NCT00498316

Brief Summary

The goal of this clinical research study is to learn if combining cord blood units will be safe and result in the cells "taking" faster in recipients. The cord blood units will have their cell number increased in the lab using cells from a family member or they will be collected from an unrelated healthy donor.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
98

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Jul 2007

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

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 3, 2007

Completed
3 days until next milestone

First Submitted

Initial submission to the registry

July 6, 2007

Completed
4 days until next milestone

First Posted

Study publicly available on registry

July 10, 2007

Completed
9.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2016

Completed
Last Updated

February 28, 2020

Status Verified

October 1, 2016

Enrollment Period

9.3 years

First QC Date

July 6, 2007

Last Update Submit

February 27, 2020

Conditions

Keywords

Myelodysplastic SyndromeLeukemiaCord Blood ExpansionUmbilical Cord BloodMesenchymal Stem CellsAcute Myelogenous LeukemiaAcute Lymphoblastic LeukemiaALLAMLMDS

Outcome Measures

Primary Outcomes (1)

  • Engraftment and Time to Engraftment

    Engraftment defined as a sustained ANC \> 0.5 x 109/L for 3 consecutive days and evidence of donor chimerism or autologous reconstitution by D+42

    100 days after transplant, then every 3 months thereafter

Study Arms (1)

Cord Blood Infusion

OTHER

Cord blood transplantation performed on day 0. Busulfan 32 mg/m2 by vein as an outpatient before Day -14 or as an inpatient on Day -9, and AUC of 4,000 microMol.min-1 by vein on Days -7 to -4. Fludarabine 10 mg/m2 by vein on Days -7 to -4, 40 mg/m2 by vein on Days -6 to -3 or on Days -5 to -2. Rituximab 375 mg/m2 by vein on Day -9. ATG 1.25 mg/Kg by vein on Day -4 and 1.75 mg/Kg by vein on Day -3, 1.25 mg/kg by vein on Day -3 and 1.75 mg/kg by vein on Day -2. Cyclophosphamide 50 mg/kg by vein on Day -6. Clofarabine 30 mg/m2 by vein on Days -7 to -4. Total body irradiation (TBI) 200 cGy at 25 cGy/minute delivered on Day -3. Melphalan 140 mg/m2 by vein on Day -2. Tacrolimus 0.03 mg/kg by vein daily starting on D-2, to be changed to oral dosing when tolerated. Tacrolimus is to be tapered around Day +180, if no GVHD is present.

Procedure: Cord Blood InfusionDrug: BusulfanDrug: FludarabineDrug: RituximabOther: ATGDrug: CyclophosphamideDrug: ClofarabineRadiation: Total Body Irradiation (TBI)Drug: MelphalanDrug: TacrolimusDrug: Mycophenolate MofetilDrug: G-CSF

Interventions

Cord blood transplantation performed on day 0.

Cord Blood Infusion

32 mg/m2 by vein as an outpatient before Day -14 or as an inpatient on Day -9, and AUC of 4,000 microMol.min-1 by vein on Days -7 to -4 for patients with ALL, AML, NHL, CLL, CML, HD, and MM who are \>1 and \< 55 years old. Patients \>55 but \< 65 years who have a Performance Status of 0 or 1 and no comorbidities may receive the myeloablative regimen 4 at the discretion of the investigator(s).

Also known as: Busulfex, Myleran
Cord Blood Infusion

10 mg/m2 by vein on Days -7 to -4 for patients with ALL, AML, NHL, CLL, CML, HD, and MM who are \>1 and \< 55 years old. Patients \>55 but \< 65 years who have a Performance Status of 0 or 1 and no comorbidities may receive the myeloablative regimen 4 at the discretion of the investigator(s). 40 mg/m2 by vein on Days -6 to -3 for patients with AML, ALL, NHL, CLL,CML, HD and MM who are \> 55 and \< 80 years old or of any age with co-morbid condition that in the opinion of the investigators would preclude myeloablative therapy. 40 mg/m2 by vein on Days -5 to -2 for patients with AML, ALL, NHL, CLL, CML, and HD who are \>1 and \< 80 years old that in the opinion of the investigator(s) would preclude myeloablative therapy and who cannot receive Total Body Irradiation (TBI) may receive the reduced intensity treatment regimen 3.

Also known as: Fludarabine Phosphate, Fludara
Cord Blood Infusion

375 mg/m2 by vein on Day -9 for patients with AML, ALL, NHL, CLL,CML, HD and MM who are \> 55 and \< 80 years old or of any age with co-morbid condition that in the opinion of the investigators would preclude myeloablative therapy.

Also known as: Rituxan
Cord Blood Infusion
ATGOTHER

1.25 mg/Kg by vein on Day -4 and 1.75 mg/Kg by vein on Day -3 for patients with AML, ALL, NHL, CLL,CML, HD and MM who are \> 55 and \< 80 years old or of any age with co-morbid condition that in the opinion of the investigators would preclude myeloablative therapy. 1.25 mg/kg by vein on Day -3 and 1.75 mg/kg by vein on Day -2 for patients with AML, ALL, NHL, CLL, CML, and HD who are \>1 and \< 80 years old that in the opinion of the investigator(s) would preclude myeloablative therapy and who cannot receive Total Body Irradiation (TBI) may receive the reduced intensity treatment regimen 3.

Also known as: Antithymocyte Globulin, Thymoglobulin
Cord Blood Infusion

50 mg/kg by vein on Day -6 for patients with AML, ALL, NHL, CLL,CML, HD and MM who are \> 55 and \< 80 years old or of any age with co-morbid condition that in the opinion of the investigators would preclude myeloablative therapy.

Also known as: Cytoxan, Neosar
Cord Blood Infusion

30 mg/m2 by vein on Days -7 to -4 for patients with ALL, AML, NHL, CLL, CML, HD, and MM who are \>1 and \< 55 years old. Patients \>55 but \< 65 years who have a Performance Status of 0 or 1 and no comorbidities may receive the myeloablative regimen 4 at the discretion of the investigator(s).

Also known as: Clofarex, Clolar
Cord Blood Infusion

200 cGy at 25 cGy/minute delivered on Day -3.

Also known as: TBI, XRT
Cord Blood Infusion

140 mg/m2 by vein on Day -2 for patients with AML, ALL, NHL, CLL, CML, and HD who are \>1 and \< 80 years old that in the opinion of the investigator(s) would preclude myeloablative therapy and who cannot receive Total Body Irradiation (TBI) may receive the reduced intensity treatment regimen 3.

Also known as: Alkeran
Cord Blood Infusion

0.03 mg/kg by vein daily starting on D-2, to be changed to oral dosing when tolerated. Tacrolimus is to be tapered around Day +180, if no GVHD is present.

Also known as: Prograf
Cord Blood Infusion

1 gram by vein twice a day Days -3 through Day 100.

Also known as: MMF, CellCept
Cord Blood Infusion
G-CSFDRUG

5 mcg/kg/day subcutaneously beginning on day 0, and continuing until the absolute neutrophil count (ANC) is \> 2.5 x 109/L.

Also known as: Filgrastim, Neupogen
Cord Blood Infusion

Eligibility Criteria

Age1 Year - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Patients must have one of the following hematologic malignancies: Acute Myelogenous Leukemia (AML), induction failure, high-risk for relapse first remission (with intermediate-risk or high-risk cytogenetics, flt3 mutation positive and/or evidence of minimal residual disease by flow cytometry), secondary leukemia from prior chemotherapy and/or arising from MDS, Langerhan's cell histiocytosis, any disease beyond first remission; or,
  • Myelodysplastic Syndrome (MDS): Primary or therapy related; or,
  • Acute Lymphoblastic Leukemia (ALL): induction failure, primary refractory to treatment (do not achieve complete remission after first course of therapy) or are beyond first remission including second or greater remission or active disease.
  • #3, continued: Patients in first remission are eligible if they are considered high risk, defined as any of the following detected at any time: with translocations 9;22 or 4;11, hypodiploidy, complex karyotype, secondary leukemia developing after cytotoxic drug exposure, and/or evidence of minimal residual disease, or acute biphenotypic leukemia, or double hit non-Hodgkin's lymphoma; or,
  • Non-Hodgkin's Lymphoma (NHL) in second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant). Double hit lymphomas in first remission or more advanced disease; or,
  • Small Lymphocytic Lymphoma (SLL), or Chronic Lymphocytic Leukemia (CLL) with progressive disease following standard therapy; or,
  • CML second chronic phase or accelerated phase; or,
  • Hodgkin's Disease (HD): Induction failures, second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant); or,
  • Multiple Myeloma: stage II or III, symptomatic, secretory Multiple Myeloma requiring treatment.
  • Age greater than or equal to 1 year but less than or equal to 55 years (Myeloablative Regimen 4). Eligibility for pediatric patients will be determined in conjunction with an MD Anderson Cancer Center (MDACC) pediatrician. Patients \>55 but \< 65 years who have a Performance Status of 0 or 1 and no comorbidities may receive the myeloablative regimen 4 at the discretion of the investigator(s).
  • Age greater than 55 years and less than or equal to 80 years (Nonmyeloablative Regimen 2)
  • Age greater than or equal to 1 but less than or equal to 80 years old that in the opinion of the investigator(s) would preclude myeloablative therapy and who cannot receive Total Body Irradiation (TBI) may receive reduced intensity regimen 3.
  • Performance score of at least 60% by Karnofsky or PS less than 3 (ECOG) (age greater than or equal to 12 years), or Lansky Play-Performance Scale of at least 60% or greater (age \<12 years)
  • Left ventricular ejection fraction of at least 40% (Myeloablative Regimen 4, Reduced Intensity Regimen 3) or 30% (Nonmyeloablative Regimen 2)
  • Pulmonary function test demonstrating a diffusion capacity of least 50% predicted (Myeloablative Regimen 4, Reduced Intensity Regimen 3) or at least 40% predicted (Nonmyeloablative Regimen 2). For children \< 7 years of age who are unable to perform pulmonary function test (PFT), oxygen saturation \> 92% on room air by pulse oximetry.
  • +7 more criteria

You may not qualify if:

  • HIV positive
  • Positive beta HCG in female of child-bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization or breast-feeding.
  • Uncontrolled serious medical condition such as persistent septicemia despite adequate antibiotic therapy, decompensated congestive heart failure despite cardiac medications or pulmonary insufficiency requiring intubation. (excluding primary disease for which CB transplantation is proposed), or psychiatric condition that would limit informed consent.
  • Active central nervous system (CNS) disease in patient with history of CNS malignancy.
  • Availability of appropriate, willing, HLA-matched related marrow donor.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

  • de Lima M, McNiece I, Robinson SN, Munsell M, Eapen M, Horowitz M, Alousi A, Saliba R, McMannis JD, Kaur I, Kebriaei P, Parmar S, Popat U, Hosing C, Champlin R, Bollard C, Molldrem JJ, Jones RB, Nieto Y, Andersson BS, Shah N, Oran B, Cooper LJ, Worth L, Qazilbash MH, Korbling M, Rondon G, Ciurea S, Bosque D, Maewal I, Simmons PJ, Shpall EJ. Cord-blood engraftment with ex vivo mesenchymal-cell coculture. N Engl J Med. 2012 Dec 13;367(24):2305-15. doi: 10.1056/NEJMoa1207285.

Related Links

MeSH Terms

Conditions

Myelodysplastic SyndromesLeukemiaLeukemia, Myeloid, AcutePrecursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Busulfanfludarabinefludarabine phosphateRituximabAntilymphocyte SerumthymoglobulinCyclophosphamideClofarabineWhole-Body IrradiationMelphalanTacrolimusMycophenolic AcidGranulocyte Colony-Stimulating FactorFilgrastim

Condition Hierarchy (Ancestors)

Bone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesNeoplasms by Histologic TypeNeoplasmsLeukemia, MyeloidLeukemia, LymphoidLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Butylene GlycolsGlycolsAlcoholsOrganic ChemicalsMesylatesAlkanesulfonatesAlkanesulfonic AcidsAlkanesHydrocarbons, AcyclicHydrocarbonsSulfonic AcidsSulfur AcidsSulfur CompoundsAntibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsImmune SeraBiological ProductsComplex MixturesPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedPhosphoramidesOrganophosphorus CompoundsAdenine NucleotidesPurine NucleotidesPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsArabinonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesNucleotidesRibonucleotidesRadiotherapyTherapeuticsInvestigative TechniquesPhenylalanineAmino Acids, AromaticAmino Acids, CyclicAmino AcidsMacrolidesLactonesCaproatesAcids, AcyclicCarboxylic AcidsFatty AcidsLipidsColony-Stimulating FactorsGlycoproteinsGlycoconjugatesCarbohydratesHematopoietic Cell Growth FactorsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesBiological Factors

Study Officials

  • Elizabeth Shpall, MD

    M.D. Anderson Cancer Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 6, 2007

First Posted

July 10, 2007

Study Start

July 3, 2007

Primary Completion

October 1, 2016

Study Completion

October 1, 2016

Last Updated

February 28, 2020

Record last verified: 2016-10

Locations