Non-Myeloablative Conditioning for Unrelated Donor Umbilical Cord Blood Transplant
Transplantation of Unrelated Donor Umbilical Cord Blood in Patients With Hematological Malignancies Using a Non-Myeloablative Preparative Regimen
3 other identifiers
interventional
295
1 country
1
Brief Summary
RATIONALE: Drugs used in chemotherapy, such as fludarabine and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill cancer cells. An umbilical cord blood transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving sirolimus and mycophenolate mofetil after the transplant may stop this from happening. PURPOSE: This phase II trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation followed by an umbilical cord blood transplant, sirolimus, and mycophenolate mofetil works in treating patients with 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 Jun 2005
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 1, 2005
CompletedFirst Submitted
Initial submission to the registry
March 21, 2006
CompletedFirst Posted
Study publicly available on registry
March 22, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 12, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
December 12, 2019
CompletedResults Posted
Study results publicly available
November 2, 2020
CompletedNovember 19, 2020
October 1, 2020
14.5 years
March 21, 2006
October 8, 2020
October 30, 2020
Conditions
Outcome Measures
Primary Outcomes (2)
Number of Participants Who Were Alive at 1 Year Post Transplant
Overall Survival - Number of patients alive at 1 year post transplant
1 Year
Number of Participants Who Were Alive at 2 Years Post Transplant
Overall Survival - Number of patients alive at 2 years post transplant
2 Years
Secondary Outcomes (13)
Number of Participants Who Were Dead at 6 Months After Study Completion
Month 6
Percentage of Donor Chimerism at 21 Days
21 days
Percentage of Donor Chimerism at 100 Days
100 days
Percentage of Donor Chimerism at 180 Days
180 Days
Percentage of Donor Chimerism at 365 Days
365 days
- +8 more secondary outcomes
Study Arms (6)
Arm 1-Previous Autologous Transplant
ACTIVE COMPARATORArm 1 - hematologic malignancy patients who have received a previous autologous transplant or ≥ 2 cycle of multiagent chemotherapy within the last 3 months previous to umbilical cord blood transplant (UCBT). Conditioning Fludarabine dose of 40 mg/m2/day x 5, cyclophosphamide and total body irradiation without anti-thymocyte globulin followed by umbilical cord blood transplantation, and peri-transplant Mycophenolate Mofetil and Sirolimus.
Arm 2 - No Prior Autologous Transplant
ACTIVE COMPARATORArm 2 - hematologic malignancy patients who have not been treated with prior autologous transplant or ≤ 1 cycle of chemotherapy in the 3 months previous to umbilical cord blood transplant (UCBT), and who should receive anti-thymocyte globulin as conditioning regimen. Conditioning Fludarabine dose of 40 mg/m2/day x 5, cyclophosphamide and total body irradiation with anti-thymocyte globulin followed by umbilical cord blood transplantation, and peri-transplant Mycophenolate Mofetil and Sirolimus.
Arm 3 - Refractory Leukemia/Lymphoma
ACTIVE COMPARATORArm 3 - patients with refractory leukemia or lymphoma who have been rendered aplastic either by induction chemotherapy or radioimmunoconjugated monoclonal antibody therapy. Conditioning Fludarabine dose of 40 mg/m2/day x 5, cyclophosphamide and total body irradiation with anti-thymocyte globulin followed by umbilical cord blood transplantation, and peri-transplant Mycophenolate Mofetil and Sirolimus.
Arm 4: MT2006-01 coenrolling patients
ACTIVE COMPARATORArm 4 - hematologic malignancy patients enrolled in MT2006-01. Conditioning Fludarabine dose of 40 mg/m2/day x 5, cyclophosphamide and total body irradiation with or without anti-thymocyte globulin followed by umbilical cord blood transplantation, and peri-transplant Mycophenolate Mofetil and Sirolimus.
Arm 5 - Previous Autologous Transplant
ACTIVE COMPARATORArm 5 - hematologic malignancy patients who have received a previous autologous transplant or ≥ 2 cycle of multiagent chemotherapy within the last 3 months previous to umbilical cord blood transplant (UCBT). Conditioning Fludarabine dose of 30 mg/m2/day x 5, cyclophosphamide and total body irradiation without anti-thymocyte globulin followed by umbilical cord blood transplantation, and peri-transplant Mycophenolate Mofetil and Sirolimus.
Arm 6 - No prior autologous transplant
ACTIVE COMPARATORArm 6 - hematologic malignancy patients who have not been treated with prior autologous transplant or ≤ 1 cycle of chemotherapy in the 3 months previous to umbilical cord blood transplant (UCBT), and who should receive anti-thymocyte globulin as conditioning regimen. Conditioning Fludarabine dose of 30 mg/m2/day x 5, cyclophosphamide and total body irradiation with anti-thymocyte globulin followed by umbilical cord blood transplantation, and peri-transplant Mycophenolate Mofetil and Sirolimus.
Interventions
Equine ATG dose is 15 mg/kg intravenously (IV) every 12 hours for 6 doses on days -6, - 5, and -4.
Cyclophosphamide 50mg/kg x 1 to be administered IV over 2 hours with high volume fluid flush on day -6.
Fludarabine 40 mg/m2/day or 30 mg/m2/day intravenously (IV) as one hour infusion x 5 days, on day -6 to -2.
Mycophenolate mofetil (MMF) 3 gram/day for patients who are ≥ 40 kg divided in 2 or 3 doses. Pediatric patient (\<40 kilograms) will receive MMF at the dose of 15 mg/kg/dose every 8 hours.
One or 2 UCB units may be infused to achieve the required cell dose.
Administered Day -1, 200 cGy
Sirolimus will be administered starting at day -3 with 8mg-12mg mg oral loading dose followed by single dose 4 mg/day with a target serum concentration of 3 to 12 mg/mL. Levels are to be monitored 3 times/week in the first 2 weeks, weekly until day +60, and as clinically indicated until day +100 post-transplantation. In the absence of acute GVHD sirolimus may be tapered starting at day +100 and eliminated by day +180 post-transplantation.
Eligibility Criteria
You may qualify if:
- Age, Graft Cell Dose and Graft HLA Criteria
- Subjects must be \<70 years old. Subjects ages ≥ 70 and ≤ 75 may be eligible if they have a Co-Morbidity Scoring (HCT-CI) score ≤ 2.
- The UCB graft is matched at 4-6 HLA-A, B, DRB1 antigens with the recipient.
- Patients co-enrolled in MT-2006-01 Phase I Study of Infusion of Umbilical Cord Blood Derived CD25+CD4+ T-Regulatory (Treg) Cells after Non-Myeloablative Cord\\Blood Transplantation will receive grafts composed of 2 UCB units.
- Disease Criteria:
- Acute Leukemias:
- Acute myeloid leukemia: high risk complete remission 1 (CR1) (as evidenced by preceding myelodysplastic syndrome (MDS), high risk cytogenetics such as those associated with MDS or complex karyotype, \> 2 cycles to obtain CR or erythroblastic and megakaryocytic); second or greater CR.
- Acute lymphoblastic leukemia/lymphoma: high risk CR1 as evidenced by high risk cytogenetics (e.g. t(9;22), t(1;19),t(4;11), other myeloid/lymphoid or mixed lineage leukemia \[MLL\] rearrangements, hypodiploidy or Ikaros family zinc finger 1 \[IKZF1\]), \> 1 cycle to obtain CR or evidence of minimal residual disease (MRD). Patients in second or greater CR are also eligible.
- Burkitt's lymphoma in CR2 or subsequent CR
- Natural Killer cell malignancies
- Chronic myelogenous leukemia: all types except refractory blast crisis. Chronic phase patients must have failed or been intolerant to Gleevec
- Myelodysplastic syndrome:
- Large-cell lymphoma, Hodgkin lymphoma and multiple myeloma with chemotherapy sensitive disease that has failed or patients who are ineligible for an autologous transplant.
- Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma, follicular lymphoma, which have progressed within 12 months 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 should be considered for debulking chemotherapy before transplant. Patients with refractory disease are eligible, unless has bulky disease and an estimated tumor doubling time of less than one month.
- Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are eligible after initial therapy if chemotherapy sensitive.
- +4 more criteria
You may not qualify if:
- \< 70 years with an available 5-6/6 HLA-A, B, DRB1 matched sibling donor
- Pregnancy or breastfeeding
- Evidence of human immunodeficiency virus (HIV) infection or known HIV positive serology
- Current active serious infection
- Unless in post-chemotherapy and radioimmunoconjugated antibody induced aplasia, when he/she would be eligible for Arm 3, patients with acute leukemia in morphologic relapse/ persistent disease defined as \> 5% blasts in normocellular bone marrow OR any % blasts if blasts have unique morphologic markers (e.g. Auer rods) or associated cytogenetic markers that allows morphologic relapse to be distinguished are not eligible.
- Chronic myelogenous leukemia (CML) in refractory blast crisis
- Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressive on salvage therapy. Stable disease is acceptable to move forward provided it is non-bulky.
- Active central nervous system malignancy
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, 55455, United States
Related Publications (5)
Bachanova V, Verneris MR, DeFor T, Brunstein CG, Weisdorf DJ. Prolonged survival in adults with acute lymphoblastic leukemia after reduced-intensity conditioning with cord blood or sibling donor transplantation. Blood. 2009 Mar 26;113(13):2902-5. doi: 10.1182/blood-2008-10-184093. Epub 2009 Jan 28.
PMID: 19179301BACKGROUNDBrunstein CG, Cantero S, Cao Q, Majhail N, McClune B, Burns LJ, Tomblyn M, Miller JS, Blazar BR, McGlave PB, Weisdorf DJ, Wagner JE. Promising progression-free survival for patients low and intermediate grade lymphoid malignancies after nonmyeloablative umbilical cord blood transplantation. Biol Blood Marrow Transplant. 2009 Feb;15(2):214-22. doi: 10.1016/j.bbmt.2008.11.013.
PMID: 19167681RESULTBachanova V, Burke MJ, Yohe S, Cao Q, Sandhu K, Singleton TP, Brunstein CG, Wagner JE, Verneris MR, Weisdorf DJ. Unrelated cord blood transplantation in adult and pediatric acute lymphoblastic leukemia: effect of minimal residual disease on relapse and survival. Biol Blood Marrow Transplant. 2012 Jun;18(6):963-8. doi: 10.1016/j.bbmt.2012.02.012. Epub 2012 Mar 16.
PMID: 22430088DERIVEDBachanova V, Sandhu K, Yohe S, Cao Q, Burke MJ, Verneris MR, Weisdorf D. Allogeneic hematopoietic stem cell transplantation overcomes the adverse prognostic impact of CD20 expression in acute lymphoblastic leukemia. Blood. 2011 May 12;117(19):5261-3. doi: 10.1182/blood-2011-01-329573. Epub 2011 Mar 14.
PMID: 21403127DERIVEDMacMillan 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
Related Links
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
- PRINCIPAL INVESTIGATOR
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
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 21, 2006
First Posted
March 22, 2006
Study Start
June 1, 2005
Primary Completion
December 12, 2019
Study Completion
December 12, 2019
Last Updated
November 19, 2020
Results First Posted
November 2, 2020
Record last verified: 2020-10