High-Dose Cyclophosphamide for Steroid Refractory GVHD

Johns Hopkins Medicine

Status and phase: Completed; Phase 2

Conditions: Graft Versus Host Disease

Treatments: Drug: Cyclophosphamide

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00492921

NA_00003256 (Other Identifier)

P30CA006973 (U.S. NIH Grant/Contract)

P01CA015396 (U.S. NIH Grant/Contract)

J06116

Details and patient eligibility

About

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.

Full 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.

Enrollment: 12 patients

Sex: All

Ages: Under 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Supportive Care

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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12 participants in 3 patient groups

Cyclophosphamide 50

Experimental group

Description:

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

Treatment:

Drug: Cyclophosphamide

Cyclophosphamide 100

Experimental group

Description:

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

Treatment:

Drug: Cyclophosphamide

Cyclophosphamide 150

Experimental group

Description:

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

Treatment:

Drug: Cyclophosphamide