer Center, University of Minnesota
Study Officials
- STUDY CHAIR
Claudio G. Brunstein, MD, PhD
Masonic Cancer Center, University of Minnesota
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 29, 2006
First Posted
April 3, 2006
Study Start
July 28, 2005
Primary Completion
July 29, 2019
Study Completion
November 22, 2019
Last Updated
September 10, 2020
Results First Posted
September 10, 2020
Record last verified: 2020-09