Phase 2 Trial of Prophylactic Rituximab Therapy for Prevention of CGVHD

NCT00186628 | Completed Phase 2 Results DMC

• 5 other identifiers: IRB-0237296160BMT172SPOP01CA049605
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Leukemia, Mast-Cell; Mantle-cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Chronic Graft-vs-Host Disease (cGvHD)

  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 Outcomes (3)

• Incidence of Relapse

  4 years

• Mortality

  Day 100 and 1 year

• Overall Survival

  4 years

Study Arms (1)

Prophylactic Rituximab

EXPERIMENTAL

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; 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

Interventions

Total lymphoid irradiation PROCEDURE

Total lymphoid irradiation (TLI) administered at 80cGy for 10 days

Also known as: TLI

Prophylactic Rituximab

Rituximab DRUG

Rituximab 375 mg/m2 administered as an intravenous (IV) infusion once weekly for 4 doses.

Also known as: Rituxan

Prophylactic Rituximab

Anti-thymoglobulin, rabbit (ATG, rabbit ATG) DRUG

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.

Prophylactic Rituximab

Cyclosporine DRUG

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).

Also known as: CSP, Sandimmune

Prophylactic Rituximab

Mycophenylate mofetil DRUG

Mycophenylate mofetil (MMF) will be administered at 15 mg/kg po Day 0, at 5 to 10 hours after mobilized PBPC infusion is complete

Also known as: MMF, CellCept

Prophylactic Rituximab

Filgrastim DRUG

Filgrastim provided as needed for neutrophil support

Also known as: G-CSF, Granulocyte-colony stimulating factor, Neupogen

Prophylactic Rituximab

Granisetron DRUG

Granisetron administered as an anti-nausea agent (anti-emetic) at 1 mg orally 30 to 60 minutes before TLI

Also known as: Sancuso

Prophylactic Rituximab

Solumedrol DRUG

Solumedrol, an anti-inflammatory glucocorticoid containing methylprednisolone sodium succinate, administered at 1 mg/kg as a premedication for anti-thymoglobulin (ATG)

Also known as: Medrol, Depo-Medrol, A-Methapred

Prophylactic Rituximab

Acetaminophen DRUG

Acetaminophen administered orally at 650 mg 1 hour prior to infusion of PBPC

Also known as: Tylenol

Prophylactic Rituximab

Diphenhydramine DRUG

Diphenhydramine administered by intravenous infusion at 50 mg 1 hour prior to infusion of PBPC

Also known as: Benadryl

Prophylactic Rituximab

Hydrocortisone DRUG

Hydrocortisone administered by intravenous infusion at 100 mg 1 hour prior to infusion of PBPC

Also known as: Westcort

Prophylactic Rituximab

Eligibility Criteria

• Age: 18 Years - 76 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Stanford University: lead
• The Leukemia and Lymphoma Society: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Related Publications (2)

• Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005 Dec;11(12):945-56. doi: 10.1016/j.bbmt.2005.09.004.

  PMID: 16338616 BACKGROUND

• Arai S, Sahaf B, Narasimhan B, Chen GL, Jones CD, Lowsky R, Shizuru JA, Johnston LJ, Laport GG, Weng WK, Benjamin JE, Schaenman J, Brown J, Ramirez J, Zehnder JL, Negrin RS, Miklos DB. Prophylactic rituximab after allogeneic transplantation decreases B-cell alloimmunity with low chronic GVHD incidence. Blood. 2012 Jun 21;119(25):6145-54. doi: 10.1182/blood-2011-12-395970. Epub 2012 May 4.

  PMID: 22563089 RESULT

MeSH Terms

Conditions

Leukemia, Mast-Cell; Lymphoma, Mantle-Cell

Interventions

Rituximab; thymoglobulin; Cyclosporine; Mycophenolic Acid; Filgrastim; Granulocyte Colony-Stimulating Factor; Granisetron; Methylprednisolone Hemisuccinate; Methylprednisolone; Methylprednisolone Acetate; Acetaminophen; Diphenhydramine; Hydrocortisone; hydrocortisone valerate

Condition Hierarchy (Ancestors)

Leukemia; Neoplasms by Histologic Type; Neoplasms; Leukemia, Myeloid, Acute; Leukemia, Myeloid; Hematologic Diseases; Hemic and Lymphatic Diseases; Mastocytosis, Systemic; Mastocytosis; Mast Cell Activation Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Biological Factors; Azabicyclo Compounds; Aza Compounds; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Acetanilides; Anilides; Amides; Aniline Compounds; Amines; Ethylamines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Results Point of Contact

• Title: David Miklos, MD, PhD; Associate Professor of Medicine (Blood and Marrow Transplantation)
• Organization: Stanford University Medical Center

dmiklos@stanford.edu

650-725-4626

Study Officials

• David Miklos

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: September 14, 2005
• First Posted: September 16, 2005
• Study Start: June 1, 2005
• Primary Completion: November 1, 2010
• Study Completion: December 1, 2010
• Last Updated: November 28, 2017
• Results First Posted: November 28, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)