High-Dose Cyclophosphamide for Steroid Refractory GVHD

NCT00492921 | Completed Phase 2 Results

• 4 other identifiers: J06116P01CA015396P30CA006973NA_00003256
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Graft Versus Host Disease

Keywords

graft versus host disease

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose of High-dose Cyclophosphamide as Determined by Number of Participants Who Tolerated Each Dose of Cyclophosphamide

  Day 28

• 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

Study Arms (3)

Cyclophosphamide 50

EXPERIMENTAL

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

Drug: Cyclophosphamide

Cyclophosphamide 100

EXPERIMENTAL

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

Drug: Cyclophosphamide

Cyclophosphamide 150

EXPERIMENTAL

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

Drug: Cyclophosphamide

Interventions

Cyclophosphamide DRUG

Also known as: Cy, CTX, Cytoxan

Cyclophosphamide 100; Cyclophosphamide 150; Cyclophosphamide 50

Eligibility Criteria

• Age: Up to 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Dr. Javier Bolanos Meade
• Organization: JHU SKCCC

Fbolano2@jhmi.edu

410-614-6398

Study Officials

• Javier Bolanos-Meade, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2007
• First Posted: June 27, 2007
• Study Start: May 1, 2007
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: September 14, 2018
• Results First Posted: September 14, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)