Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by peripheral stem cell transplantation in treating patients who have hematologic cancer or aplastic anemia.

Trial Health

On Track

Trial Health Score

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

Enrollment

participants targeted

Target at P25-P50 for phase_2

Timeline

Completed

Started Jun 2000

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

11.3 years study duration

Study Start

First participant enrolled

June 1, 2000

Completed

4 months until next milestone

First Submitted

Initial submission to the registry

October 4, 2000

Completed

2.3 years until next milestone

First Posted

Study publicly available on registry

January 27, 2003

Completed

11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2004

Completed

7.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2011

Completed

Last Updated

December 8, 2011

Status Verified

December 1, 2011

Enrollment Period

3.6 years

First QC Date

October 4, 2000

Last Update Submit

December 7, 2011

Conditions

Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases Precancerous/Nonmalignant Condition Small Intestine Cancer Chronic Myeloproliferative Disorders

Keywords

monoclonal gammopathy of undetermined significancerecurrent childhood acute lymphoblastic leukemiarecurrent adult Hodgkin lymphomarecurrent cutaneous T-cell non-Hodgkin lymphomaisolated plasmacytoma of boneextramedullary plasmacytomarefractory multiple myelomaWaldenstrom macroglobulinemiarecurrent childhood lymphoblastic lymphomarecurrent childhood acute myeloid leukemiarecurrent adult acute myeloid leukemiarecurrent adult acute lymphoblastic leukemiarelapsing chronic myelogenous leukemiasmall intestine lymphomachronic phase chronic myelogenous leukemiaaccelerated phase chronic myelogenous leukemiablastic phase chronic myelogenous leukemiaadult acute myeloid leukemia in remissionadult acute lymphoblastic leukemia in remissionchildhood acute myeloid leukemia in remissionchildhood acute lymphoblastic leukemia in remissionpolycythemia verachronic idiopathic myelofibrosisessential thrombocythemiaadult acute erythroid leukemia (M6)adult acute megakaryoblastic leukemia (M7)childhood acute erythroleukemia (M6)childhood acute megakaryocytic leukemia (M7)recurrent/refractory childhood Hodgkin lymphomarefractory anemia with excess blastsrefractory anemia with excess blasts in transformationchronic myelomonocytic leukemiaacute undifferentiated leukemiarecurrent grade 1 follicular lymphomarecurrent grade 2 follicular lymphomarecurrent grade 3 follicular lymphomarecurrent adult diffuse small cleaved cell lymphomarecurrent adult diffuse mixed cell lymphomarecurrent adult diffuse large cell lymphomarecurrent adult immunoblastic large cell lymphomarecurrent adult lymphoblastic lymphomarecurrent adult Burkitt lymphomarecurrent adult T-cell leukemia/lymphomasecondary acute myeloid leukemiade novo myelodysplastic syndromespreviously treated myelodysplastic syndromessecondary myelodysplastic syndromesprolymphocytic leukemiaprimary systemic amyloidosisadult acute minimally differentiated myeloid leukemia (M0)childhood acute minimally differentiated myeloid leukemia (M0)recurrent childhood small noncleaved cell lymphomarecurrent childhood large cell lymphomarecurrent mantle cell lymphomaangioimmunoblastic T-cell lymphomaanaplastic large cell lymphomarecurrent mycosis fungoides/Sezary syndromechildhood chronic myelogenous leukemiachronic eosinophilic leukemiachronic neutrophilic leukemiaatypical chronic myeloid leukemiamyelodysplastic/myeloproliferative disease, unclassifiablejuvenile myelomonocytic 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)

Evaluation of Donor Engraftment
Peripheral blood from the donor and patient is obtained for chimerism studies. The primary analysis will consist of estimating the graft failure proportions for each of the separate patient groups and calculating confidence intervals for these proportions. This analysis will be done conditional on patients surviving at least 28 days.
at 28 days

Secondary Outcomes (2)

Stable donor hematopoietic chimerism
at day 100
Event free and overall survival
to progression/death

Interventions

anti-thymocyte globulinBIOLOGICAL

anti-thymocyte globulin IV over at least 4 hours on days -2 and -1

graft-versus-tumor induction therapyBIOLOGICAL

Patients undergo filgrastim (G-CSF)-mobilized allogeneic peripheral blood stem cell transplantation on day 0.

cyclophosphamideDRUG

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

fludarabine phosphateDRUG

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

peripheral blood stem cell transplantationPROCEDURE

Patients undergo filgrastim (G-CSF)-mobilized allogeneic peripheral blood stem cell transplantation on day 0.

Eligibility Criteria

AgeUp to 70 Years

Sexall

Healthy VolunteersNo

Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically proven high-risk hematologic malignancy * Acute non-lymphocytic leukemia (ANLL) after induction failure, or in first complete remission (CR) with high-risk features, including any of the following: * Stem cell or biphenotypic classification (AML-M0) * Erythroleukemia (AML-M6) * Acute megakaryocytic leukemia (AML-M7) * Cytogenetic markers indicative of poor prognosis * Failure to achieve CR after standard induction therapy * Acute lymphocytic leukemia (ALL) or ANLL in relapse or second or subsequent remission * Chronic myelogenous leukemia (CML) in chronic or accelerated phase * Patients with CML in blast crisis are eligible after reinduction chemotherapy places them in chronic phase * High-risk ALL in first CR with high risk defined by presence of t(4;11), t(9;22) translocation, hyperleukocytosis (initial WBC greater than 30,000/mm\^3), or failure to achieve CR by day 28 after standard induction * No T-cell ALL or t(8;14) positive B-cell ALL in first remission with hyperleukocytosis * Myelodysplastic syndrome by peripheral blood smear and bone marrow examination * Refractory to medical management OR * Cytogenetic abnormalities predictive of transformation into acute leukemia including 5q-, 7q-, monosomy 7, and trisomy 8 OR * Evidence of evolution to AML (e.g., refractory anemia with excess blasts (RAEB) or RAEB in transformation) * Multiple myeloma, non-Hodgkin's lymphoma (NHL), ANLL, or ALL with recurrent disease after autologous stem cell transplantation (SCT) * At least 3 months since prior autologous SCT * Hodgkin's lymphoma, NHL, or multiple myeloma beyond first CR or primary induction failures whose disease has demonstrated sensitivity to pre-transplantation cytoreduction (defined as greater than 50% reduction in tumor burden) * Mantle zone NHL allowed after induction therapy * Myeloproliferative disorder that is non-responsive to medical management and requires allografting, unless evidence of grade 3 or worse myelofibrosis on marrow biopsy OR * Histologically proven acquired severe aplastic anemia (SAA) that is recurrent or unresponsive after anti-thymocyte globulin and/or cyclosporine * SAA defined by at least 2 of the following conditions: * 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 * Ineligible for full ablative conditioning due to any of the following conditions: * Prior extensive therapy (more than 2 salvage chemotherapy regimens and/or autologous transplantation) * Over age 55 OR * Under age 55 with comorbid disease (e.g., suboptimal cardiac, pulmonary, or renal function and/or prior life-threatening infection) * HLA-A, B, and DR phenotypically identical sibling donor OR * HLA-A, B, and DR identical genetically matched unrelated donor * No ANLL in first CR (less than 5% blasts in marrow) with translocations t(8;21) and inv(16) unless failed first-line induction therapy OR * No ANLL in first CR (less than 5% blasts in marrow) with translocations t(15;17) abnormality unless failed first-line induction therapy OR molecular evidence of persistent disease * No active CNS disease PATIENT CHARACTERISTICS: Age: * 0 to 70 Performance status: * Zubrod 0-1 * Karnofsky 80-100% Life expectancy: * At least 3 months Hematopoietic: * See Disease Characteristics Hepatic: * ALT/AST no greater than 4 times normal * Bilirubin no greater than 2.0 mg/dL Renal: * See Disease Characteristics * Creatinine clearance at least 50 mL/min Cardiovascular: * See Disease Characteristics * Shortening fraction or ejection fraction at least 40% of normal for age by echocardiogram or radionuclide scan * No clinically significant comorbid illnesses (e.g., myocardial infarction or cerebrovascular accident) Pulmonary: * See Disease Characteristics * FVC and FEV\_1 at least 60% of predicted for age * DLCO at least 60% of predicted for adults Other: * No severe neurosensory symptoms (i.e., peripheral neuropathy) * HIV negative * Active infection allowed if controlled by appropriate drug therapy * Not pregnant or nursing * Negative pregnancy test PRIOR CONCURRENT THERAPY: Biologic therapy: * See Disease Characteristics Chemotherapy: * See Disease Characteristics Endocrine therapy: * Not specified Radiotherapy: * Not specified Surgery: * Not specified Other: * Recovered from prior therapy * No concurrent investigational agents unless approved by protocol investigators

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

Sponsors & Collaborators

Case Comprehensive Cancer Centerlead
National Cancer Institute (NCI)collaborator

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 DiseasesPrecancerous ConditionsMonoclonal Gammopathy of Undetermined SignificancePrecursor Cell Lymphoblastic Leukemia-LymphomaHodgkin DiseaseLymphoma, T-Cell, CutaneousWaldenstrom MacroglobulinemiaLeukemia, Myeloid, AcuteLeukemia, Myeloid, Chronic-PhaseLeukemia, Myeloid, Accelerated PhaseBlast CrisisPolycythemia VeraPrimary MyelofibrosisThrombocythemia, EssentialLeukemia, Erythroblastic, AcuteLeukemia, Megakaryoblastic, AcuteRecurrenceAnemia, Refractory, with Excess of BlastsLeukemia, Myelomonocytic, ChronicLeukemia, Biphenotypic, AcuteLymphoma, FollicularLymphoma, Non-HodgkinLymphoma, Large B-Cell, DiffuseLymphoma, Large-Cell, ImmunoblasticBurkitt LymphomaPrecursor T-Cell Lymphoblastic Leukemia-LymphomaLeukemia, ProlymphocyticImmunoglobulin Light-chain AmyloidosisDendritic Cell Sarcoma, InterdigitatingLymphoma, Mantle-CellImmunoblastic LymphadenopathyLymphoma, Large-Cell, AnaplasticMycosis FungoidesSezary SyndromePdgfra-Associated Chronic Eosinophilic LeukemiaLeukemia, Neutrophilic, ChronicLeukemia, Myeloid, Chronic, Atypical, BCR-ABL NegativeLeukemia, Myelomonocytic, JuvenileLymphoma, B-Cell, Marginal ZoneLeukemia, Lymphocytic, Chronic, B-CellCongenital Abnormalities

Interventions

Antilymphocyte SerumCyclophosphamidefludarabine phosphatePeripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Bone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic DisordersHypergammaglobulinemiaLeukemia, LymphoidLymphoma, T-CellLeukemia, MyeloidLeukemia, Myelogenous, Chronic, BCR-ABL PositiveChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsCell Transformation, NeoplasticCarcinogenesisNeoplastic ProcessesBone Marrow NeoplasmsHematologic NeoplasmsNeoplasms by SiteBlood Coagulation DisordersThrombocytosisBlood Platelet DisordersAnemia, RefractoryAnemiaLymphoma, B-CellEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsAmyloidosisProteostasis DeficienciesMetabolic DiseasesNutritional and Metabolic DiseasesHistiocytic Disorders, MalignantHistiocytosisLymphadenopathyLeukemia, B-CellCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Immune SeraAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsBiological ProductsComplex MixturesPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsHematopoietic Stem Cell TransplantationStem Cell TransplantationCell TransplantationCell- and Tissue-Based TherapyBiological TherapyTherapeuticsTransplantationSurgical Procedures, Operative

Study Officials

Tamila Kindwall-Keller, DO
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
PRINCIPAL INVESTIGATOR

Study Design

Study Type: interventional
Phase: phase 2
Allocation: NA
Masking: NONE
Purpose: TREATMENT
Intervention Model: SINGLE GROUP
Sponsor Type: OTHER
Responsible Party: SPONSOR

Study Record Dates

First Submitted

October 4, 2000

First Posted

January 27, 2003

Study Start

June 1, 2000

Primary Completion

January 1, 2004

Study Completion

October 1, 2011

Last Updated

December 8, 2011

Record last verified: 2011-12

Locations

US(1)

Brief Summary

Trial Health

Trial Health Score

Trial Relationships

Related Scientific Literature

Study Timeline

Study Start

First Submitted

First Posted

Primary Completion

Study Completion

Conditions

Keywords

Outcome Measures

Primary Outcomes (1)

Secondary Outcomes (2)

Interventions

Eligibility Criteria

Sponsors & Collaborators

Study Sites (1)

MeSH Terms

Conditions

Interventions

Condition Hierarchy (Ancestors)

Intervention Hierarchy (Ancestors)

Study Officials

Study Design

Study Record Dates

Locations