High-Dose Cyclophosphamide for Steroid Refractory GVHD

NCT ID: NCT00492921

Last Updated: 2018-09-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-31
• Study Completion Date: 2013-01-31

Brief 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.

Detailed 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.

Conditions

Graft Versus Host Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Cyclophosphamide 50

Treatment with cyclophosphamide 50 mg/kg/d x 1 days.

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

Cyclophosphamide 100

Treatment with cyclophosphamide 50 mg/kg/d x 2 days.

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

Cyclophosphamide 150

Treatment with cyclophosphamide 50 mg/kg/d x 3 days.

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

Interventions

Cyclophosphamide

Intervention Type: DRUG

Other Intervention Names

Cy; CTX; Cytoxan

Eligibility Criteria

Inclusion Criteria

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

• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Javier Bolanos-Meade, MD

Role: PRINCIPAL_INVESTIGATOR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

P01CA015396

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA006973

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NA_00003256

Identifier Type: OTHER

Identifier Source: secondary_id

J06116

Identifier Type: -

Identifier Source: org_study_id