NCT00054236

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Umbilical cord blood transplantation may be able to replace cells destroyed by chemotherapy. PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy followed by umbilical cord blood transplantation in treating patients who have hematologic cancer or severe aplastic anemia.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
55

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started May 2002

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

May 1, 2002

Completed
9 months until next milestone

First Submitted

Initial submission to the registry

February 5, 2003

Completed
1 day until next milestone

First Posted

Study publicly available on registry

February 6, 2003

Completed
8.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2011

Completed
Last Updated

July 27, 2020

Status Verified

July 1, 2020

Enrollment Period

8.8 years

First QC Date

February 5, 2003

Last Update Submit

July 23, 2020

Conditions

Chronic Myeloproliferative DisordersLeukemiaLymphomaMultiple Myeloma and Plasma Cell NeoplasmMyelodysplastic SyndromesMyelodysplastic/Myeloproliferative Diseases

Keywords

refractory anemia with excess blasts in transformationrefractory anemia with excess blastsadult acute myeloid leukemia in remissionchildhood acute myeloid leukemia in remissionrecurrent adult acute myeloid leukemiarecurrent childhood acute myeloid leukemiaadult erythroleukemia (M6a)childhood acute erythroleukemia (M6)adult acute minimally differentiated myeloid leukemia (M0)childhood acute minimally differentiated myeloid leukemia (M0)adult acute megakaryoblastic leukemia (M7)childhood acute megakaryocytic leukemia (M7)adult acute lymphoblastic leukemia in remissionchildhood acute lymphoblastic leukemia in remissionrecurrent adult acute lymphoblastic leukemiarecurrent childhood acute lymphoblastic leukemiaaccelerated phase chronic myelogenous leukemiachronic phase chronic myelogenous leukemiapreviously treated myelodysplastic syndromesrefractory chronic lymphocytic leukemiastage I multiple myelomastage II multiple myelomastage III multiple myelomarecurrent/refractory childhood Hodgkin lymphomapolycythemia veraprimary myelofibrosisessential thrombocythemiarefractory multiple myelomarecurrent grade 1 follicular lymphomarecurrent grade 2 follicular lymphomarecurrent grade 3 follicular lymphomarecurrent adult diffuse large cell lymphomarecurrent adult diffuse mixed cell lymphomarecurrent adult diffuse small cleaved cell lymphomarecurrent adult Burkitt lymphomarecurrent adult immunoblastic large cell lymphomarecurrent adult lymphoblastic lymphomarecurrent mantle cell lymphomarecurrent childhood large cell lymphomarecurrent childhood lymphoblastic lymphomarecurrent childhood small noncleaved cell lymphomachildhood diffuse large cell lymphomachildhood immunoblastic large cell lymphomaBurkitt lymphomaanaplastic large cell lymphomarecurrent adult Hodgkin lymphomachildhood chronic myelogenous leukemiachronic eosinophilic leukemiachronic neutrophilic leukemiamyelodysplastic/myeloproliferative disease, unclassifiableatypical chronic myeloid leukemiarecurrent marginal zone lymphomarecurrent small lymphocytic lymphomaextranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissuenodal marginal zone B-cell lymphomasplenic marginal zone lymphomaadult acute myeloid leukemia with t(8;21)(q22;q22)adult acute myeloid leukemia with t(16;16)(p13;q22)adult acute myeloid leukemia with inv(16)(p13;q22)adult acute myeloid leukemia with 11q23 (MLL) abnormalitiesadult acute myeloid leukemia with t(15;17)(q22;q12)childhood myelodysplastic syndromes

Outcome Measures

Primary Outcomes (1)

  • Event-free survival by disease assessment

    at 28 and 100 days and then at 6, 9, 12, 18, and 24 months

Secondary Outcomes (1)

  • Umbilical cord blood donor engraftment by chimerism and complete blood count (CBC)

    monthly for 6 months and then at 9, 12, 18, and 24 months

Study Arms (1)

non-myeloablative conditioning regimen

EXPERIMENTAL
Biological: anti-thymocyte globulinBiological: filgrastimDrug: cyclophosphamideDrug: fludarabine phosphateProcedure: umbilical cord blood transplantationDrug: methylprednisolone

Interventions

anti-thymocyte globulinBIOLOGICAL

anti-thymocyte globulin (ATG) IV over at least 4 hours on days -2 to -1

non-myeloablative conditioning regimen
filgrastimBIOLOGICAL

Patients receive filgrastim (G-CSF) subcutaneously beginning on day 7 and continuing until blood counts recover.

non-myeloablative conditioning regimen
cyclophosphamideDRUG

cyclophosphamide IV over 2 hours on days -3 to -2

non-myeloablative conditioning regimen
fludarabine phosphateDRUG

fludarabine IV over 30 minutes on days -8 to -4

non-myeloablative conditioning regimen
umbilical cord blood transplantationPROCEDURE

Patients undergo multiple unit umbilical cord blood transplantation on days 0-1.

non-myeloablative conditioning regimen
methylprednisoloneDRUG

Patients unable to tolerate ATG may receive methylprednisolone IV over 1 hour on days -3 to -1.

non-myeloablative conditioning regimen

Eligibility Criteria

AgeUp to 120 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
DISEASE CHARACTERISTICS: * One of the following histologically confirmed diagnoses: * Acquired severe aplastic anemia * Meets at least 2 of the following criteria: * Granulocyte count less than 500/mm\^3 * Platelet count less than 20,000/mm\^3 * Absolute reticulocyte count less than 20,000/mm\^3 (after correction for hematocrit) * Unresponsive to OR recurrent disease after prior treatment with anti-thymocyte globulin and/or cyclosporine * Acute myeloid leukemia (AML), meeting 1 of the following criteria: * Failed induction therapy * In first complete remission (CR) with any of the following high-risk features: * Stem cell or biphenotype classification (M0) * Erythroleukemia (M6) * Acute megakaryocytic leukemia (M7) * Cytogenetic markers indicative of poor prognosis * t(15;17) translocation and failed first-line induction therapy OR there is molecular evidence of persistent disease * t(8;21) and inv(16) translocations and failed first-line induction therapy * In early relapse\* * In second or subsequent remission * Recurrent disease after prior autologous stem cell transplantation (SCT) NOTE: \*No refractory relapse * Acute lymphoblastic leukemia, meeting 1 of the following criteria: * In early relapse\* * In second or subsequent remission * In first CR with the following high-risk features: * t(4;11) or t(9;22) translocation * Hyperleukocytosis (initial WBC greater than 30,000/mm\^3) * Failed to achieve CR by day 28 of standard induction therapy * Recurrent disease after prior autologous SCT NOTE: \*No refractory relapse * Chronic myelogenous leukemia * Chronic or accelerated phase that has failed medical management * Blastic phase allowed after reinduction chemotherapy induces chronic phase * Myelodysplastic syndromes meeting 1 of the following criteria: * Refractory to medical management * Presence of cytogenetic abnormalities predictive of transformation to acute leukemia, including the following: = 5q- = 7q- * Monosomy 7 and trisomy 8 * Evidence of evolution to AML (e.g., refractory anemia with excess blasts \[RAEB\], or RAEB in transformation) * Chronic lymphocytic leukemia * Refractory to treatment including fludarabine-based therapy * Recurrent disease after prior autologous SCT * Multiple myeloma * Recurrent disease after prior autologous SCT * Beyond first CR or failed induction therapy * Disease is sensitive to pretransplantation cytoreduction * Hodgkin's lymphoma * Beyond first CR or failed induction therapy * Disease is sensitive to pretransplantation cytoreduction * Non-Hodgkin's lymphoma (NHL) * Recurrent disease after prior autologous SCT * Beyond first CR or failed induction therapy * Disease is sensitive to pretransplantation cytoreduction * Mantle zone NHL allowed after induction therapy * Myeloproliferative disorders * Refractory to medical management * Allografting required unless grade 3 or greater myelofibrosis by bone marrow biopsy * No HLA-matched sibling donor available * Ineligible for a myeloablative conditioning regimen due to advanced age (over 55), extensive prior therapy, and/or other comorbidities * If under age 55, must meet at least 1 of the following criteria: * Received extensive prior therapy * Organ toxicity or infection precluding eligibility for allogeneic transplantation with full ablation conditioning * Availability of 2-5 umbilical cord blood units that are at least a 4/6 HLA match * No active CNS disease * No primary or grade 3 or 4 myelofibrosis PATIENT CHARACTERISTICS: Age * Any age Performance status * Karnofsky 70-100% (for patients 16 years of age and older) * Lansky 50-100% (for patients under 16 years of age) Life expectancy * At least 3 months Hematopoietic * See Disease Characteristics Hepatic * ALT/AST less than 4 times normal * Bilirubin less than 2.0 mg/dL (unless due to hepatic infiltration by primary malignancy) Renal * Creatinine clearance greater than 40 mL/min Cardiovascular * Shortening fraction or ejection fraction greater than 40% of normal value for age by echocardiogram or radionuclide scan Pulmonary * FVC and FEV\_1 greater than 60% of predicted * DLCO greater than 60% of predicted (adult patients) * Clearance by pulmonologist required if patient cannot perform pulmonary function tests Other * Not pregnant or nursing * No uncontrolled active infection (viral, bacterial, or fungal) * HIV negative PRIOR CONCURRENT THERAPY: Biologic therapy * See Disease Characteristics * More than 3 months since prior autologous stem cell transplantation Chemotherapy * See Disease Characteristics * At least 4 weeks since prior chemotherapy Endocrine therapy * Not specified Radiotherapy * Not specified Surgery * Not specified Other * Recovered from prior therapy * No other concurrent investigational agents that would preclude study participation or increase risk to patient * Investigational diagnostic procedures allowed

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

Study Sites (1)

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

MeSH Terms

Conditions

Myeloproliferative DisordersLeukemiaLymphomaMultiple MyelomaNeoplasms, Plasma CellMyelodysplastic SyndromesMyelodysplastic-Myeloproliferative DiseasesAnemia, Refractory, with Excess of BlastsLeukemia, Myeloid, AcuteLeukemia, Erythroblastic, AcuteLeukemia, Megakaryoblastic, AcutePrecursor Cell Lymphoblastic Leukemia-LymphomaLeukemia, Myeloid, Accelerated PhaseLeukemia, Myeloid, Chronic-PhaseLeukemia, Lymphocytic, Chronic, B-CellRecurrencePolycythemia VeraPrimary MyelofibrosisThrombocythemia, EssentialLymphoma, FollicularLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinBurkitt LymphomaLymphoma, Large-Cell, ImmunoblasticLymphoma, Mantle-CellDendritic Cell Sarcoma, InterdigitatingLymphoma, Large-Cell, AnaplasticHodgkin DiseasePdgfra-Associated Chronic Eosinophilic LeukemiaLeukemia, Neutrophilic, ChronicLeukemia, Myeloid, Chronic, Atypical, BCR-ABL NegativeLymphoma, B-Cell, Marginal ZoneCongenital Abnormalities

Interventions

Antilymphocyte SerumFilgrastimCyclophosphamidefludarabine phosphateCord Blood Stem Cell TransplantationMethylprednisolone

Condition Hierarchy (Ancestors)

Bone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic DisordersAnemia, RefractoryAnemiaLeukemia, MyeloidLeukemia, LymphoidLeukemia, Myelogenous, Chronic, BCR-ABL PositiveChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLeukemia, B-CellBone Marrow NeoplasmsHematologic NeoplasmsNeoplasms by SiteBlood Coagulation DisordersThrombocytosisBlood Platelet DisordersLymphoma, B-CellEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsHistiocytic Disorders, MalignantHistiocytosisLymphoma, T-CellCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Immune SeraAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsBiological ProductsComplex MixturesGranulocyte Colony-Stimulating FactorColony-Stimulating FactorsGlycoproteinsGlycoconjugatesCarbohydratesHematopoietic Cell Growth FactorsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesBiological FactorsPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsStem Cell TransplantationCell TransplantationCell- and Tissue-Based TherapyBiological TherapyTherapeuticsTransplantationSurgical Procedures, OperativePrednisolonePregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic Compounds

Study Officials

  • Brenda Cooper, MD

    Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive 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

February 5, 2003

First Posted

February 6, 2003

Study Start

May 1, 2002

Primary Completion

March 1, 2011

Study Completion

March 1, 2011

Last Updated

July 27, 2020

Record last verified: 2020-07

Locations

US(1)