High-Dose Cyclophosphamide for Steroid Refractory GVHD

September 11, 2018 updated by: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21231
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 75 years (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: SUPPORTIVE_CARE
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SEQUENTIAL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Cyclophosphamide 50
Treatment with cyclophosphamide 50 mg/kg/d x 1 days.
Drug: Cyclophosphamide
Other Names:
  • Cytoxan
  • CTX
  • Cy
EXPERIMENTAL: Cyclophosphamide 100
Treatment with cyclophosphamide 50 mg/kg/d x 2 days.
Drug: Cyclophosphamide
Other Names:
  • Cytoxan
  • CTX
  • Cy
EXPERIMENTAL: Cyclophosphamide 150
Treatment with cyclophosphamide 50 mg/kg/d x 3 days.
Drug: Cyclophosphamide
Other Names:
  • Cytoxan
  • CTX
  • Cy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose of High-dose Cyclophosphamide as Determined by Number of Participants Who Tolerated Each Dose of Cyclophosphamide
Time Frame: Day 28
Day 28
GVHD Response Rate
Time Frame: Day 28
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Javier Bolanos-Meade, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2007

Primary Completion (ACTUAL)

January 1, 2013

Study Completion (ACTUAL)

January 1, 2013

Study Registration Dates

First Submitted

June 25, 2007

First Submitted That Met QC Criteria

June 25, 2007

First Posted (ESTIMATE)

June 27, 2007

Study Record Updates

Last Update Posted (ACTUAL)

September 14, 2018

Last Update Submitted That Met QC Criteria

September 11, 2018

Last Verified

September 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • J06116
  • P30CA006973 (U.S. NIH Grant/Contract)
  • P01CA015396 (U.S. NIH Grant/Contract)
  • NA_00003256 (OTHER: JHMIRB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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