NCT00686556

Brief Summary

RATIONALE: Giving chemotherapy and total marrow irradiation before a donor umbilical cord blood or hematopoietic stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's 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 after the transplant may stop this from happening. PURPOSE: This phase I trial is studying the side effects and best dose of total marrow irradiation when given together with combination chemotherapy and umbilical cord blood hematopoietic stem cell transplant in treating patients with acute leukemia, acute myeloid leukemia or multiple myeloma that did not respond to previous therapy.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
12

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Aug 2012

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

First Submitted

Initial submission to the registry

May 29, 2008

Completed
1 day until next milestone

First Posted

Study publicly available on registry

May 30, 2008

Completed
4.2 years until next milestone

Study Start

First participant enrolled

August 1, 2012

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2016

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2016

Completed
Last Updated

December 5, 2017

Status Verified

December 1, 2017

Enrollment Period

4.3 years

First QC Date

May 29, 2008

Last Update Submit

December 3, 2017

Conditions

Acute Lymphoblastic LeukemiaMyelodysplastic SyndromeMultiple Myeloma

Keywords

recurrent adult acute lymphoblastic leukemiarecurrent childhood acute lymphoblastic leukemiarecurrent adult acute myeloid leukemiarecurrent childhood acute myeloid leukemiaadult acute myeloid leukemia with 11q23 (MLL) abnormalitiesadult acute myeloid leukemia with inv(16)(p13;q22)adult acute myeloid leukemia with t(15;17)(q22;q12)adult acute myeloid leukemia with t(16;16)(p13;q22)adult acute myeloid leukemia with t(8;21)(q22;q22)ALLMDS

Outcome Measures

Primary Outcomes (1)

  • Maximum tolerated dose (MTD) of total marrow irradiation (TMI)

    Maximum tolerated dose (MTD) is the highest dose of a drug or treatment that does not cause unacceptable side effects. The MTD of TMI will be determined by using the modified Continual Reassessment Method (CRM). The goal of this CRM will be to identify 1 of the 5 dose levels which corresponds to the desired maximum toxicity rate of \<=15%.

    Day 42 and 6 months

Secondary Outcomes (10)

  • Incidence of neutrophil engraftment

    Day 42

  • Incidence of platelet engraftment

    6 Months and 1 Year After Transplantation

  • Incidence of complete donor chimerism

    Day 100

  • Incidence of transplantation-related mortality

    6 Months

  • Incidence of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) after transplantation

    Day 100

  • +5 more secondary outcomes

Study Arms (5)

Cohort -1

EXPERIMENTAL

Patient receives preparative therapy including Fludarabine, cyclophosphamide, and total marrow irradiation of 12 Gy on Days -4 through -1, and starts immunosuppressive therapy using cyclosporine, Mycophenolate Mofetil, followed by umbilical cord blood transplantation, or HLA-matched related donor bone marrow transplantation and granulocyte colony-stimulating factor administration.

Drug: cyclophosphamideDrug: cyclosporineDrug: FludarabineDrug: mycophenolate mofetilRadiation: total marrow irradiationProcedure: umbilical cord blood transplantationBiological: Granulocyte colony-stimulating factorBiological: HLA-matched related donor bone marrow

Cohort 1

EXPERIMENTAL

Patient receives preparative therapy including Fludarabine, cyclophosphamide, and total marrow irradiation of 15 Gy on Days -5 through -1, and starts immunosuppressive therapy using cyclosporine, Mycophenolate Mofetil, followed by umbilical cord blood transplantation, or HLA-matched related donor bone marrow transplantation and granulocyte colony-stimulating factor administration.

Drug: cyclophosphamideDrug: cyclosporineDrug: FludarabineDrug: mycophenolate mofetilRadiation: total marrow irradiationProcedure: umbilical cord blood transplantationBiological: Granulocyte colony-stimulating factorBiological: HLA-matched related donor bone marrow

Cohort 2

EXPERIMENTAL

Patient receives preparative therapy including Fludarabine, cyclophosphamide, and total marrow irradiation of 18 Gy on Days -6 through -1, and starts immunosuppressive therapy using cyclosporine, Mycophenolate Mofetil, followed by umbilical cord blood transplantation, or HLA-matched related donor bone marrow transplantation and granulocyte colony-stimulating factor administration.

Drug: cyclophosphamideDrug: cyclosporineDrug: FludarabineDrug: mycophenolate mofetilRadiation: total marrow irradiationProcedure: umbilical cord blood transplantationBiological: Granulocyte colony-stimulating factorBiological: HLA-matched related donor bone marrow

Cohort 3

EXPERIMENTAL

Patient receives preparative therapy including Fludarabine, cyclophosphamide, and total marrow irradiation of 21 Gy on Days -7 through -1, and starts immunosuppressive therapy using cyclosporine, Mycophenolate Mofetil, followed by umbilical cord blood transplantation, or HLA-matched related donor bone marrow transplantation and granulocyte colony-stimulating factor administration.

Drug: cyclophosphamideDrug: cyclosporineDrug: FludarabineDrug: mycophenolate mofetilRadiation: total marrow irradiationProcedure: umbilical cord blood transplantationBiological: Granulocyte colony-stimulating factorBiological: HLA-matched related donor bone marrow

Cohort 4

EXPERIMENTAL

Patient receives preparative therapy including Fludarabine, cyclophosphamide, and total marrow irradiation of 24 Gy on Days -8 through -1, and starts immunosuppressive therapy using cyclosporine, Mycophenolate Mofetil, followed by umbilical cord blood transplantation, or HLA-matched related donor bone marrow transplantation and granulocyte colony-stimulating factor administration.

Drug: cyclophosphamideDrug: cyclosporineDrug: FludarabineDrug: mycophenolate mofetilRadiation: total marrow irradiationProcedure: umbilical cord blood transplantationBiological: Granulocyte colony-stimulating factorBiological: HLA-matched related donor bone marrow

Interventions

cyclophosphamideDRUG

60 mg/kg/day intravenous x 2 days pre-transplant, total dose 120 mg/kg

Also known as: Cytoxan
Cohort -1Cohort 1Cohort 2Cohort 3Cohort 4
cyclosporineDRUG

Beginning on Day -3 pre-transplant maintaining a level of \>200 ng/mL. CSA dosing will be monitored and altered as clinically appropriate by Pharm D or physician, and discontinue at approximately day + 180 post-transplant.

Also known as: CSA
Cohort -1Cohort 1Cohort 2Cohort 3Cohort 4
FludarabineDRUG

25 mg/m2/day intravenous as a 1 hour infusion for consecutive 3 days pre-transplant, total dose 75 mg/m2

Also known as: Fludara
Cohort -1Cohort 1Cohort 2Cohort 3Cohort 4
mycophenolate mofetilDRUG

Beginning on day -3, use intravenous route between days -3 and +5, followed by oral administration on Day +6 through +30, if tolerated. 15mg/kg/dose for patients \<40 kg, 3 gm/day for patients \>40 kg.

Also known as: MMF
Cohort -1Cohort 1Cohort 2Cohort 3Cohort 4
total marrow irradiationRADIATION

Dose escalating schedule per Cohort (TMI: 300 cGy) once daily.

Also known as: TMI
Cohort -1Cohort 1Cohort 2Cohort 3Cohort 4
umbilical cord blood transplantationPROCEDURE

product will be infused via intravenous drip on Day 0 according to current University of Minnesota guidelines for Umbilical Cord Blood Grafts

Also known as: umbilical cord blood, allogeneic hematopoietic stem cell transplantation
Cohort -1Cohort 1Cohort 2Cohort 3Cohort 4
Granulocyte colony-stimulating factorBIOLOGICAL

5 mcg/kg/day intravenous or subcutaneous based on body weight beginning on Day +1 after umbilical cord blood infusion until absolute neutrophil count exceeds 2.5 x 10\^9/L for 3 consecutive days.

Also known as: G-CSF
Cohort -1Cohort 1Cohort 2Cohort 3Cohort 4
HLA-matched related donor bone marrowBIOLOGICAL

Related donor bone marrow or mobilized stem cells will be collected (target cell dose 5x10\^8 nucleated cells/kg recipient weight, minimum 3x10\^8 nucleated cells/kg recipient weight) and infused without processing on day 0 according to University of Minnesota Blood and Marrow Transplant Program guidelines.

Also known as: mobilized peripheral blood stem cells
Cohort -1Cohort 1Cohort 2Cohort 3Cohort 4

Eligibility Criteria

AgeUp to 55 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Acute lymphoblastic leukemia
  • ≥ Complete remission 2 (CR2) (adults ≥ 18 years and ≤ 55 years)
  • CR2 in pediatrics (defined as \<18 years) and \<12 months duration of first remission
  • ≥ CR3 or not in remission (pediatric patients \<18 years)
  • T cell leukemia ≥ CR2
  • Evidence of pre-transplant minimal residual disease (MRD) by flow cytometry, FISH or cytogenetics
  • Myelodysplastic syndrome
  • ≤ 55 years of age and ≥ 10% blasts, not responsive to hypomethylating agents and/or conventional therapy
  • Acute myeloid leukemia
  • Not in remission (pediatric patients \<18 years)
  • Not in remission (10-30% blasts in the bone marrow for adult patients ≥18 years and ≤ 55 years)
  • Evidence of pre-transplant minimal residual disease (MRD) by flow cytometry, FISH or cytogenetics
  • Multiple myeloma
  • No prior autologous transplant and fitting into one of the following disease categories:
  • Early disease stage (CR1/PR1) with high-risk molecular features
  • +16 more criteria

You may not qualify if:

  • Active uncontrolled infection at time of enrollment or documented fungal infection within 3 months.
  • Evidence of Human immunodeficiency virus (HIV) infection
  • Pregnant or breast feeding. The agents used in this study may be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy.
  • Prior myeloablative transplant within the last 6 months
  • Prior total body irradiation (TBI) making total marrow irradiation (TMI) not feasible

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

Precursor Cell Lymphoblastic Leukemia-LymphomaMyelodysplastic SyndromesMultiple MyelomaLeukemia, Myeloid, AcuteCongenital Abnormalities

Interventions

CyclophosphamideCyclosporinefludarabinefludarabine phosphateMycophenolic AcidCord Blood Stem Cell TransplantationGranulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Leukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesBone Marrow DiseasesNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic DisordersLeukemia, MyeloidCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsCyclosporinsPeptides, CyclicMacrocyclic CompoundsPolycyclic CompoundsPeptidesAmino Acids, Peptides, and ProteinsCaproatesAcids, AcyclicCarboxylic AcidsFatty AcidsLipidsStem Cell TransplantationCell TransplantationCell- and Tissue-Based TherapyBiological TherapyTherapeuticsTransplantationSurgical Procedures, OperativeColony-Stimulating FactorsGlycoproteinsGlycoconjugatesCarbohydratesHematopoietic Cell Growth FactorsCytokinesIntercellular Signaling Peptides and ProteinsProteinsBiological Factors

Study Officials

  • John Wagner, MD

    Masonic Cancer Center, University of Minnesota

    PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

First Submitted

May 29, 2008

First Posted

May 30, 2008

Study Start

August 1, 2012

Primary Completion

November 1, 2016

Study Completion

December 1, 2016

Last Updated

December 5, 2017

Record last verified: 2017-12

Locations

US(1)