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High-Dose Cyclophosphamide for Steroid Refractory GVHD

Primary Purpose

Graft Versus Host Disease

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cyclophosphamide
Sponsored by
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Graft Versus Host Disease focused on measuring graft versus host disease

Eligibility Criteria

undefined - 75 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Cyclophosphamide 50

Cyclophosphamide 100

Cyclophosphamide 150

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose of High-dose Cyclophosphamide as Determined by Number of Participants Who Tolerated Each Dose of Cyclophosphamide
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+).

Secondary Outcome Measures

Full Information

First Posted
June 25, 2007
Last Updated
September 11, 2018
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00492921
Brief Title
High-Dose Cyclophosphamide for Steroid Refractory GVHD
Official Title
High-Dose Cyclophosphamide in Treating Patients With Acute Graft-Versus-Host Disease That Did Not Respond to Steroid Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
May 2007 (undefined)
Primary Completion Date
January 2013 (Actual)
Study Completion Date
January 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft Versus Host Disease
Keywords
graft versus host disease

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cyclophosphamide 50
Arm Type
Experimental
Arm Description
Treatment with cyclophosphamide 50 mg/kg/d x 1 days.
Arm Title
Cyclophosphamide 100
Arm Type
Experimental
Arm Description
Treatment with cyclophosphamide 50 mg/kg/d x 2 days.
Arm Title
Cyclophosphamide 150
Arm Type
Experimental
Arm Description
Treatment with cyclophosphamide 50 mg/kg/d x 3 days.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cy, CTX, Cytoxan
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose of High-dose Cyclophosphamide as Determined by Number of Participants Who Tolerated Each Dose of Cyclophosphamide
Time Frame
Day 28
Title
GVHD Response Rate
Description
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+).
Time Frame
Day 28

10. Eligibility

Sex
All
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Javier Bolanos-Meade, MD
Organizational Affiliation
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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High-Dose Cyclophosphamide for Steroid Refractory GVHD

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