Phase 2 Trial of Prophylactic Rituximab Therapy for Prevention of CGVHD

October 20, 2017 updated by: David Miklos, Stanford University

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)

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Enrollment (Actual)

36

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Stanford, California, United States, 94305
        • Stanford University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 76 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / 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 Names:
  • TLI
Drug: Rituximab
Rituximab 375 mg/m2 administered as an intravenous (IV) infusion once weekly for 4 doses.
Other Names:
  • 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:
  • Sandimmune
  • CSP
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:
  • CellCept
  • MMF
Drug: Filgrastim
Filgrastim provided as needed for neutrophil support
Other Names:
  • G-CSF
  • Neupogen
  • Granulocyte-colony stimulating factor
Drug: Granisetron
Granisetron administered as an anti-nausea agent (anti-emetic) at 1 mg orally 30 to 60 minutes before TLI
Other Names:
  • 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:
  • Depo-Medrol
  • Medrol
  • A-Methapred
Drug: Acetaminophen
Acetaminophen administered orally at 650 mg 1 hour prior to infusion of PBPC
Other Names:
  • Tylenol
Drug: Diphenhydramine
Diphenhydramine administered by intravenous infusion at 50 mg 1 hour prior to infusion of PBPC
Other Names:
  • Benadryl
Drug: Hydrocortisone
Hydrocortisone administered by intravenous infusion at 100 mg 1 hour prior to infusion of PBPC
Other Names:
  • Westcort

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
4 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: 4 years
4 years
Incidence of Relapse
Time Frame: 4 years
Subjects who Relapsed following after Allogeneic HSCT
4 years
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.
Day 100 and 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stanford University

Collaborators

National Cancer Institute (NCI)
The Leukemia and Lymphoma Society

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2005

Primary Completion (ACTUAL)

November 1, 2010

Study Completion (ACTUAL)

December 1, 2010

Study Registration Dates

First Submitted

September 14, 2005

First Submitted That Met QC Criteria

September 14, 2005

First Posted (ESTIMATE)

September 16, 2005

Study Record Updates

Last Update Posted (ACTUAL)

November 28, 2017

Last Update Submitted That Met QC Criteria

October 20, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB-02372
  • P01CA049605 (U.S. NIH Grant/Contract)
  • 96160 (OTHER: Stanford Secondary IRB Approval Number)
  • BMT172 (OTHER: OnCore)
  • SPO (OTHER: Leukemia & Lymphoma Society)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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