Graft Versus Host DiseasePhase 2NCT00492921

High-Dose Cyclophosphamide for Steroid Refractory GVHD

A Phase 2 study testing Cyclophosphamide in people with Graft Versus Host Disease, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages Up to 75 years
Conditions the study is for: Graft Versus Host Disease
What is being tested?: Cyclophosphamide
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 12 participants
Where: 1 siteUnited States
Study dates: May 2007to Jan 2013
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Up to 75 years
All sexes
No healthy volunteers
Child, Adult, Older adult

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 locations and contacts

1 site in 1 country.

United States1 site

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

Other trials in United States

About this study

Official title: 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.

Read the 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
Being tested: Cyclophosphamide
Keywords: graft versus host disease
Medical subject headings: Graft vs Host Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CyclophosphamideDrug
Also called Cy, CTX, Cytoxan

Study groups in NCT00492921
Study group	Role	What they receive
Cyclophosphamide 50	Experimental	Treatment with cyclophosphamide 50 mg/kg/d x 1 days. Receives: Drug: Cyclophosphamide
Cyclophosphamide 100	Experimental	Treatment with cyclophosphamide 50 mg/kg/d x 2 days. Receives: Drug: Cyclophosphamide
Cyclophosphamide 150	Experimental	Treatment with cyclophosphamide 50 mg/kg/d x 3 days. Receives: Drug: Cyclophosphamide

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum Tolerated Dose of High-dose Cyclophosphamide as Determined by Number of Participants Who Tolerated Each Dose of Cyclophosphamide
Measured: 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+).
Measured: Day 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2007Jan 2013

First posted27 Jun 2007 (estimated)
Study startMay 2007
Primary completionJan 2013
Study completionJan 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Graft Versus Host DiseaseStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Supportive care
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 12 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00492921
Sponsor's protocol ID: J06116
Other IDs: P01CA015396, P30CA006973, NA_00003256
Status last verified: Sep 2018
First submitted: 25 Jun 2007
Last updated: 14 Sep 2018
Results posted: Yes, on ClinicalTrials.gov
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Graft Versus Host Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 14 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: High-Dose Cyclophosphamide in Treating Patients With Acute Graft-Versus-Host Disease That Did Not Respond to Steroid Therapy
ClinicalTrials.gov ID: NCT00492921
Acronym / sponsor ID: J06116
Conditions: Graft Versus Host Disease
Keywords: graft versus host disease
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 12 participants (actual)
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
Collaborators: National Cancer Institute (NCI)
Study start: May 2007
Primary completion: Jan 2013 (actual)
Study completion: Jan 2013 (actual)
First posted: 27 Jun 2007 (estimated)
Results: Posted 14 Sep 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

RATIONALE: High-dose cyclophosphamide may be an effective treatment for 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.

After completion of study treatment, patients are followed weekly for 4 weeks.

Study design

Primary purpose: Supportive care
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Cyclophosphamide 50	Experimental	Drug: CyclophosphamideTreatment with cyclophosphamide 50 mg/kg/d x 1 days.
Cyclophosphamide 100	Experimental	Drug: CyclophosphamideTreatment with cyclophosphamide 50 mg/kg/d x 2 days.
Cyclophosphamide 150	Experimental	Drug: CyclophosphamideTreatment with cyclophosphamide 50 mg/kg/d x 3 days.

Who may qualify

Ages: Up to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CyclophosphamideAlso: Cy, CTX, Cytoxan	Drug	Cyclophosphamide 100, Cyclophosphamide 150, Cyclophosphamide 50

Primary outcome

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

Results and safety

Results posted to the registry on 14 Sep 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cyclophosphamide 50 mg/kg	5	4
Cyclophosphamide 100 mg/kg	4	4
Cyclophosphamide 150 mg/kg	3	2

Primary outcome: Maximum Tolerated Dose of High-dose Cyclophosphamide as Determined by Number of Participants Who Tolerated Each Dose of Cyclophosphamide

Time frame: Day 28. Count of participants. Unit: Participants

Measure	Cyclophosphamide 50 mg/kg n = 5	Cyclophosphamide 100 mg/kg n = 4	Cyclophosphamide 150 mg/kg n = 3
Value	4	4	2

Primary outcome: GVHD Response Rate

Time frame: Day 28. Count of participants. Unit: Participants

Measure	Cyclophosphamide 50 mg/kg n = 4	Cyclophosphamide 100 mg/kg n = 4	Cyclophosphamide 150 mg/kg n = 2
Value	1	0	1

Population analysed: This analysis excludes the two participants who died early because their responses were not assessed prior to death.

Adverse events

Time frame: every week through Day 30. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cyclophosphamide 50 mg/kg	0 of 5 (0%)	0 of 5 (0%)	3 of 5
Cyclophosphamide 100 mg/kg	1 of 4 (25%)	0 of 4 (0%)	3 of 4
Cyclophosphamide 150 mg/kg	3 of 3 (100%)	0 of 3 (0%)	3 of 3

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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Active, not recruitingObservational study
Vaginal Microbiome and the Development of Vulvovaginal Graft Versus Host Disease
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RecruitingPhase 3
A Study to Evaluate Axatilimab and Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host Disease
Chronic Graft-versus-host-disease
Active, not recruiting
Patient Reported Outcomes With UVA-1 Therapy for Treatment of Sclerosing Skin Diseases
Scleroderma, Systemic, Morphea
Not yet recruiting
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Javier Bolanos-Meade, MD principal investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cyclophosphamide in people with Graft Versus Host Disease, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose of High-dose Cyclophosphamide as Determined by Number of Participants Who Tolerated Each Dose of Cyclophosphamide (time frame: Day 28). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00492921.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2018.