A Phase 2 Trial of Rituximab and Corticosteroid Therapy for Newly Diagnosed Chronic Graft Versus Host Disease

• ClinicalTrials.gov Identifier: NCT00350545
• Recruitment Status: Completed
• First Posted: July 10, 2006
• Results First Posted: November 20, 2017
• Last Update Posted: November 20, 2017
• Sponsor: Stanford University
• Information provided by (Responsible Party): Sally Arai, Stanford University

Study Description

Brief Summary:

The addition of rituximab to prednisone for the initial treatment of chronic GVHD will increase the overall response rate, enable a more rapid and effective steroid taper.

Condition or disease	Intervention/treatment	Phase
Graft vs Host Disease	Drug: Rituximab; Drug: Prednisone; Drug: Cyclosporine A; Drug: tacrolimus	Not Applicable

Detailed Description:

To determine the efficacy of Rituximab as first line of treatment of chronic GVHD. Efficacy will be defined as he ability to taper prednisone to a dose of 0.25 mg/kg per day by 6 months without clinical or GVHD relapse/ recurrence.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 37 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Trial of Rituximab and Corticosteroid Therapy for Newly Diagnosed Chronic Graft Versus Host Disease
• Study Start Date: August 2006
• Actual Primary Completion Date: May 2012
• Actual Study Completion Date: October 2014

Arms and Interventions

Arm

Intervention/treatment

Experimental: rituximab + prednisone arm; Rituximab will be given as an IV fusion as initial treatment, followed by predisone (given during registration) which will be continued through-out trial and tapered off by physician. Cyclosporine A and tacrolimus will be used if chances of new diagnosis of chronic GVHD occur. Both drugs have no interaction with Rituxan, but will be tapered off after predisone is completely tapered.

Drug: Rituximab; 375 mg/m2;IV infusion once weekly for four doses (days 1,8,15,22); option for second 4-week course at week 9; Other Name: Rituxan; Drug: Prednisone; 1 mg/kg; po per day with taper; Other Names: Deltasone; Liquid Pred; Meticorten; Orasone; Drug: Cyclosporine A; trough 200-300 or lower; po; Other Names: cyclosporine; Ciclosporin; Drug: tacrolimus; trough 5-10 or lower; po; Other Names: FK-506; Fujimycin

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With the Ability to Successfully Taper Prednisone to a Dose Lower Dose. [ Time Frame: 6 months ]
   Participants that have successfully tapered prednisone to a dose of 0.25 mg/kg/Day by 6 Months without clinical relapse.

Secondary Outcome Measures :

1. Number of Participants With Complete and/or Partial GVHD Response [ Time Frame: 6 months ]
   To have physician documentation of clinical GVHD response using organ staging and scoring scale- NIH clinical GVHD consensus response criteria applied 6 months after rituximab infusion began
2. Participants Who Reduced Steroid Use at One Year After Enrollment on the Trial [ Time Frame: 1 year ]
   Participants that decreased total daily corticosteroids ≤ 0.25mg/kg one year after rituximab infusion began
3. Failure-free Survival at 6 and 12 Months Post-Rituximab Initiation [ Time Frame: 6 and 12 Months ]
   Failure-free survival (FFS) was defined as participants who are surviving with no relapse and second line of cGVHD treatment.
4. Overall Survival [ Time Frame: 6 and 12 months ]
   Overall survival at 6 and 12 months

Eligibility Criteria

• Ages Eligible for Study: 1 Year to 75 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Children and adults with a new diagnosis of chronic GVHD- that requires systemic immunosuppressive treatment to a dose of 1mg/kg/day prednisone and who have undergone any type of donor hematopoietic cell graft or conditioning regimen.
• Stable doses of other immunosuppressive medications (e.g. calcineurin inhibitors, mycophenolate mofetil) for 2 weeks prior to enrollment. In addition, these other immunosuppressive medications should not be dose increased.
• 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.

Exclusion Criteria:

• Known life-threatening hypersensitivity to Rituximab or other anti-B cell antibody.
• Treatment with prednisone (or equivalent) at doses higher than 1 mg/kg/day at the time of enrollment. Persistent prednisone treatment of acute GVHD that is less than 1mg/kg is allowed.
• Active, uncontrolled infection- CMV reactivation is excluded (i.e. pneumonitis, colitis). Peripheral blood CMV reactivation is allowed as long as it is not associated with CMV disease and is responding to therapy.
• Known Hepatitis B surface Ag positive
• Active malignant disease relapse.
• Pregnancy
• Lactating
• Inability to comply with the Rituximab treatment regimen.

Contacts and Locations

Locations

United States, California

Stanford University School of Medicine

Stanford, California, United States, 94305

Sponsors and Collaborators

Stanford University

Investigators

• Principal Investigator: David Miklos; Stanford University
• Principal Investigator: Sally Arai; Stanford University

More Information

• Responsible Party: Sally Arai, Associate Professor of Medicine (Blood and Marrow Transplantation), Stanford University
• ClinicalTrials.gov Identifier: NCT00350545
• Other Study ID Numbers: IRB-04948; 96950 ( Other Identifier: Stanford University alternate IRB Number ); BMT177 ( Other Identifier: OnCore ); NCI-2011-00450 ( Other Identifier: National Cancer Institute (NCI) )
• First Posted: July 10, 2006
• Results First Posted: November 20, 2017
• Last Update Posted: November 20, 2017
• Last Verified: October 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: IPD will be available in the publication which is forthcoming.

Additional relevant MeSH terms:

Graft vs Host Disease; Immune System Diseases; Cyclosporine; Prednisone; Rituximab; Tacrolimus; Cyclosporins; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Immunosuppressive Agents; Calcineurin Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antifungal Agents; Anti-Infective Agents; Dermatologic Agents