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CompletedNCT03007238Updated Apr 8, 2024Results posted

Extracorporeal Photopheresis and Low Dose Aldesleukin in Treating Patients With Steroid Refractory Chronic Graft-Versus-Host Disease

A Phase 2 interventional study of Aldesleukin and Extracorporeal Photopheresis in Chronic Graft Versus Host Disease, sponsored by City of Hope Medical Center. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-04-08.

Sponsored by City of Hope Medical Center · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
10
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

This phase II trial studies efficacy of extracorporeal photopheresis and low dose aldesleukin (interleukin-2) in treating patients with chronic graft-versus-host disease (cGVHD) that does not respond to upfront treatment with steroids. In graft-vs-host disease, patients have a small quantity of a white blood cell called T regulatory cells or T-reg cells that helps to control the immune system. Extracorporeal photopheresis is a procedure where patient's blood is removed and treated with ultraviolet light and drugs that become active when exposed to light. The treated blood is then returned to the patient and may be effective in increasing T-reg cells in patients with cGVHD. Aldesleukin increases the activity and growth of white blood cells, and it has shown to enhance T-reg cells in patients with cGVHD and may be effective improving GVHD symptoms.

Read the detailed description

PRIMARY OBJECTIVES:

I. To evaluate the anti-cGVHD activity of extracorporeal photopheresis (ECP) when combined with low dose IL-2 (interleukin 2) (aldesleukin), in patients with steroid refractory cGVHD, as assessed by overall cGVHD response rate (complete response [CR]+partial response [PR]+stable disease [SD]).

SECONDARY OBJECTIVES:

I. Characterize and evaluate toxicities, including type, frequency, severity, attribution, time course and duration.

II. Estimate overall and failure-free survival, non-relapse mortality (NRM) and relapse, through 1 year after initiation of treatment.

III. Characterize chronic GVHD Symptom Scale scores -self-report (with assistance from register nurses [RNs] and medical doctors [MDs]).

IV. Assess the immunologic effects of low-dose daily subcutaneous (SC) IL-2 + ECP.

V. Correlate clinical endpoints of response with ECP performance parameters.

OUTLINE:

Patients receive aldesleukin subcutaneously (SC) daily for 12 weeks. Patients also undergo ECP twice weekly on weeks 1-4 and then receive 2 ECP treatments every 2 weeks on weeks 5-12. Patients responding to upfront therapy with aldesleukin and ECP have the option to continue combination therapy per the discretion of the treating physician until clinical benefit is maintained or toxicities develop.

After completion of study treatment, patients are followed up periodically.

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Conditions studied

  • Chronic Graft Versus Host Disease
03

In context

Bronchiolitis Obliterans Syndrome

376 studies on the registry are indexed under Bronchiolitis Obliterans Syndrome; 104 are open to participants now.

This study's enrollment of 10 is below the median of 35 across 296 interventional studies indexed under Bronchiolitis Obliterans Syndrome.

Browse Bronchiolitis Obliterans Syndrome studies →

Lead sponsor

City of Hope Medical Center is the lead sponsor of 670 studies on the registry; 181 are open to participants now.

Of its 30 completed or terminated interventional studies of FDA-regulated products, 12 (40%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Recipients of allogeneic stem cell transplantation with myeloablative or non-myeloablative conditioning regimens; alternative donor transplants (umbilical cord blood and haploidentical) are allowed
  • Patients with chronic GVHD requiring systemic therapy are eligible
  • Participants must have steroid-refractory cGVHD, which is defined as having persistent signs and symptoms of cGVHD despite the use of prednisone at 0.20 mg/kg/day (or 0.5 mg/kg every other day) for at least 4 weeks (or equivalent dosing of alternate corticosteroids) without complete resolution of signs and symptoms
  • Karnofsky performance status of 70-100 %
  • Estimated life expectancy greater than 3 months
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
  • Stable dose of corticosteroids for 2 weeks prior to enrollment, i.e. the patient's steroid dose (mg/kg) will remain unchanged (eg 0.5 mg/kg) in the 2 weeks preceding enrollment; allowances will be made for up or down titrating the dose based on changes in body weight
  • Total bilirubin \< 2.0 mg/dl-exception permitted in patients with Gilbert's syndrome
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =\< 2 x upper limit of normal (ULN), unless hepatic dysfunction is a manifestation of presumed cGVHD
  • Abnormal liver function tests (LFTs) in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the LFTs as being consistent with hepatic cGVHD and a liver biopsy will not be mandated in this situation
  • Serum creatinine within normal institutional limits or creatinine clearance > 60 mL/min/1.73 m\^2 for participants with creatinine levels above institutional normal
  • Absolute neutrophil count (ANC) > 1000/mm\^3
  • Platelets > 50,000/mm\^3
  • All subjects must have the ability to understand and the willingness to sign a written informed consent
  • Patients with steroid refractory cGVHD typically have received salvage with multiple lines of therapy; hence in this trial there will be no restriction in terms of prior lines of therapy received; prior ECP exposure is allowed, however prior IL-2 use is excluded

Exclusion criteria

Exclusion Criteria:

  • Patients should not have any uncontrolled illness including ongoing or active infection; patients with an ongoing prednisone requirement of > 1 mg/kg/day (or equivalent) will be excluded
  • History of thrombotic microangiopathy, hemolytic-uremic syndrome or thrombotic thrombocytopenic purpura
  • Exposure to any new immunosuppressive medication in the 4 weeks prior to enrollment
  • Donor lymphocyte infusion within 100 days prior to enrollment
  • Active malignant relapse
  • Uncontrolled cardiac angina or symptomatic congestive heart failure (New York Heart Association [NYHA] class III or IV)
  • Human immunodeficiency virus (HIV)-positive individuals on combination antiretroviral therapy are ineligible
  • Patients may not be receiving any other investigational agents, or concurrent parenteral biological, chemotherapy, or radiation therapy. Oral chemotherapeutic agents or biologics-for example ruxolitinib therapy (either past or current exposure)-is allowed
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to IL-2
  • Patients must not have received prior chemotherapy (pentostatin) within 4 weeks before study enrollment, and those who have not recovered from the adverse events due to agents administered more than 4 weeks earlier are excluded
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with IL-2
  • Patients with other active malignancies are ineligible for this study, other than superficial localized skin cancer (basal or squamous cell carcinoma)
  • Subjects, who in the opinion of the investigator may not be able to comply with IL-2 or ECP treatment requirements or the safety monitoring requirements of the study, will be excluded from participation
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
10 participants (actual)

Study arms

  • Experimental
    Supportive care (aldesleukin and ECP)

    Patients receive aldesleukin SC daily for 12 weeks. Patients also undergo ECP twice weekly on weeks 1-4 and then receive 2 ECP treatments every 2 weeks on weeks 5-12. Patients responding to upfront therapy with aldesleukin and ECP have the option to continue combination therapy per the discretion of the treating physician until clinical benefit is maintained or toxicities develop.

    Biological: Aldesleukin · Procedure: Extracorporeal Photopheresis · Other: Laboratory Biomarker Analysis · Other: Quality-of-Life Assessment

Interventions

  • BiologicalAldesleukin

    Given SC

    Also known as: 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2, Recombinant Human Interleukin-2

  • ProcedureExtracorporeal Photopheresis

    Undergo ECP

    Also known as: Extracorporeal Photophoresis, photopheresis, Photophoresis

  • OtherLaboratory Biomarker Analysis

    Correlative studies

  • OtherQuality-of-Life Assessment

    Ancillary studies

    Also known as: Quality of Life Assessment

06

What researchers measure

Primary outcomes

  1. Overall Response Rate at Week 16 (4 Weeks After the End of Treatment)

    Defined as the proportion of response-evaluable participates that achieve a CR/PR or SD at Week 16 (4 weeks after the end of treatment).

    Time frame: At Week 16 (4 weeks after the end of treatment)

Secondary outcomes

  1. Failure-free Survival

    Failure-free survival will be estimated using the product-limit method of Kaplan and Meier.

    Time frame: From date of first dose of study drug to first documented cGVHD progression (necessitating change of treatment), malignancy relapse or progression or death from any cause, whichever occurs first, assessed up to 1 year

  2. Overall Survival

    Overall survival was estimated using the product-limit method of Kaplan and Meier.

    Time frame: From date of first dose of study drug to date of death from any cause, assessed up to 1 year

07

Results

Posted Apr 8, 2024

Participant flow

Participant flow — Overall Study
MilestoneOverall Study
Started10
Completed10
Not completed0

Outcome measures

PrimaryOverall Response Rate at Week 16 (4 Weeks After the End of Treatment)

Defined as the proportion of response-evaluable participates that achieve a CR/PR or SD at Week 16 (4 weeks after the end of treatment).

Time frame:
At Week 16 (4 weeks after the end of treatment)
Reported as:
Number · percentage of participants
Overall Response Rate at Week 16 (4 Weeks After the End of Treatment)
percentage of participantsTreatment (ECP+IL-2)
Overall response rate in patients who were alive at Week 16 (4 weeks after the end of treatment)88.9 (51.8 to 99.7)
Overall response rate by ITT80.0 (44.4 to 97.5)
SecondaryFailure-free Survival

Failure-free survival will be estimated using the product-limit method of Kaplan and Meier.

Time frame:
From date of first dose of study drug to first documented cGVHD progression (necessitating change of treatment), malignancy relapse or progression or death from any cause, whichever occurs first, assessed up to 1 year
Reported as:
Number · percentage of participants
Failure-free Survival
percentage of participantsOverall Study
Failure-free Survival40 (18.7 to 85.5)
SecondaryOverall Survival

Overall survival was estimated using the product-limit method of Kaplan and Meier.

Time frame:
From date of first dose of study drug to date of death from any cause, assessed up to 1 year
Reported as:
Number · percentage of participants
Overall Survival
percentage of participantsOverall Study
Overall Survival60 (36.2 to 99.5)

Adverse events

Collected over Adverse events were assessed from date of first dose of study drug up to 16 weeks. All-Cause Mortality was assessed from first dose until death, assessed up to 1 year.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Overall Study4/10 (40%)3/10 (30%)8/10 (80%)
Most frequent serious events
Most frequent serious events
EventOverall Study
SepsisInfections and infestations2/10
Atrial flutterCardiac disorders1/10
Bronchial infectionInfections and infestations1/10
Most frequent other events
Showing 10 of 23
Most frequent other events
EventOverall Study
AnemiaBlood and lymphatic system disorders3/10
HyperglycemiaMetabolism and nutrition disorders2/10
HypophosphatemiaMetabolism and nutrition disorders2/10
DyspneaRespiratory, thoracic and mediastinal disorders2/10
HypertensionVascular disorders2/10
Anal painGastrointestinal disorders1/10
NauseaGastrointestinal disorders1/10
Oral painGastrointestinal disorders1/10
Non-cardiac chest painGeneral disorders1/10
Catheter related infectionInfections and infestations1/10

Baseline characteristics

10 participants

Age, Continuous
Age, Continuous(years)Treatment (ECP Plus Low Dose IL-2)
Median46 (22 to 66)
Sex: Female, Male
Sex: Female, Male(Participants)Treatment (ECP Plus Low Dose IL-2)
Female6
Male4
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Treatment (ECP Plus Low Dose IL-2)
Hispanic or Latino3
Not Hispanic or Latino7
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Treatment (ECP Plus Low Dose IL-2)
American Indian or Alaska Native0
Asian1
Native Hawaiian or Other Pacific Islander0
Black or African American0
White8
More than one race0
Unknown or Not Reported1
Region of Enrollment
Region of Enrollment(participants)Treatment (ECP Plus Low Dose IL-2)
United States10
08

Study locations

1 site
  • City of Hope Medical Center
    Duarte, California 91010, United States
09

References and documents

Study documents

  • Protocol and statistical analysis plan · Apr 23, 2019

Documents are hosted by the registry — open the source record to download them.

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 8, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03007238
Lead sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Jan 2, 2017
Start date
Jan 18, 2017
Primary completion
Oct 16, 2018
Completion
Jun 26, 2019
Results posted
Apr 8, 2024
Last update
Apr 8, 2024

Study contacts

Amandeep Salhotra, MD
principal investigator · City of Hope Medical Center

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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