NCT00134004

Brief Summary

RATIONALE: Giving low doses of chemotherapy, such as fludarabine and cyclophosphamide, and radiation therapy before a donor bone marrow transplant helps stop the growth of cancer cells. Giving chemotherapy or radiation therapy before or after transplant also stops the patient's immune system from rejecting the donor's bone marrow stem cells. The donated stem cells may replace the patient's immune system cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and mycophenolate mofetil after the transplant may stop this from happening. PURPOSE: This phase II trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation works in treating patients who are undergoing a donor bone marrow transplant for hematologic cancer.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
210

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Oct 2004

Longer than P75 for phase_2

Geographic Reach
1 country

3 active sites

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

October 1, 2004

Completed
11 months until next milestone

First Submitted

Initial submission to the registry

August 22, 2005

Completed
2 days until next milestone

First Posted

Study publicly available on registry

August 24, 2005

Completed
9.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2015

Completed
8 months until next milestone

Results Posted

Study results publicly available

August 24, 2015

Completed
Last Updated

October 6, 2015

Status Verified

September 1, 2015

Enrollment Period

10.3 years

First QC Date

August 22, 2005

Results QC Date

June 26, 2015

Last Update Submit

September 2, 2015

Conditions

Chronic Myeloproliferative DisordersLeukemiaLymphomaMultiple Myeloma and Plasma Cell NeoplasmMyelodysplastic Syndromes

Keywords

adult acute lymphoblastic leukemia in remissionadult acute myeloid leukemia in remissionchildhood acute lymphoblastic leukemia in remissionchildhood acute myeloid leukemia in remissionchildhood chronic myelogenous leukemiachronic phase chronic myelogenous leukemiarefractory chronic lymphocytic leukemiaextranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissueadult 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)chronic idiopathic myelofibrosischronic myelomonocytic leukemiade novo myelodysplastic syndromespreviously treated myelodysplastic syndromesnoncontiguous stage II adult Burkitt lymphomanoncontiguous stage II adult diffuse large cell lymphomanoncontiguous stage II adult diffuse mixed cell lymphomanoncontiguous stage II adult diffuse small cleaved cell lymphomanoncontiguous stage II adult immunoblastic large cell lymphomanoncontiguous stage II adult lymphoblastic lymphomanoncontiguous stage II grade 1 follicular lymphomanoncontiguous stage II grade 2 follicular lymphomanoncontiguous stage II grade 3 follicular lymphomanoncontiguous stage II mantle cell lymphomanoncontiguous stage II marginal zone lymphomanoncontiguous stage II small lymphocytic lymphomarecurrent adult Burkitt lymphomarecurrent adult diffuse large cell lymphomarecurrent adult diffuse mixed cell lymphomarecurrent adult diffuse small cleaved cell lymphomarecurrent adult Hodgkin lymphomarecurrent adult immunoblastic large cell lymphomarecurrent adult lymphoblastic lymphomarecurrent/refractory childhood Hodgkin lymphomarecurrent childhood large cell lymphomarecurrent childhood lymphoblastic lymphomarecurrent childhood small noncleaved cell lymphomanodal marginal zone B-cell lymphomarecurrent grade 1 follicular lymphomarecurrent grade 2 follicular lymphomarecurrent grade 3 follicular lymphomarecurrent mantle cell lymphomarecurrent marginal zone lymphomarecurrent small lymphocytic lymphomarefractory multiple myelomarelapsing chronic myelogenous leukemiasecondary myelodysplastic syndromessplenic marginal zone lymphomastage I multiple myelomastage II multiple myelomastage III multiple myelomastage III adult Burkitt lymphomastage III adult diffuse large cell lymphomastage III adult diffuse mixed cell lymphomastage III adult diffuse small cleaved cell lymphomastage III adult Hodgkin lymphomastage III adult immunoblastic large cell lymphomastage III adult lymphoblastic lymphomastage III grade 1 follicular lymphomastage III grade 2 follicular lymphomastage III grade 3 follicular lymphomastage III mantle cell lymphomastage III marginal zone lymphomapolycythemia veraessential thrombocythemiastage III small lymphocytic lymphomastage IV mantle cell lymphomastage IV marginal zone lymphomastage IV grade 1 follicular lymphomastage IV grade 2 follicular lymphomastage IV grade 3 follicular lymphomastage IV adult Burkitt lymphomastage IV adult diffuse large cell lymphomastage IV adult diffuse mixed cell lymphomastage IV adult diffuse small cleaved cell lymphomastage IV adult immunoblastic large cell lymphomastage IV adult lymphoblastic lymphomastage IV small lymphocytic lymphomastage IV adult Hodgkin lymphomachildhood myelodysplastic syndromes

Outcome Measures

Primary Outcomes (3)

  • Transplant-related Mortality

    Percentage of participants who die for any reason other than recurrence of disease.

    Cumulative incidence for the entire study, up to 11 years

  • Relapse Rate

    Percentage of participants who experience disease relapse.

    Cumulative incidence for the entire study, up to 11 years

  • Progression-free Survival

    Percentage of participants who do not experience disease relapse, disease progression, or death.

    2 years

Secondary Outcomes (2)

  • Graft Failure Rate

    Cumulative incidence for the entire study, up to 11 years

  • Hematologic and Non-hematologic Toxicities as Measured by NCI Common Toxicity Criteria for Adverse Events, v 3.0 Weekly Until 1 Year After Transplantation

    1 year

Study Arms (1)

Mini-haplo Transplant

EXPERIMENTAL

Non-myeloablative haploidentical bone marrow transplant with a fludarabine, cyclophosphamide (Cy), TBI (total body irradiation) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis.

Drug: cyclophosphamideDrug: fludarabine phosphateDrug: mycophenolate mofetilDrug: tacrolimusProcedure: allogeneic bone marrow transplantationRadiation: radiation therapy

Interventions

cyclophosphamideDRUG
Mini-haplo Transplant
fludarabine phosphateDRUG
Mini-haplo Transplant
mycophenolate mofetilDRUG
Mini-haplo Transplant
tacrolimusDRUG
Mini-haplo Transplant
allogeneic bone marrow transplantationPROCEDURE
Mini-haplo Transplant
radiation therapyRADIATION
Mini-haplo Transplant

Eligibility Criteria

Age6 Months - 74 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
DISEASE CHARACTERISTICS: * Diagnosis of 1 of the following hematologic malignancies: * Acute leukemia * In second or subsequent complete remission (CR), as defined by absence of abnormal blast population by flow cytometry * In first CR with any of the following poor-risk cytogenetic features: * Alteration of chromosome 5 or 7 * Multiple abnormalities * Philadelphia chromosome positive * Chronic phase chronic myelogenous leukemia (CML) * In first chronic phase and refractory to interferon alfa or imatinib mesylate * In second or subsequent chronic phase * Chronic lymphocytic leukemia, meeting 1 of the following criteria: * Received prior chemotherapy with a nucleoside analog and had remission lasting \< 6 months * Received 1 prior therapy and has any of the following high-risk features: * Cytogenetic abnormalities of 17p, 11q * Mutations of the Zap70 gene * Somatically unmutated immunoglobulin heavy chain variable region genes * Hodgkin's lymphoma * Ineligible for autologous stem cell transplantation (SCT) due to any of the following exclusion factors: * LVEF \< 45% * FEV\_1 or FVC \< 50% of predicted (75% of predicted in patients with prior thoracic or mantle radiotherapy) * Total bilirubin \> 2.0 mg/dL (unless documented Gilbert's disease) * Creatinine \> 2.0 mg/dL * Non-Hodgkin's lymphoma (NHL) * Low-grade NHL allowed provided patient had a remission duration of \< 1 year after administration of any established, multi-agent chemotherapy regimen (e.g., CVP, CHOP, or rituximab in combination with CHOP) * Intermediate- or high-grade NHL allowed provided patient is ineligible for autologous SCT according to the criteria listed above * Multiple myeloma * Myelodysplastic syndromes * Paroxysmal nocturnal hemoglobinuria * Chronic myeloproliferative disorders other than CML, including any of the following: * Chronic myelomonocytic leukemia * Agnogenic myeloid metaplasia (or myeloid metaplasia with myelofibrosis), with hemoglobin \< 10 g/dL OR WBC \< 4,000/mm\^3 or \> 30,000/mm\^3 * Polycythemia vera or essential thrombocythemia in "spent" phase, with a history of 2 of the following: * Marrow fibrosis * Splenomegaly * Cytopenia (i.e., absolute neutrophil count \< 1,500/mm\^3, platelet count \< 100,000/mm\^3, hemoglobin \< 10 g/dL) * Polycythemia vera or essential thrombocythemia with transformation to myelodysplastic syndromes or acute myeloid leukemia (requires treatment to achieve \< 20% blasts in marrow) * No smoldering myeloma * Patients with acute myeloid leukemia or myelodysplastic syndromes must have had comprehensive cytogenetic evaluation of bone marrow specimen during active disease * Ineligible for or refused bone marrow transplantation from an HLA-matched sibling or unrelated donor * Ineligible for or refused autologous SCT * Must have an HLA mismatched (i.e., 3/6, 4/6, or 5/6) related (first-degree relative)\* donor available * Donor ≥ 18 years of age NOTE: \*Patients with an inherited recombinant HLA haplotype may receive marrow from the parent in whose gamete the recombination occurred NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology. PATIENT CHARACTERISTICS: Age * 6 months to 74 years Performance status * ECOG 0-1 Life expectancy * Not specified Hematopoietic * See Disease Characteristics Hepatic * See Disease Characteristics * Bilirubin \< 3.1 mg/dL Renal * See Disease Characteristics Cardiovascular * See Disease Characteristics * LVEF ≥ 35% Pulmonary * See Disease Characteristics * FEV\_1 or FVC ≥ 40% of predicted in patients without prior thoracic or mantle radiotherapy (60% of predicted in patients with prior thoracic or mantle radiotherapy) Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * HIV negative * Geographically accessible * No debilitating medical or psychiatric illness that would preclude giving informed consent or receiving optimal treatment or follow-up PRIOR CONCURRENT THERAPY: Biologic therapy * See Disease Characteristics * No prior transfusions from donor Chemotherapy * See Disease Characteristics Endocrine therapy * Not specified Radiotherapy * See Disease Characteristics Surgery * Not specified

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

Sponsors & Collaborators

Study Sites (3)

Blood and Marrow Transplant Program at Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

Hahnemann University Hospital

Philadelphia, Pennsylvania, 19102-1192, United States

Location

MeSH Terms

Conditions

Myeloproliferative DisordersLeukemiaLymphomaMultiple MyelomaNeoplasms, Plasma CellMyelodysplastic SyndromesLeukemia, Myeloid, Chronic-PhaseLeukemia, Lymphocytic, Chronic, B-CellCongenital AbnormalitiesPrimary MyelofibrosisLeukemia, Myelomonocytic, ChronicBurkitt LymphomaLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinHodgkin DiseaseLymphoma, Large-Cell, ImmunoblasticPrecursor Cell Lymphoblastic Leukemia-LymphomaRecurrenceDendritic Cell Sarcoma, InterdigitatingLymphoma, B-Cell, Marginal ZoneLymphoma, FollicularLymphoma, Mantle-CellPolycythemia VeraThrombocythemia, Essential

Interventions

Cyclophosphamidefludarabine phosphateMycophenolic AcidTacrolimusRadiotherapy

Condition Hierarchy (Ancestors)

Bone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic DisordersLeukemia, Myelogenous, Chronic, BCR-ABL PositiveLeukemia, MyeloidChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLeukemia, B-CellLeukemia, LymphoidCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesMyelodysplastic-Myeloproliferative DiseasesEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLymphoma, B-CellHistiocytic Disorders, MalignantHistiocytosisBone Marrow NeoplasmsHematologic NeoplasmsNeoplasms by SiteBlood Coagulation DisordersThrombocytosisBlood Platelet Disorders

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsCaproatesAcids, AcyclicCarboxylic AcidsFatty AcidsLipidsMacrolidesLactonesTherapeutics

Results Point of Contact

Title
Dr. Ephraim Fuchs
Organization
Johns Hopkins University
fuchsep@jhmi.edu
410-419-6479

Study Officials

  • Ephraim J. Fuchs, MD

    Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

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

August 22, 2005

First Posted

August 24, 2005

Study Start

October 1, 2004

Primary Completion

January 1, 2015

Study Completion

January 1, 2015

Last Updated

October 6, 2015

Results First Posted

August 24, 2015

Record last verified: 2015-09

Locations

US(3)