High-Dose Cyclophosphamide for Steroid Refractory GVHD

Graft Versus Host Disease Clinical Trial

Official title:

High-Dose Cyclophosphamide in Treating Patients With Acute Graft-Versus-Host Disease That Did Not Respond to Steroid Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00492921
• Other study ID #: J06116
• Secondary ID: P01CA015396P30CA
• Status: Completed
• Phase: Phase 2
• Start date: May 2007
• Est. completion date: January 2013

Study information

• Verified date: September 2018
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: High-dose cyclophosphamide may be an effective treatment for acute graft-versus-host disease that did not respond to steroid therapy.

PURPOSE: This phase II trial is studying the side effects, best dose, and how well high-dose cyclophosphamide works in treating patients with acute graft-versus-host disease that did not respond to steroid therapy.

Description:

OBJECTIVES:

• Determine the maximum tolerated dose of high-dose cyclophosphamide in patients with steroid refractory acute graft-versus-host disease (GVHD).

• Determine the efficacy of this regimen at 28 days post-treatment in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive high-dose cyclophosphamide once daily for 1-4 days beginning on day 1 and filgrastim (G-CSF) subcutaneously once daily beginning on day 10 and continuing until blood counts recover.

Cohorts of 3-6 patients receive escalating doses of high-dose cyclophosphamide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

After completion of study treatment, patients are followed weekly for 4 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 75 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed acute graft-versus-host disease (GVHD) = clinical grade II, that is steroid refractory

• Steroid refractory GVHD is defined as GVHD that has progressed (increasing in grading) despite 49 hours of treatment with methylprednisolone of = 2.0 mg/kg OR GVHD that has failed to improve (no change in grading stage) despite 4 days of treatment with methylprednisolone of = 2.0 mg/kg

• Prior allogeneic hematopoietic stem cell transplantation using either bone marrow, peripheral blood stem cells, or cord blood OR prior donor lymphocyte infusion required

• Evidence of myeloid engraftment

• No chronic GVHD

PATIENT CHARACTERISTICS:

• ECOG (Eastern Cooperative Oncology Group) performance status (PS) 0-2 OR Karnofsky PS 60-100%

• ANC (absolute neutrophil count) > 500/mm³

• Not pregnant or nursing

• Fertile patients must use effective contraception

• Must be geographically accessible

• No allergy or intolerance to cyclophosphamide or mesna

• No HIV positivity

• No mechanical ventilation

• No active bleeding (excluding gastrointestinal bleeding) or history of hemorrhagic cystitis

• No other uncontrolled illness including, but not limited to, the following:

• Ongoing or active infection

• Medical condition precluding patient from stopping azoles (e.g., fluconazole, itraconazole, or voriconazole) or other adequate antifungal therapy during cyclophosphamide administration

• Symptomatic congestive heart failure

• Unstable angina pectoris

• Psychiatric illness/social situations that would preclude compliance

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

Related Conditions & MeSH terms

• Graft Versus Host Disease
• Graft vs Host Disease

Intervention

Drug:
• Cyclophosphamide

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose of High-dose Cyclophosphamide as Determined by Number of Participants Who Tolerated Each Dose of Cyclophosphamide		Day 28
Primary	GVHD Response Rate	Percentage of patients whose GVHD (as defined by Przepiorka criteria) responded to cyclophosphamide (complete response). Acute GVHD is defined by the Przepiorka criteria, which stages the degree of organ involvement in the skin, liver, and gastrointestinal (GI) tract, based on severity, with Stage 1+ being least severe and stage 4+ being the most severe. Grading of acute GVHD is as follows: Grade I (skin involvement stages 1+ to 2+, with no liver or GI involvement), Grade II (skin involvement stages 1+ to 3+, liver 1+, GI tract 1+), Grade III (skin involvement stages 2+ to 3+, liver 1+, GI tract 2+ to 4+), Grade IV (skin involvement stages 4+, Liver 4+).	Day 28