Single vs Double Umbilical Cord Blood Transplants in Children With High Risk Leukemia and Myelodysplasia (BMT CTN 0501)
13. oktober 2021 opdateret af: Medical College of Wisconsin
Multi-center, Open Label, Randomized Trial Comparing Single Versus Double Umbilical Cord Blood (UCB) Transplantation in Pediatric Patients With High Risk Leukemia and Myelodysplasia (BMT CTN #0501)
This study is a Phase III, randomized, open-label, multi-center, prospective study of single umbilical cord blood (UCB) transplantation versus double UCB transplantation in pediatric patients with hematologic malignancies.
Studieoversigt
Status
Afsluttet
Betingelser
Detaljeret beskrivelse
BACKGROUND:
In nearly every large single center or registry analysis of outcomes after UCB transplantation, cell dose is identified as an important factor influencing the incidence and rate of hematopoietic recovery, risk of transplant-related mortality, and probability of survival. Pilot data suggest that infusion of two partially human leukocyte antigen (HLA)-matched UCB units, which always augments the graft cell dose, is safe and may improve neutrophil recovery and survival. To determine whether the infusion of two UCB units enhances survival, a multi-center, open-label, randomized trial is proposed. As adequate single UCB units can be identified for more than 80% of pediatric recipients (in contrast to less than 30% for adults), this study will be open only to pediatric patients. The population will be restricted to patients with high-risk hematologic malignancy, the most common indication of UCB transplantation in children.
DESIGN NARRATIVE:
Participants will include patients 1 to 21 years of age with a diagnosis of hematological malignancy and with two partially HLA-matched UCB units. Units must be HLA-matched at 3 of 6 HLA-A and B (intermediate resolution molecular typing) and DRB1 (high resolution molecular typing) with each other and 4 of 6 with the recipient. Two appropriately HLA-matched units must be available such that one unit delivers a pre-cryopreserved, nucleated cell dose of at least 2.5 x 10^7 per kilogram and the second unit delivers at least 1.5 x 10^7 per kilogram.
Patients will be randomized no more than 14 days prior to initiation of conditioning. UCB units will be shipped prior to initiation of conditioning.
The preparative regimen will consist of the following:
- Fludarabine: 25 mg/m2/day IV on Days -10, -9, and -8.
- Total Body Irradiation (TBI): 165 cGy twice daily on Days -7, -6, -5, and -4.
- Cyclophosphamide: 60 mg/kg/day x 2 on Days -3 and -2.
- Day 0 will be the day of the UCB transplant. The Graft-vs-Host-Disease (GVHD) prophylaxis regimen will be mycophenolate mofetil (MMF) 15 mg/kg IV BID on Day -3 to Day + 45 and cyclosporine A (CSA) to maintain level 200-400 ng/mL beginning on Day -3.
Patients will be followed for at least 24 months post-transplant.
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
224
Fase
- Fase 3
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
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New South Wales
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Westmead, New South Wales, Australien, 2145
- Children's Hospital at Westmead
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British Columbia
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Vancouver, British Columbia, Canada, V5Z 4E3
- BC Cancer Agency
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Alabama
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Birmingham, Alabama, Forenede Stater, 35294
- University Of Alabama
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Arizona
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Phoenix, Arizona, Forenede Stater, 85016
- Phoenix Children's Hospital
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California
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Duarte, California, Forenede Stater, 91010
- City of Hope National Medical Center
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Oakland, California, Forenede Stater, 94609
- Childrens Hospital at Oakland
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San Diego, California, Forenede Stater, 92123
- UCSD/Rady Childrens Hospital
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San Francisco, California, Forenede Stater, 94143
- University of California, San Francisco (Peds)
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Colorado
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Denver, Colorado, Forenede Stater, 80218
- The Children's Hospital of Denver
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District of Columbia
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Washington, District of Columbia, Forenede Stater, 20010
- Children's National Medical Center
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Florida
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Gainesville, Florida, Forenede Stater, 32610
- University of Florida College of Medicine (Shands)
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Jacksonville, Florida, Forenede Stater, 32207
- Nemours Childrens Clinic
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Miami, Florida, Forenede Stater, 33136
- University of Miami
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Saint Petersburg, Florida, Forenede Stater, 33710
- All Children's Hospital
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Georgia
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Atlanta, Georgia, Forenede Stater, 30322-1062
- Children's Healthcare of Atlanta
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Indiana
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Indianapolis, Indiana, Forenede Stater, 46202
- Indiana University Medical Center
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Kentucky
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Louisville, Kentucky, Forenede Stater, 40202
- University of Louisville/Kosiar Children's Hospital
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Louisiana
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New Orleans, Louisiana, Forenede Stater, 70118
- Children's of New Orleans
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Massachusetts
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Boston, Massachusetts, Forenede Stater, 02115
- DFCI/Children's Hospital of Boston
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Michigan
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Ann Arbor, Michigan, Forenede Stater, 48109
- University of Michigan Medical Center
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Detroit, Michigan, Forenede Stater, 48201
- Karmanos Cancer Institute/Children's Hospital of Michigan
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Minnesota
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Minneapolis, Minnesota, Forenede Stater, 55455
- University of Minnesota
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Mississippi
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Jackson, Mississippi, Forenede Stater, 39216
- University of Mississippi
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Missouri
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Kansas City, Missouri, Forenede Stater, 64108
- Children's Mercy Hospital and Clinics
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New York
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Valhalla, New York, Forenede Stater, 10595
- New York Medical College
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North Carolina
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Durham, North Carolina, Forenede Stater, 27705
- Duke University Medical Center
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Ohio
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Columbus, Ohio, Forenede Stater, 43205-2696
- Nationwide Children's Hospital
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Oregon
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Portland, Oregon, Forenede Stater, 97239
- Oregon Health Sciences University
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Pennsylvania
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Philadelphia, Pennsylvania, Forenede Stater, 19104
- Children's Hospital of Philadelphia
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South Carolina
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Charleston, South Carolina, Forenede Stater, 29425
- Medical University of South Carolina
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Tennessee
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Nashville, Tennessee, Forenede Stater, 37232-7610
- Vanderbilt University Medical Center
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Texas
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Dallas, Texas, Forenede Stater, 75235
- Children's Medical Center of Dallas
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Fort Worth, Texas, Forenede Stater, 76104
- Cook Childrens Medical Center
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San Antonio, Texas, Forenede Stater, 78229
- Texas Transplant Institute
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Utah
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Salt Lake City, Utah, Forenede Stater, 84132
- Utah BMT/University of Utah Medical School
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Virginia
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Richmond, Virginia, Forenede Stater, 23298
- Virgina Commonwealth University
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Washington
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Seattle, Washington, Forenede Stater, 98109
- Fred Hutchinson Cancer Research Center
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Wisconsin
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Milwaukee, Wisconsin, Forenede Stater, 53211
- Medical College of Wisconsin
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Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
1 år til 21 år (Barn, Voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
Inclusion Criteria:
- Two partially HLA-matched UCB units. Units must be HLA-matched minimally at 4 of 6 HLA-A and B (at intermediate resolution by molecular typing) and DRB1 (at high resolution by molecular typing) loci with the patient, and the units must be HLA-matched at 3 of 6 HLA- A, B, DRB1 loci with each other (using same resolution of molecular typing as indicated above). Two appropriately HLA-matched units must be available such that one unit delivers a pre-cryopreserved nucleated cell dose of at least 2.5 x 10^7 per kilogram and the second unit at least 1.5 x 10^7 per kilogram.
Acute myelogenous leukemia (AML) at the following stages:
High risk first complete remission (CR1), defined as the following:
- Having preceding myelodysplasia (MDS)
- High risk cytogenetics (high risk cytogenetics: del (5q) -5, -7, abn (3q), t (6;9) complex karyotype [at least 5 abnormalities],)the presence of a high FLT3 ITD-AR (> 0.4)
- Requiring more than 1 cycle of chemotherapy to obtain complete remission (CR);
- FAB M6
- Second or greater CR
- First relapse with less than 25% blasts in bone marrow
- Morphologic complete remission with incomplete blood count recovery
- Therapy-related AML for which prior malignancy has been in remission for at least 12 months
Acute lymphocytic leukemia (ALL) at the following stages:
High risk first remission, defined as one of the following conditions:
- Philadelphia chromosome-positive adult lymphoblastic leukemia (Ph+ ALL)
- Mixed lineage leukemia (MLL) rearrangement with slow early response (defined as having M2 [5-25% blasts] or M3 [more than 25% blasts on bone marrow examination on Day 14 of induction therapy])
- Hypodiploidy (less than 44 chromosomes or DNA index less than 0.81)
- End of induction M3 bone marrow
- End of induction M2 with M2-3 at Day 42
- Evidence of minimal residual disease (MRD). If a patient's only high risk criterion is MRD, approval by a protocol chair or protocol officer is required for enrollment. For COG centers, this will only be for MRD greater than 1 percent by flow MRD at the end of extended induction.
High risk second remission, defined as one of the following conditions:
- Philadelphia chromosome-positive adult lymphoblastic leukemia (Ph+ ALL)
- Bone marrow relapse less than 36 months from induction
- T-lineage relapse at any time
- Very early isolated central nervous system (CNS) relapse (6 months from diagnosis)
- Slow reinduction (M2-3 at Day 28) after relapse at any time
- Evidence of minimal residual disease (MRD). If a patient's only high risk criterion is MRD, approval by a protocol chair or protocol officer is required for enrollment. For COG centers, this will only be for MRD greater than 1 percent by flow MRD at the end of extended induction.
- Any third or subsequent CR
- NK cell lymphoblastic leukemia in any CR
- Biphenotypic or undifferentiated leukemia in any CR or if in first relapse must have less than 25% blasts in bone marrow (BM)
- Myelodysplastic syndrome (MDS) at any stage
- Chronic myelogenous leukemia (CML) in chronic or accelerated phase
- All patients with evidence of CNS leukemia must be treated and be in CNS CR to be eligible for study.
- Patients 16 years old or older must have a Karnofsky score of at least 70% and patients younger than 16 years old must have a Lansky score of at least 70%.
Patients with adequate physical function as measured by:
- Cardiac: Left ventricular ejection fraction greater than 40% or shortening fraction greater than 26%
- Hepatic: Bilirubin no more than 2.5 mg/dL; alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) no more than 5 times the upper limit of normal (ULN)
- Renal: Serum creatinine within normal range for age, or if serum creatinine is outside normal range for age, then renal function (creatinine clearance or GFR) greater than 70 mL/min/1.73 m^2
- Pulmonary: Diffusing capacity of the lung for carbon monoxide (DLCO), forced expiratory volume in one second (FEV1), or forced vital capacity (FVC) greater than 50% of predicted value (corrected for hemoglobin); if unable to perform pulmonary function tests, then O2 saturation greater than 92% of room air
Exclusion Criteria:
- Pregnant (β-positive human chorionic gonadotropin [HCG]) or breastfeeding
- Evidence of HIV infection or HIV positive serology
- Current uncontrolled bacterial, viral, or fungal infection (currently taking medication and progression of clinical symptoms)
- Autologous transplant less than 12 months prior to enrollment
- Prior autologous transplant for the disease for which the UCB transplant will be performed
- Prior allogeneic hematopoietic stem cell transplant
- Active malignancy other than the one for which the UCB transplant is being performed within 12 months of enrollment
- Inability to receive TBI
- Requirement of supplemental oxygen
- HLA-matched related donor able to donate
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Eksperimentel: Single Cord Blood Transplant
Unrelated donor, single umbilical cord blood unit transplant; conditioning regimen: Total Body Irradiation/cyclophosphamide/fludarabine; GVHD prophylaxis: Cyclosporine A/Mycophenolate Mofetil
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Unrelated donor, single umbilical cord blood unit; conditioning regimen: TBI/cyclophosphamide/fludarabine; GVHD prophylaxis: cyclosporine/MMF
The TBI will be delivered from either a linear accelerator or cobalt source at a dose rate of between 4 and 26 cGy/minute using energies of between 1 and 25 MV.
Andre navne:
Cyclophosphamide 60 mg/kg/day will be administered as a 2 hour intravenous infusion with a high volume fluid flush on Days -3 and -2.
Andre navne:
Fludarabine 25 mg/m2/day will be administered over 30-60 minutes intravenous infusion on Days -10 through -8.
Fludarabine will not be dose adjusted for body weight.
Andre navne:
CSA will be administered beginning on Day -3 and doses will be adjusted to maintain a level of 200-400 ng/mL by TDX method (or 100-250 ng/mL by Tandem MS or equivalent level for other CSA testing methods).
CSA can be administered per institutional practice.
Andre navne:
MMF will be given at a dose of 1 gram IV q 8 hours if > 50 kg or 15 mg/kg IV q 8 hours if < 50 kg beginning the morning of Day -3.
Andre navne:
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Eksperimentel: Double Cord Blood Transplant
Unrelated donor, double umbilical cord blood unit transplant; Conditioning regimen: Total Body Irradiation/cyclophosphamide/fludarabine; GVHD prophylaxis: Cyclosporine A/Mycophenolate Mofetil
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The TBI will be delivered from either a linear accelerator or cobalt source at a dose rate of between 4 and 26 cGy/minute using energies of between 1 and 25 MV.
Andre navne:
Cyclophosphamide 60 mg/kg/day will be administered as a 2 hour intravenous infusion with a high volume fluid flush on Days -3 and -2.
Andre navne:
Fludarabine 25 mg/m2/day will be administered over 30-60 minutes intravenous infusion on Days -10 through -8.
Fludarabine will not be dose adjusted for body weight.
Andre navne:
CSA will be administered beginning on Day -3 and doses will be adjusted to maintain a level of 200-400 ng/mL by TDX method (or 100-250 ng/mL by Tandem MS or equivalent level for other CSA testing methods).
CSA can be administered per institutional practice.
Andre navne:
MMF will be given at a dose of 1 gram IV q 8 hours if > 50 kg or 15 mg/kg IV q 8 hours if < 50 kg beginning the morning of Day -3.
Andre navne:
Unrelated donor, double umbilical cord blood unit; Conditioning regimen: TBI/cyclophosphamide/fludarabine; GVHD prophylaxis: cyclosporine/MMF
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Percentage of Participants With Overall Survival
Tidsramme: 1 year post-randomization
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Overall survival is defined as survival of death from any cause.
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1 year post-randomization
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Percentage of Participants With Disease-free Survival
Tidsramme: 1 year post-randomization
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Disease-free survival is defined as survival without relapse of the primary disease.
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1 year post-randomization
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Percentage of Participants With Neutrophil and Platelet Engraftment
Tidsramme: Days 42 and 100
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Neutrophil engraftment is defined as achieving an absolute neutrophil count greater than 500x10^6/liter for three consecutive measurements on different days.
The first of the three days will be designated the day of neutrophil engraftment.
Platelet engraftment is defined as achieving platelet counts greater than 50,000/microliter for consecutive measurements over 7 days without requiring platelet transfusions.
The first of the 7 days will be designated the day of platelet engraftment.
Subjects must not have had platelet transfusions during the preceding 7 days.
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Days 42 and 100
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Time to Neutrophil and Platelet Engraftment
Tidsramme: 2 years post-transplant
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Platelet engraftment is defined as achieving platelet counts greater than 50,000/microliter for consecutive measurements over 7 days without requiring platelet transfusions.
The first of the 7 days will be designated the day of platelet engraftment.
Subjects must not have had platelet transfusions during the preceding 7 days.
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2 years post-transplant
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Percentage of Participants With Acute Graft-versus-host Disease (GVHD)
Tidsramme: Day 100 post-randomization
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Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995: Skin stage: 0: No rash
Liver stage (based on bilirubin level)*: 0: <2 mg/dL
GI stage*: 0: No diarrhea or diarrhea <500 mL/day
GVHD grade: 0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4 |
Day 100 post-randomization
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Percentage of Participants With Chronic GVHD
Tidsramme: 1 year post-randomization
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Incidences of chronic GVHD will be graded per Shulman et al. 1980.
This reference categorizes chronic GVHD as either limited or extensive.
For this outcome, participants developing either type are considered to have a chronic GVHD event.
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1 year post-randomization
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Number of Infections Per Participant
Tidsramme: 2 years post-randomization
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2 years post-randomization
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Percentage of Participants With Relapse
Tidsramme: 1 year post-randomization
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Relapse is defined by either morphological or cytogenetic evidence of AML, ALL, CML, or MDS consistent with pre-transplant features.
Testing for recurrent malignancy in the blood, marrow or other sites will be used to assess relapse after transplantation.
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1 year post-randomization
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Percentage of Participants With Treatment-related Mortality
Tidsramme: 1 year post-randomization
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Treatment related mortality is defined as death without relapse of the primary disease.
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1 year post-randomization
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Number of Participants With Engraftment Syndrome
Tidsramme: Day 100 post-transplant
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Day 100 post-transplant
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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Generelle publikationer
- Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE, Hackman R, Tsoi MS, Storb R, Thomas ED. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med. 1980 Aug;69(2):204-17. doi: 10.1016/0002-9343(80)90380-0.
- Wagner JE Jr, Eapen M, Carter S, Wang Y, Schultz KR, Wall DA, Bunin N, Delaney C, Haut P, Margolis D, Peres E, Verneris MR, Walters M, Horowitz MM, Kurtzberg J; Blood and Marrow Transplant Clinical Trials Network. One-unit versus two-unit cord-blood transplantation for hematologic cancers. N Engl J Med. 2014 Oct 30;371(18):1685-94. doi: 10.1056/NEJMoa1405584.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. december 2006
Primær færdiggørelse (Faktiske)
1. marts 2014
Studieafslutning (Faktiske)
1. oktober 2014
Datoer for studieregistrering
Først indsendt
14. december 2006
Først indsendt, der opfyldte QC-kriterier
14. december 2006
Først opslået (Skøn)
18. december 2006
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
28. oktober 2021
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
13. oktober 2021
Sidst verificeret
1. oktober 2021
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Sygdomme i immunsystemet
- Neoplasmer efter histologisk type
- Neoplasmer
- Lymfoproliferative lidelser
- Lymfesygdomme
- Immunproliferative lidelser
- Knoglemarvssygdomme
- Hæmatologiske sygdomme
- Myeloproliferative lidelser
- Leukæmi, lymfoid
- Myelodysplastiske syndromer
- Leukæmi
- Leukæmi, myeloid
- Leukæmi, Myeloid, Akut
- Precursorcelle lymfoblastisk leukæmi-lymfom
- Leukæmi, myelogen, kronisk, BCR-ABL positiv
- Lægemidlers fysiologiske virkninger
- Molekylære mekanismer for farmakologisk virkning
- Anti-infektionsmidler
- Enzymhæmmere
- Antirheumatiske midler
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Antineoplastiske midler, Alkylering
- Alkyleringsmidler
- Myeloablative agonister
- Dermatologiske midler
- Antibakterielle midler
- Antibiotika, antineoplastisk
- Antifungale midler
- Antituberkulære midler
- Antibiotika, Antituberkulær
- Calcineurin-hæmmere
- Cyclofosfamid
- Fludarabin
- Mycophenolsyre
- Cyclosporin
- Cyclosporiner
Andre undersøgelses-id-numre
- BMTCTN0501
- 5U24CA076518 (U.S. NIH-bevilling/kontrakt)
- 2U01HL069294 (U.S. NIH-bevilling/kontrakt)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
JA
IPD-planbeskrivelse
Findings were published in a manuscript.
IPD-delingstidsramme
Within 6 months of official study closure at participating sites.
IPD-delingsadgangskriterier
Available to the public.
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .