NCT02722668

Brief Summary

This is a phase II trial using a non-myeloablative cyclophosphamide/ fludarabine/total body irradiation (TBI) preparative regimen with modifications based on factors including diagnosis, disease status, and prior treatment. Single or double unit selected according to current University of Minnesota umbilical cord blood graft selection algorithm.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
15

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started May 2017

Longer than P75 for phase_2

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

First Submitted

Initial submission to the registry

March 24, 2016

Completed
6 days until next milestone

First Posted

Study publicly available on registry

March 30, 2016

Completed
1.1 years until next milestone

Study Start

First participant enrolled

May 15, 2017

Completed
5.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 22, 2023

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

February 22, 2024

Completed
1.4 years until next milestone

Results Posted

Study results publicly available

July 4, 2025

Completed
Last Updated

July 4, 2025

Status Verified

June 1, 2025

Enrollment Period

5.8 years

First QC Date

March 24, 2016

Results QC Date

April 18, 2025

Last Update Submit

June 18, 2025

Conditions

Keywords

AMLALLCMLCLLSLL

Outcome Measures

Primary Outcomes (1)

  • Probability of Acute Graft Versus Host Disease (GVHD)

    Simple proportions will be used to estimate the probability of grade II-IV actue GVHD.

    Day 100

Secondary Outcomes (7)

  • Incidence of Acute GVHD

    Day 100

  • Transplant Related Mortality

    6 months post transplant

  • Chimerism

    Day 21

  • Chimerism

    Day 100

  • Chimerism

    Day 180

  • +2 more secondary outcomes

Study Arms (2)

No Anti-thymocyte Globulin (ATG)

EXPERIMENTAL

Hematologic malignancy patients who have received a previous autologous transplant or ≥ 2 cycles of multi-agent chemotherapy within the 3 months previous to umbilical cord blood transplantation.

Drug: FludarabineDrug: CyclophosphamideDrug: MMFDrug: SirolimusRadiation: TBIBiological: Umbilical cord blood cell infusion

Anti-thymocyte Globulin (ATG)

EXPERIMENTAL

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 transplantation, should receive Anti-thymocyte Globulin (ATG) as part of their conditioning regimen.

Drug: FludarabineDrug: CyclophosphamideDrug: MMFDrug: SirolimusRadiation: TBIBiological: Umbilical cord blood cell infusionBiological: ATG

Interventions

Both Arms: 30 mg/m\^2 IV over 1 hour Day -6 to Day -2

Also known as: Fludara
Anti-thymocyte Globulin (ATG)No Anti-thymocyte Globulin (ATG)

Arm 1: 50 mg/kg IV over 2 hours Day -6

Also known as: Cytoxan
Anti-thymocyte Globulin (ATG)No Anti-thymocyte Globulin (ATG)
MMFDRUG

Both Arms: Mycophenolate mofetil (MMF) 3 gram/day IV/PO for patients who are ≥ 40 kg divided in 2 or 3 doses. In obese patients (\>125% IBW) 15 mg/kg every 12 hours may be considered. Pediatric patient (\<40 kilograms) will receive MMF at the dose of 15 mg/kg/dose every 8 hours beginning Day -3. MMF dosing will be monitored and altered as clinically appropriate based on institutional guidelines. Patients will be eligible for MMF dosing and pharmacokinetics studies. Stop MMF at Day +30 or 7 days after engraftment, whichever day is later, if no acute graft versus host disease (GVHD). (Definition of engraftment is 1st day of 3 consecutive days of absolute neutrophil count \[ANC) ≥ 0.5 x 109 /L\]). If no donor engraftment, do not stop MMF.

Also known as: Mycophenolate Mofetil
Anti-thymocyte Globulin (ATG)No Anti-thymocyte Globulin (ATG)

Both Arms: Adult Dosing: Sirolimus will be administered starting at Day -3 with 8-12 mg oral loading dose followed by single dose 4 mg/day with a target serum concentration of 3 to 12 mg/mL by high-performance liquid chromatography (HPLC) and will be monitored per institutional guidelines. In the absence of acute GVHD sirolimus may be tapered starting at Day +100 and eliminated by Day +180 post-transplantation. Pediatric Dosing: Sirolimus will be administered starting on Day -3 with an oral loading dose of 10 mg followed by maintenance dosing of 2.5 mg/m\^2/day (Maximum total daily dose of 4mg) as per institutional guidelines. Target serum concentration goals are 3 to 12 mg/mL by high-performance liquid chromatography (HPLC) and will be monitored per institutional guidelines.

Also known as: Rapamycin
Anti-thymocyte Globulin (ATG)No Anti-thymocyte Globulin (ATG)
TBIRADIATION

Both Arms: 200 cGy on Day -1

Also known as: Total body irradiation
Anti-thymocyte Globulin (ATG)No Anti-thymocyte Globulin (ATG)

Both Arms: Day 0

Also known as: UCB
Anti-thymocyte Globulin (ATG)No Anti-thymocyte Globulin (ATG)
ATGBIOLOGICAL

Arm 2: 15 mg/kg IV every 12 hours Day -6 to Day -4

Also known as: Anti-thymocyte Globulin
Anti-thymocyte Globulin (ATG)

Eligibility Criteria

AgeUp to 75 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Age, Performance Status, and Graft Criteria
  • \<70 years of age with no matched 5/6 or 6/6 sibling donor - patients ≥ 70 and ≤ 75 years of age may be eligible if they have a Co-Morbidity score ≤ 2 (http://www.qxmd.com/calculate-online/hematology/hct-ci)
  • Karnofsky score ≥ 70% (≥ 16 years) or Lansky score ≥ 50 (\< 16 years)
  • UCB graft selected according to current University of Minnesota umbilical cord blood graft selection algorithm
  • Eligible Diseases All diseases listed below are advanced hematologic malignancies not curable by conventional chemotherapy. Responses to conventional treatment range from zero to 30% but are typically short lived.
  • Acute Leukemias: Must be in remission by morphology (\<5% blasts). Note cytogenetic relapse or persistent disease without morphologic relapse is acceptable. Also a small percentage of blasts that is equivocal between marrow regeneration vs. early relapse are acceptable provided there are no associated cytogenetic markers consistent with relapse.
  • Acute Myeloid Leukemia (AML) and related precursor neoplasms: 2nd or greater complete remission (CR); first complete remission (CR1) in patients \> 60 years old; CR1 in ≤ 60 years old that is NOT considered as favorable-risk. Favorable risk AML is defined as having one of the following:
  • t(8,21) without cKIT mutation
  • inv(16) or t(16;16) without cKIT mutation
  • Normal karyotype with mutated NPM1 and wild type FLT-ITD
  • Normal karyotype with double mutated CEBPA
  • Acute prolymphocytic leukemia (APL) in first molecular remission at the end of consolidation
  • Acute lymphoblastic leukemia (ALL)/lymphoma: second or greater CR; CR1 unable to tolerate consolidation chemotherapy due to chemotherapy-related toxicities; CR1 high-risk ALL. High risk ALL is defined as having one of the following:
  • Evidence of high risk cytogenetics, e.g. t(9;22), t(1;19), t(4;11), other MLL rearrangements, IKZF1
  • years of age or older at diagnosis
  • +31 more criteria

You may not qualify if:

  • Pregnant or breast feeding. The agents used in this study include Pregnancy Category D: known to cause harm to a fetus. Females of childbearing potential must have a negative pregnancy test prior to starting therapy.
  • Untreated active infection
  • Active HIV infection or known HIV positive serology
  • Less than 3 months since prior myeloablative transplant
  • CML in blast crisis
  • Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressing on salvage therapy.
  • 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

Location

MeSH Terms

Conditions

Leukemia, Myeloid, AcutePrecursor Cell Lymphoblastic Leukemia-LymphomaBurkitt LymphomaLeukemia, Myelogenous, Chronic, BCR-ABL PositiveMyelodysplastic SyndromesDendritic Cell Sarcoma, InterdigitatingHodgkin DiseaseMultiple MyelomaLeukemia, Lymphocytic, Chronic, B-CellLymphoma, B-Cell, Marginal ZoneLymphoma, FollicularLymphoma, Mantle-CellLeukemia, ProlymphocyticBone Marrow Failure DisordersMyeloproliferative DisordersPrimary MyelofibrosisLeukemiaLymphoma, T-CellLeukemia, Plasma Cell

Interventions

fludarabinefludarabine phosphateCyclophosphamideMycophenolic AcidSirolimusWhole-Body IrradiationAntilymphocyte Serum

Condition Hierarchy (Ancestors)

Leukemia, MyeloidNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLeukemia, LymphoidLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLymphoma, B-CellLymphoma, Non-HodgkinLymphomaBone Marrow DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsHistiocytic Disorders, MalignantHistiocytosisNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic DisordersLeukemia, B-Cell

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsCaproatesAcids, AcyclicCarboxylic AcidsFatty AcidsLipidsMacrolidesLactonesRadiotherapyTherapeuticsInvestigative TechniquesImmune SeraAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsBiological ProductsComplex Mixtures

Results Point of Contact

Title
Dr. Margaret MacMillan
Organization
University of Minnesota, Masonic Cancer Center

Study Officials

  • Margaret MacMillan, MD, MSC

    University of Minnesota

    PRINCIPAL INVESTIGATOR

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 24, 2016

First Posted

March 30, 2016

Study Start

May 15, 2017

Primary Completion

February 22, 2023

Study Completion

February 22, 2024

Last Updated

July 4, 2025

Results First Posted

July 4, 2025

Record last verified: 2025-06

Locations