NCT00425802

Brief Summary

RATIONALE: Giving low doses of chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. Also, monoclonal antibodies, such as rituximab, can find cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. The donated stem cells may replace the patient's immune 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 rituximab before transplant and cyclosporine and mycophenolate mofetil after transplant may stop this from happening. PURPOSE: This phase II trial is studying the side effects and how well giving chemotherapy and radiation therapy together with rituximab and donor stem cell transplant works in treating patients with B-cell non-Hodgkin's lymphoma or chronic lymphocytic leukemia.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
61

participants targeted

Target at P50-P75 for phase_2 leukemia

Timeline
Completed

Started Nov 2006

Longer than P75 for phase_2 leukemia

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

November 28, 2006

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

January 19, 2007

Completed
4 days until next milestone

First Posted

Study publicly available on registry

January 23, 2007

Completed
9.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 28, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 28, 2016

Completed
1 year until next milestone

Results Posted

Study results publicly available

October 31, 2017

Completed
Last Updated

October 31, 2017

Status Verified

February 1, 2017

Enrollment Period

9.9 years

First QC Date

January 19, 2007

Results QC Date

August 11, 2017

Last Update Submit

October 24, 2017

Conditions

LeukemiaLymphoma

Keywords

noncontiguous stage II adult diffuse large cell lymphomarecurrent adult diffuse large cell lymphomastage III adult diffuse large cell lymphomastage IV adult diffuse large cell lymphomaB-cell chronic lymphocytic leukemiarefractory chronic lymphocytic leukemiastage III chronic lymphocytic leukemiastage IV chronic lymphocytic leukemianoncontiguous stage II mantle cell lymphomarecurrent mantle cell lymphomastage III mantle cell lymphomastage IV mantle cell lymphomanoncontiguous stage II grade 1 follicular lymphomanoncontiguous stage II grade 2 follicular lymphomarecurrent grade 1 follicular lymphomarecurrent grade 2 follicular lymphomastage III grade 1 follicular lymphomastage III grade 2 follicular lymphomastage IV grade 1 follicular lymphomastage IV grade 2 follicular lymphomanoncontiguous stage II small lymphocytic lymphomarecurrent small lymphocytic lymphomastage III small lymphocytic lymphomastage IV small lymphocytic lymphomanoncontiguous stage II marginal zone lymphomarecurrent marginal zone lymphomasplenic marginal zone lymphomastage III marginal zone lymphomastage IV marginal zone lymphomanoncontiguous stage II adult immunoblastic large cell lymphomastage III adult immunoblastic large cell lymphomastage IV adult immunoblastic large cell lymphomaextranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissuenodal marginal zone B-cell lymphomarecurrent adult immunoblastic large cell lymphoma

Outcome Measures

Primary Outcomes (1)

  • Overall Survival at 1 Year

    1 year

Secondary Outcomes (8)

  • Time to Neutrophil Engraftment

    2 years

  • Time to Platelet Engraftment

    1 year

  • Incidence of Moderate to Severe Grades II to IV Graft Versus Host Disease (GVHD) at 100 Days

    100 days

  • Incidence of Chronic GVHD at 1 Year

    1 year

  • Immune Reconstruction/CD4+ Count at 3 Months

    3 months

  • +3 more secondary outcomes

Study Arms (1)

treatment

OTHER

This is a phase 2 study of a treatment regimen consisting of a non-myeloablative (NMA) conditioning regimen incorporating low dose chemotherapy and low dose radiation as well as peri-transplant Rituximab and the transplantation of peripheral blood stem cells (PBSC) or bone marrow if PBSC collection not possible from an HLA compatible related or unrelated donor in patients with B cell lymphoid malignancies including diffuse large cell (DLC) and mantle cell non-Hodgkin's lymphoma (NHL), indolent B cell NHL, or chronic lymphocytic leukemia (CLL).

Biological: anti-thymocyte globulinBiological: filgrastimBiological: graft-versus-tumor induction therapyBiological: rituximabDrug: cyclophosphamideDrug: cyclosporineDrug: fludarabine phosphateDrug: mycophenolate mofetilProcedure: nonmyeloablative allogeneic hematopoietic stem cell transplantationRadiation: total-body irradiation

Interventions

anti-thymocyte globulinBIOLOGICAL
treatment
filgrastimBIOLOGICAL
treatment
graft-versus-tumor induction therapyBIOLOGICAL
treatment
rituximabBIOLOGICAL
treatment
cyclophosphamideDRUG
treatment
cyclosporineDRUG
treatment
fludarabine phosphateDRUG
treatment
mycophenolate mofetilDRUG
treatment
nonmyeloablative allogeneic hematopoietic stem cell transplantationPROCEDURE
treatment
total-body irradiationRADIATION
treatment

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
DISEASE CHARACTERISTICS: * Diagnosis of 1 of the following: * CD20-positive aggressive B-cell non-Hodgkin's lymphoma (NHL), including any of the following subtypes: * Diffuse large cell lymphoma\*, meeting 1 of the following criteria: * Relapsed disease after initial therapy, but failed to mobilize or had bone marrow involvement and therefore is not suitable for an autologous stem cell transplantation * High-intermediate- or high-risk second-line, age-adjusted International Prognostic Index score and in second complete remission (CR) or partial remission (PR) after autologous stem cell transplantation * Failed prior autologous stem cell transplantation and in PR or better after salvage chemotherapy * Large cell transformation of indolent NHL or chronic lymphocytic leukemia (CLL), meeting the following criteria: * In CR or PR of the large cell component of disease after salvage chemotherapy or autologous stem cell transplantation * Mantle cell lymphoma\*, meeting 1 of the following criteria: * High-risk disease (e.g., p53 positivity) and in first CR or PR after initial therapy * Relapsed disease after initial therapy and in second or third CR or PR after salvage chemotherapy NOTE: \*No progressive disease at allograft work-up * CD20-positive indolent NHL (e.g., follicular lymphoma, small cell lymphoma, or marginal zone NHL) OR CLL * Second or subsequent progression (pre-allograft cytoreduction necessary, but CR or PR not required) * Relapsed disease must be biopsy-proven * Must have received pre-allograft salvage chemotherapy, including 1 of the following: * Single autologous stem cell transplantation using high-dose chemotherapy conditioning within the past 120 days * At least 2 courses of intensive combination chemotherapy (e.g., RICE \[rituximab, ifosfamide, carboplatin, etoposide\]), according to diagnosis, within the past 80 days * CLL patients who have received CAMPATH do not have to receive pre-allograft salvage chemotherapy * HLA-compatible related or unrelated donor available * HLA-matched ≥ 9/10 of the A, B, C, DRB1, and DQB1 loci, as tested by high resolution typing * One allele mismatch allowed PATIENT CHARACTERISTICS: * Karnofsky performance status 70-100% * Creatinine \< 1.2 mg/mL OR creatinine clearance ≥ 50 mL/min * Bilirubin \< 2.5 mg/dL * AST and ALT ≤ 3 times upper limit of normal (unless benign congenital hyperbilirubinemia is present) * Spirometry and corrected DLCO ≥ 50% of normal * LVEF ≥ 40% * Albumin ≥ 2.5 g/dL * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No active uncontrolled infection, including active infection with Aspergillus or other mold * No HIV infection * No hepatitis B antibody or antigen positivity PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior allogeneic transplantation

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

Sponsors & Collaborators

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

  • Sauter CS, Lechner L, Scordo M, Zheng J, Devlin SM, Fleming SE, Castro-Malaspina H, Moskowitz CH. Pretransplantation fluorine-18-deoxyglucose--positron emission tomography scan lacks prognostic value in chemosensitive B cell non-hodgkin lymphoma patients undergoing nonmyeloablative allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2014 Jun;20(6):881-4. doi: 10.1016/j.bbmt.2014.02.009. Epub 2014 Feb 15.

    PMID: 24534109DERIVED

Related Links

MeSH Terms

Conditions

LeukemiaLymphomaLymphoma, Large B-Cell, DiffuseLeukemia, Lymphocytic, Chronic, B-CellLymphoma, Mantle-CellLymphoma, FollicularLymphoma, B-Cell, Marginal ZoneLymphoma, Large-Cell, Immunoblastic

Interventions

Antilymphocyte SerumFilgrastimRituximabCyclophosphamideCyclosporinefludarabine phosphateMycophenolic AcidWhole-Body Irradiation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLymphoma, B-CellLymphoma, Non-HodgkinLeukemia, B-CellLeukemia, LymphoidChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

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 FactorsAntibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsCyclosporinsPeptides, CyclicMacrocyclic CompoundsPolycyclic CompoundsCaproatesAcids, AcyclicCarboxylic AcidsFatty AcidsLipidsRadiotherapyTherapeuticsInvestigative Techniques

Results Point of Contact

Title
Hugo Castro-Malaspina, MD
Organization
Memorial Sloan Kettering Cancer Center
castro-h@mskcc.org
212-639-8197

Study Officials

  • Hugo R. Castro-Malaspina, MD

    Memorial Sloan Kettering Cancer Center

    PRINCIPAL INVESTIGATOR

  • Juliet Barker, MBBS

    Memorial Sloan Kettering Cancer Center

    PRINCIPAL INVESTIGATOR

  • Craig Moskowitz, MD

    Memorial Sloan Kettering Cancer Center

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

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

January 19, 2007

First Posted

January 23, 2007

Study Start

November 28, 2006

Primary Completion

October 28, 2016

Study Completion

October 28, 2016

Last Updated

October 31, 2017

Results First Posted

October 31, 2017

Record last verified: 2017-02

Locations

US(1)