Phase 2 Trial of Prophylactic Rituximab Therapy for Prevention of CGVHD

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00186628
Recruitment Status : Completed
First Posted : September 16, 2005
Results First Posted : November 28, 2017
Last Update Posted : November 28, 2017
The Leukemia and Lymphoma Society
National Cancer Institute (NCI)
Information provided by (Responsible Party):
David Miklos, Stanford University

Brief Summary:
To determine if rituximab administered after allogeneic transplantation decreases the incidence of chronic graft-vs-host disease (cGvHD)

Condition or disease Intervention/treatment Phase
Leukemia, Mast-Cell Mantle-cell Lymphoma 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 Phase 2

Detailed Description:
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).

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : June 2005
Actual Primary Completion Date : November 2010
Actual Study Completion Date : December 2010

Arm Intervention/treatment
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)
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

Primary Outcome Measures :
  1. 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)

Secondary Outcome Measures :
  1. Incidence of Relapse [ Time Frame: 4 years ]
    Subjects who Relapsed following after Allogeneic HSCT

  2. 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.

  3. Overall Survival [ Time Frame: 4 years ]

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Ages Eligible for Study:   18 Years to 76 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00186628

United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
The Leukemia and Lymphoma Society
National Cancer Institute (NCI)
Principal Investigator: David Miklos Stanford University

Publications of Results:
Other Publications:
Responsible Party: David Miklos, Assistant Professor of Medicine, Stanford University Identifier: NCT00186628     History of Changes
Obsolete Identifiers: NCT00234013
Other Study ID Numbers: 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 )
First Posted: September 16, 2005    Key Record Dates
Results First Posted: November 28, 2017
Last Update Posted: November 28, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Lymphoma, Mantle-Cell
Leukemia, Mast-Cell
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Mastocytosis, Systemic
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Methylprednisolone Hemisuccinate
Antilymphocyte Serum