NCT00577278

Brief Summary

RATIONALE: Giving monoclonal antibody therapy, radioimmunotherapy, and chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the stem cells from a related donor that do not exactly match the patient's blood, 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 also make an immune response against the body's normal cells. Giving tacrolimus and sirolimus before and after transplant may stop this from happening. PURPOSE: This phase II trial is studying the side effects and how well giving indium In 111 ibritumomab tiuxetan and yttrium y 90 ibritumomab tiuxetan together with rituximab, fludarabine, melphalan, and donor stem cell transplant works in treating patients with B-cell non-Hodgkin lymphoma.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
41

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Oct 2007

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

Study Start

First participant enrolled

October 3, 2007

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

December 19, 2007

Completed
1 day until next milestone

First Posted

Study publicly available on registry

December 20, 2007

Completed
11.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 30, 2019

Completed
3.6 years until next milestone

Results Posted

Study results publicly available

December 23, 2022

Completed
12 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 14, 2023

Completed
Last Updated

February 16, 2024

Status Verified

February 1, 2024

Enrollment Period

11.7 years

First QC Date

December 19, 2007

Results QC Date

November 28, 2022

Last Update Submit

February 13, 2024

Conditions

Graft Versus Host DiseaseLeukemiaLymphoma

Keywords

graft versus host diseasecontiguous stage II grade 1 follicular lymphomacontiguous stage II grade 2 follicular lymphomacontiguous stage II grade 3 follicular lymphomanoncontiguous stage II grade 1 follicular lymphomanoncontiguous stage II grade 2 follicular lymphomanoncontiguous stage II grade 3 follicular lymphomarecurrent grade 1 follicular lymphomarecurrent grade 2 follicular lymphomarecurrent grade 3 follicular lymphomastage I grade 1 follicular lymphomastage I grade 2 follicular lymphomastage I grade 3 follicular lymphomastage III grade 1 follicular lymphomastage III grade 2 follicular lymphomastage III grade 3 follicular lymphomastage IV grade 1 follicular lymphomastage IV grade 2 follicular lymphomastage IV grade 3 follicular lymphomacontiguous stage II adult diffuse large cell lymphomanoncontiguous stage II adult diffuse large cell lymphomarecurrent adult diffuse large cell lymphomastage I adult diffuse large cell lymphomastage III adult diffuse large cell lymphomastage IV adult diffuse large cell lymphomaWaldenstrom macroglobulinemiacontiguous stage II marginal zone lymphomaextranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissuenodal marginal zone B-cell lymphomanoncontiguous stage II marginal zone lymphomarecurrent marginal zone lymphomastage I marginal zone lymphomastage III marginal zone lymphomastage IV marginal zone lymphomaB-cell chronic lymphocytic leukemiarefractory chronic lymphocytic leukemiastage I chronic lymphocytic leukemiastage II chronic lymphocytic leukemiastage III chronic lymphocytic leukemiastage IV chronic lymphocytic leukemiacontiguous stage II mantle cell lymphomanoncontiguous stage II mantle cell lymphomarecurrent mantle cell lymphomastage I mantle cell lymphomastage III mantle cell lymphomastage IV mantle cell lymphomacontiguous stage II adult diffuse mixed cell lymphomanoncontiguous stage II adult diffuse mixed cell lymphomarecurrent adult diffuse mixed cell lymphomastage I adult diffuse mixed cell lymphomastage III adult diffuse mixed cell lymphomastage IV adult diffuse mixed cell lymphomacontiguous stage II small lymphocytic lymphomanoncontiguous stage II small lymphocytic lymphomarecurrent small lymphocytic lymphomastage I small lymphocytic lymphomastage III small lymphocytic lymphomastage IV small lymphocytic lymphoma

Outcome Measures

Primary Outcomes (1)

  • Relapse/Progression Rate at Two Years

    The primary endpoint was 2-year cumulative incidence of relapse/progression (RP), defined as time from alloHCT to disease recurrence or progression. Cumulative incidences for RP was generated in a competing-risk setting, given that death events were competing events.

    From the initial treatment to the last disease assessment, up to two years

Secondary Outcomes (2)

  • Overall Survival at Two Years

    From the initial treatment to the last disease assessment, up to two years

  • Progression-free Survival at Two Years

    From the initial treatment to the last disease assessment, up to two years

Study Arms (1)

Treatment (chemo, monoclonal antibody therapy, transplant)

EXPERIMENTAL

REDUCED-INTENSITY CONDITIONING: Patients receive rituximab IV followed by indium In-111 ibritumomab tiuxetan IV over 10 minutes on day -21 and rituximab IV followed by yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day -14. Patients also receive fludarabine phosphate IV on days -9 to -5 and melphalan IV on day -4. STEM CELL TRANSPLANTATION: Patients undergo APBSCT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO and sirolimus PO beginning on day -3 and continuing for up to 6 months with taper.

Biological: rituximabDrug: fludarabine phosphateDrug: melphalanDrug: sirolimusDrug: tacrolimusProcedure: allogeneic hematopoietic stem cell transplantationRadiation: indium In 111 ibritumomab tiuxetanRadiation: yttrium Y 90 ibritumomab tiuxetanOther: laboratory biomarker analysis

Interventions

rituximabBIOLOGICAL

Given IV

Also known as: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan
Treatment (chemo, monoclonal antibody therapy, transplant)
fludarabine phosphateDRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, Fludara
Treatment (chemo, monoclonal antibody therapy, transplant)
melphalanDRUG

Given IV

Also known as: Alkeran, CB-3025, L-PAM, L-phenylalanine mustard, L-Sarcolysin
Treatment (chemo, monoclonal antibody therapy, transplant)
sirolimusDRUG

Given PO

Also known as: AY 22989, Rapamune, rapamycin, SLM
Treatment (chemo, monoclonal antibody therapy, transplant)
tacrolimusDRUG

Given PO or IV

Also known as: FK 506, Prograf
Treatment (chemo, monoclonal antibody therapy, transplant)
allogeneic hematopoietic stem cell transplantationPROCEDURE

Undergo APBSCT

Treatment (chemo, monoclonal antibody therapy, transplant)
indium In 111 ibritumomab tiuxetanRADIATION

Given IV

Also known as: IDEC-In2B8
Treatment (chemo, monoclonal antibody therapy, transplant)
yttrium Y 90 ibritumomab tiuxetanRADIATION

Given IV

Also known as: 90Y ibritumomab tiuxetan, IDEC Y2B8, Y90 Zevalin, Y90-labeled ibritumomab tiuxetan
Treatment (chemo, monoclonal antibody therapy, transplant)
laboratory biomarker analysisOTHER

Correlative Studies

Treatment (chemo, monoclonal antibody therapy, transplant)

Eligibility Criteria

Age18 Years - 69 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • /6/human leukocyte antigen (HLA) matched sibling donor or related donor, or acceptable matched unrelated donor
  • Biopsy (Bx) proven diagnosis of LG (including small lymphocytic lymphoma \[SLL\]/chronic lymphocytic leukemia \[CLL\], lymphoplasmacytic lymphoma, marginal zone, mucosa-associated lymphoid tissue \[MALT\] lymphoma and follicular lymphoma \[FL\] grade 1 and 2), IG (FL grade 3 and DLCL) or MCL NHL
  • Prior demonstrated monoclonal CD20+ malignant B-Cell population in lymph nodes and/or BM Bx specimen
  • LG NHL; must have relapsed after achieving a complete response (CR) or partial response (PR) to prior therapy or have never responded to prior therapy, including chemotherapy and/or MAb therapy
  • MCL NHL in any disease state
  • Other aggressive B-cell lymphomas (excluding Burkitt lymphoma or Burkitt-like lymphoma) having had at least one relapse or having been refractory to chemotherapy
  • Bone marrow (BM) aspiration and Bx ( =\< 42 days prior to imaging dose) which show \< 25% lymphomatous involvement of total cellularity; in CLL, peripheral lymphocyte count \< 5000/mm\^3
  • Salvage chemotherapy/MAbs to reduce BM lymphomatous involvement and reduce disease bulk allowed
  • Normal renal function test with serum creatinine of =\< 1.5 mg/dl, or a creatinine clearance of \>= 60 ml/min
  • Adequate pulmonary function as measured by forced expiratory volume in one second (FEV1) \> 65% of predicted measured, or a diffusing capacity of carbon monoxide (DLCO) \>= 50% of predicted measured
  • Cardiac Ejection fraction of \> 50% by Echocardiogram (ECHO) or multi gated acquisition (MUGA)
  • Adequate liver function tests with a bilirubin of =\< 1.5 x normal and serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) =\< 2 x normal
  • Negative Human Immunodeficiency Virus (HIV) antibody
  • Karnofsky Performance Status (KPS) \> 80
  • No active Central Nervous System (CNS) disease or prior history of CNS disease
  • +6 more criteria

You may not qualify if:

  • Presence of Human Anti-Zevalin Antibody (HAZA)
  • Prior radioimmunotherapy (RIT)
  • Prior AHSCT; but prior aHSCT is allowed; prior fractionated total body irradiation (FTBI) in the conditioning regimen will be evaluated on an individual basis
  • Prior malignancy, except for: adequately treated basal cell or squamous cell skin cancer; adequately treated noninvasive carcinomas; or other cancer from which the patient has been disease-free for at least 5 years; myelodysplastic syndromes (MDS) is excluded from this criterion
  • Active evidence of Hepatitis B or C infection; hepatitis B surface antigen positive
  • Total peripheral lymphocyte count \> 5,000/mm\^3 if SLL/CLL
  • Burkitt lymphoma or Burkitt-like lymphoma
  • DONOR: Age \< 12 years
  • DONOR: Identical twin
  • DONOR: Pregnancy
  • DONOR: HIV infection
  • DONOR: Inability to achieve adequate venous access
  • DONOR: Known allergy to G-CSF
  • DONOR: Current serious systemic illness or any disease that may preclude the use of G-CSF (eg, recent thromboembolic event); for unrelated donors, considered ineligible by National Marrow Donor Program (NMDP) donor evaluation center

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010-3000, United States

Location

Related Publications (1)

  • Mei M, Palmer J, Tsai NN, Simpson J, O'Hearn J, Stein A, Forman S, Spielberger R, Cai JL, Htut M, Nakamura R, Al Malki MM, Herrera A, Wong J, Nademanee A. Results of a Phase II Trial of Allogeneic Hematopoietic Stem Cell Transplantation Using 90Y-Ibritumomab Tiuxetan (Zevalin) in Combination With Fludarabine and Melphalan in Patients With High-Risk B-Cell Non-Hodgkin's Lymphoma. Clin Lymphoma Myeloma Leuk. 2023 Sep;23(9):e268-e276. doi: 10.1016/j.clml.2023.05.011. Epub 2023 May 23.

    PMID: 37301631DERIVED

MeSH Terms

Conditions

Graft vs Host DiseaseLeukemiaLymphomaLymphoma, FollicularLymphoma, Large B-Cell, DiffuseWaldenstrom MacroglobulinemiaLymphoma, B-Cell, Marginal ZoneLeukemia, Lymphocytic, Chronic, B-CellLymphoma, Mantle-CellLymphoma, Non-Hodgkin

Interventions

Rituximabfludarabine phosphateMelphalanSirolimusTacrolimusIndiumibritumomab tiuxetan

Condition Hierarchy (Ancestors)

Immune System DiseasesNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersLymphoma, B-CellNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic DisordersLeukemia, B-CellLeukemia, LymphoidChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhenylalanineAmino Acids, AromaticAmino Acids, CyclicAmino AcidsMacrolidesLactonesMetals, HeavyElementsInorganic ChemicalsMetals

Results Point of Contact

Title
Dr. Matthew Mei
Organization
City of Hope Medical Center
mamei@coh.org
626-359-8111

Study Officials

  • Matthew Mei, MD

    City of Hope Medical 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

December 19, 2007

First Posted

December 20, 2007

Study Start

October 3, 2007

Primary Completion

May 30, 2019

Study Completion

December 14, 2023

Last Updated

February 16, 2024

Results First Posted

December 23, 2022

Record last verified: 2024-02

Locations

US(1)