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Phase 2 Trial of Prophylactic Rituximab Therapy for Prevention of CGVHD

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ClinicalTrials.gov Identifier: NCT00186628
Recruitment Status : Completed
First Posted : September 16, 2005
Results First Posted : November 28, 2017
Last Update Posted : November 28, 2017
Sponsor:
Collaborators:
The Leukemia and Lymphoma Society
National Cancer Institute (NCI)
Information provided by (Responsible Party):
David Miklos, Stanford University

September 14, 2005
September 16, 2005
December 12, 2016
November 28, 2017
November 28, 2017
June 2005
November 2010   (Final data collection date for primary outcome measure)
Chronic Graft-vs-Host Disease (cGvHD) [ Time Frame: 4 years ]
The cumulative percentage of participants who develop chronic graft-vs-host disease (cGvHD). Chronic cGvHD was defined as at least one instance of a clinically-accepted marker for cGvHD (see Filipovich, et al. Biology of Blood and Marrow Transplantation. 2005;11:945-955)
Chronic GVHD
Complete list of historical versions of study NCT00186628 on ClinicalTrials.gov Archive Site
  • Incidence of Relapse [ Time Frame: 4 years ]
    Subjects who Relapsed following after Allogeneic HSCT
  • Mortality [ Time Frame: Day 100 and 1 year ]
    Number of participants who died within 100 days and within 1 year, non-relapse and associated with relapse.
  • Overall Survival [ Time Frame: 4 years ]
Relapse, non-relapse mortality
Not Provided
Not Provided
 
Phase 2 Trial of Prophylactic Rituximab Therapy for Prevention of CGVHD
An Open-label, Phase 2 Trial of Prophylactic Rituximab Therapy for Prevention of Chronic Graft Versus Host Disease After TLI/ARG Nonmyeloablative Allogeneic Stem Cell Transplantation
To determine if rituximab administered after allogeneic transplantation decreases the incidence of chronic graft-vs-host disease (cGvHD)
To test if prophylactic anti-B-cell therapy (weekly rituximab) given within 60 to 90 days after allogeneic transplantation will decrease allogeneic donor B-cell immunity and possibly the incidence of chronic graft-vs-host disease (cGvHD).
Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Leukemia, Mast-Cell
  • Mantle-cell Lymphoma
  • Procedure: Total lymphoid irradiation
    Total lymphoid irradiation (TLI) administered at 80cGy for 10 days
    Other Name: TLI
  • Drug: Rituximab
    Rituximab 375 mg/m2 administered as an intravenous (IV) infusion once weekly for 4 doses.
    Other Name: Rituxan
  • Drug: Anti-thymoglobulin, rabbit (ATG, rabbit ATG)
    Rabbit anti-thymoglobulin (ATG) administered from Day -11 through Day -7 (5 doses) at 1.5 mg/kg/day, for a total dose of 7.5 mg/kg.
  • Drug: Cyclosporine
    Cyclosporine (CSP) administered orally at 6.25 mg/kg twice-a-day (BID) from Day -3 until through Day +56 post-peripheral blood progenitor cell (PBPC) infusion. Dose may be adjusted to maintain a therapeutic level of cyclosporine, or in response to renal insufficiency. If at Day +56, chimerism assessment demonstrates > 40% donor cells in the CD3+ lineage, and the patient is without evidence of GvHD, then cyclosporine taper will begin (6% reduction per week).
    Other Names:
    • CSP
    • Sandimmune
  • Drug: Mycophenylate mofetil
    Mycophenylate mofetil (MMF) will be administered at 15 mg/kg po Day 0, at 5 to 10 hours after mobilized PBPC infusion is complete
    Other Names:
    • MMF
    • CellCept
  • Drug: Filgrastim
    Filgrastim provided as needed for neutrophil support
    Other Names:
    • G-CSF
    • Granulocyte-colony stimulating factor
    • Neupogen
  • Drug: Granisetron
    Granisetron administered as an anti-nausea agent (anti-emetic) at 1 mg orally 30 to 60 minutes before TLI
    Other Name: Sancuso
  • Drug: Solumedrol
    Solumedrol, an anti-inflammatory glucocorticoid containing methylprednisolone sodium succinate, administered at 1 mg/kg as a premedication for anti-thymoglobulin (ATG)
    Other Names:
    • Medrol
    • Depo-Medrol
    • A-Methapred
  • Drug: Acetaminophen
    Acetaminophen administered orally at 650 mg 1 hour prior to infusion of PBPC
    Other Name: Tylenol
  • Drug: Diphenhydramine
    Diphenhydramine administered by intravenous infusion at 50 mg 1 hour prior to infusion of PBPC
    Other Name: Benadryl
  • Drug: Hydrocortisone
    Hydrocortisone administered by intravenous infusion at 100 mg 1 hour prior to infusion of PBPC
    Other Name: Westcort
Experimental: Prophylactic Rituximab
Rituximab will be infused after a non-myeloablative transplantation regimen of total lymphoid irradiation (TLI) + anti-thymoglobulin (ATG), with the intention of reducing chronic graft-vs-host disease (cGvHD)
Interventions:
  • Procedure: Total lymphoid irradiation
  • Drug: Rituximab
  • Drug: Anti-thymoglobulin, rabbit (ATG, rabbit ATG)
  • Drug: Cyclosporine
  • Drug: Mycophenylate mofetil
  • Drug: Filgrastim
  • Drug: Granisetron
  • Drug: Solumedrol
  • Drug: Acetaminophen
  • Drug: Diphenhydramine
  • Drug: Hydrocortisone

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
36
35
December 2010
November 2010   (Final data collection date for primary outcome measure)

Recipient Inclusion Criteria:

  • Between 18 and 76 years of age
  • Chronic lymphocytic leukemia (CLL):

    • Unmutated IgG VH gene status
    • Mutated IgG VH genes (> 2% nucleotide change compared to somatic sequence)
    • Complete remission benefit most from allogeneic hematopoietic stem cell transplant (HSCT).

(Physicians will be encouraged to provide aggressive chemotherapy prior to nonmyeloablative transplantation.)

  • Mantle cell lymphoma (MCL): Transplant physicians believe subject would benefit from allogeneic HSCT.
  • Adequate renal (Cr < 2.4 mg/dL) and hepatic (Bilirubin < 3.0 mg/dL, Aspartate aminotransferase (AST) < 100 IU) function.
  • Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for six months after completion of treatment.
  • All subjects must provide written informed consent

Donor Inclusion Criteria:

  • Genotypically or phenotypically human leukocyte antigen (HLA)-identical.
  • Age < 76 unless cleared by institutional PI
  • Capable of giving written, informed consent.
  • Must consent to peripheral blood stem cell (PBSC) mobilization with G-CSF and apheresis

Recipient Exclusion Criteria:

  • Recipient has a 9 of 10 or 10 of 10 HLA identical donor (high resolution molecular genotyping at HLA A, B, C and DrB1, and DQ)
  • Pregnancy
  • Lactating
  • Serious uncontrolled infection
  • HIV seropositivity
  • Hepatitis B or C seropositivity
  • Cardiac function: ejection fraction < 40% or uncontrolled cardiac failure
  • Pulmonary: Diffusing capacity - carbon monoxide (DLCO) < 50% predicted
  • Liver function abnormalities: elevation of bilirubin to ≥ 3 mg/dL and/or AST > 100
  • Renal: creatinine > 2.4
  • Karnofsky performance score ≤ 60%
  • Patients with poorly controlled hypertension (systolic blood pressure > 150 or diastolic blood pressure > 90 repeatedly).
  • Known life-threatening hypersensitivity to rituximab or other anti-B cell antibodies.
  • Inability to comply with the allogeneic transplant treatment.
  • Uncontrolled central nervous system (CNS) involvement with disease

Donor Exclusion Criteria:

  • Identical twin to subject
  • Contra-indication to subcutaneous G-CSF at a dose of 16 mg/kg/d for 5 consecutive days
  • Serious medical or psychological illness
  • Prior malignancy within the preceding five years, with the exception of non-melanoma skin cancers.
  • HIV seropositivity
Sexes Eligible for Study: All
18 Years to 76 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00186628
IRB-02372
96160 ( Other Identifier: Stanford Secondary IRB Approval Number )
BMT172 ( Other Identifier: OnCore )
SPO ( Other Identifier: Leukemia & Lymphoma Society )
P01CA049605 ( U.S. NIH Grant/Contract )
Yes
Not Provided
Plan to Share IPD: No
David Miklos, Stanford University
Stanford University
  • The Leukemia and Lymphoma Society
  • National Cancer Institute (NCI)
Principal Investigator: David Miklos Stanford University
Stanford University
October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP