Discontinuation or Continuation of Immunosuppressive Therapy in Participants With Chronic Graft Versus Host Disease

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT03483675
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 21
• Location: 1
• Arms: 2
• Actual Duration (Months): 32.9
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This randomized trial studies how well discontinuation or continuation of immunosuppressive therapy works in treating participants with chronic graft versus host disease. Continuation of immunosuppressive treatment may prevent graft-versus-host disease worsening.

Condition or Disease	Intervention/Treatment	Phase
Chronic Graft Versus Host Disease	Biological: Immunosuppressive Therapy; Biological: Immunosuppressive Therapy; Other: Survey Administration	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

1. Assess feasibility of enrolling and randomizing patients with chronic graft versus host disease (GVHD) to discontinuation (standard of care) versus continuation (investigation) of immunosuppressive therapy (IST).

SECONDARY OBJECTIVES:

1. Assess feasibility of enrolling and randomizing patients who are not local, and evaluate the quality of data received for those patients.

2. Assess whether prolonged IST decreases the need for pulses of high dose IST.

3. Evaluate the effect of prolonged IST on chronic GVHD manifestations and severity, risk of relapse, infection and organ toxicity.

OUTLINE: Participants are randomized to 1 of 2 arms.

ARM I: Participants have their IST tapered and discontinued per the plan.

ARM II: Participants continue to receive a fixed dose IST for an additional 9 months with no taper.

After completion of study treatment, participants are followed up annually.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Feasibility Study of Discontinuation Versus Continuation of Immunosuppressive Therapy (IST) in Patients With Chronic Graft Versus Host Disease (GVHD)
• Actual Study Start Date: Jun 6, 2018
• Actual Primary Completion Date: May 14, 2020
• Actual Study Completion Date: Mar 3, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm I (discontinued IST) Participants have their IST tapered and discontinued per the plan.	Biological: Immunosuppressive Therapy; Discontinued IST; Other Names: Anti-Rejection Therapy immunosuppression ; Other: Survey Administration; Ancillary studies
Experimental: Arm II (continued IST) Participants continue to receive a fixed dose IST for an additional 9 months with no taper.	Biological: Immunosuppressive Therapy; Continued IST; Other Names: Anti-Rejection Therapy immunosuppression ; Other: Survey Administration; Ancillary studies

Outcome Measures

Primary Outcome Measures

1. Feasibility of Enrolling Patients [22.9 months]

   Descriptive summary of number of patients enrolled on the study (signed consent)

Secondary Outcome Measures

1. Feasibility of Randomizing Patients [22.9 months]

   Descriptive summary of percentage of patients randomized.

2. Compliance With Treatment [Up to 12 months after randomization]

   Rate of patients following study immunosuppressive therapy management based on study arm (standard taper or continuation of low dose).

3. Compliance With Data Collection [Up to 12 months after randomization]

   Count of surveys completed by physicians and patients

4. Graft Versus Host Disease Manifestations [Up to 12 months after randomization]

   New chronic graft versus host disease (GVHD) manifestations and/or worsening of existing manifestations

5. Recurrent Malignancy [Up to 12 months after randomization]

   Incidence of relapse of primary disease

6. Incidence of Grade >= 3 Infections [Up to 12 months after randomization]

   Incidence of grade >= 3 infections

7. Incidence of Grade >= 3 Organ Toxicity [Up to 12 months after randomization]

   Incidence of grade >= 3 organ toxicity

8. Enrollment Rate of Participants Who Are Not Local [Up to 12 months after randomization]

   Enrollment rate of participants who are not local. Participants who are local defined as those who had all or some study visits completed at the cancer center.

9. Quality of Data of Participants Who Are Not Local [Up to 12 months after randomization]

   Participants who are local defined as those who had all or some study visits completed at the cancer center.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Prior first allogeneic stem cell transplant, with any graft source, donor type, and GVHD prophylaxis

• Patients who are on one systemic immunosuppressive agent for chronic GVHD with a plan to withdraw all systemic IST; hydrocortisone or prednisone continued for treatment of adrenal insufficiency is not considered a systemic IST

• No evidence of malignancy at the time of enrollment

• Agree to be evaluated at the transplant center or by local provider every 3 months for 12 months after randomization

• Agreement to be contacted by phone or e-mail for health status evaluation for up to 3 years

• Signed, informed consent

Exclusion Criteria:

• Inability to comply with study procedures

• Pregancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Fred Hutchinson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Stephanie Lee, Fred Hutch/University of Washington Cancer Consortium

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 8, 2020
• Informed Consent Form - Oct 8, 2020

More Information

Publications

None provided.

• Responsible Party: Stephanie Lee, Professor and Associate Director, Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT03483675
• Other Study ID Numbers: 9962; NCI-2018-00323; 9962; P30CA015704; RG1001667
• First Posted: Mar 30, 2018
• Last Update Posted: Jun 23, 2021
• Last Verified: Jun 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Graft vs Host Disease; Immunosuppressive Agents

Study Results

Participant Flow

Pre-assignment Detail	4 participants were not randomized. 1 could not be reached and 3 had a GVHD flare after enrollment.

Arm/Group Title	Arm I (Discontinued IST)	Arm II (Continued IST)
Arm/Group Description	Participants have their IST tapered and discontinued per the plan.	Participants continue to receive a fixed dose IST for an additional 9 months with no taper.
Period Title: Overall Study
STARTED	9	8
COMPLETED	9	8
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Arm I (Discontinued IST)	Arm II (Continued IST)	Total
Arm/Group Description	Participants have their IST tapered and discontinued per the plan.	Participants continue to receive a fixed dose IST for an additional 9 months with no taper.	Total of all reporting groups
Overall Participants	9	8	17
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	4 44.4%	4 50%	8 47.1%
>=65 years	5 55.6%	4 50%	9 52.9%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	9 100%	8 100%	17 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	9 100%	8 100%	17 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 11.1%	1 12.5%	2 11.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 12.5%	1 5.9%
White	8 88.9%	5 62.5%	13 76.5%
More than one race	0 0%	1 12.5%	1 5.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	9 100%	8 100%	17 100%

Outcome Measures

1. Primary Outcome

Title	Feasibility of Enrolling Patients
Description	Descriptive summary of number of patients enrolled on the study (signed consent)
Time Frame	22.9 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Total Number of Participants
Arm/Group Description	Total number of participants who signed consent
Measure Participants	21
Count of Participants [Participants]	21 233.3%

2. Secondary Outcome

Title	Feasibility of Randomizing Patients
Description	Descriptive summary of percentage of patients randomized.
Time Frame	22.9 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Total Number of Participants
Arm/Group Description	Total number of participants who signed consent
Measure Participants	21
Count of Participants [Participants]	17 188.9%

3. Secondary Outcome

Title	Compliance With Treatment
Description	Rate of patients following study immunosuppressive therapy management based on study arm (standard taper or continuation of low dose).
Time Frame	Up to 12 months after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Discontinued IST)	Arm II (Continued IST)
Arm/Group Description	Participants have their IST tapered and discontinued per the plan.	Participants continue to receive a fixed dose IST for an additional 9 months with no taper.
Measure Participants	9	8
Count of Participants [Participants]	7 77.8%	8 100%

4. Secondary Outcome

Title	Compliance With Data Collection
Description	Count of surveys completed by physicians and patients
Time Frame	Up to 12 months after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Discontinued IST)	Arm II (Continued IST)
Arm/Group Description	Participants have their IST tapered and discontinued per the plan.	Participants continue to receive a fixed dose IST for an additional 9 months with no taper.
Measure Participants	9	8
Total surveys collected	48	39
Patient surveys missed	3	4
Physician surveys missed	5	6

5. Secondary Outcome

Title	Graft Versus Host Disease Manifestations
Description	New chronic graft versus host disease (GVHD) manifestations and/or worsening of existing manifestations
Time Frame	Up to 12 months after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Discontinued IST)	Arm II (Continued IST)
Arm/Group Description	Participants have their IST tapered and discontinued per the plan.	Participants continue to receive a fixed dose IST for an additional 9 months with no taper.
Measure Participants	9	8
Count of Participants [Participants]	2 22.2%	0 0%

6. Secondary Outcome

Title	Recurrent Malignancy
Description	Incidence of relapse of primary disease
Time Frame	Up to 12 months after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Discontinued IST)	Arm II (Continued IST)
Arm/Group Description	Participants have their IST tapered and discontinued per the plan.	Participants continue to receive a fixed dose IST for an additional 9 months with no taper.
Measure Participants	9	8
Count of Participants [Participants]	0 0%	0 0%

7. Secondary Outcome

Title	Incidence of Grade >= 3 Infections
Description	Incidence of grade >= 3 infections
Time Frame	Up to 12 months after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Discontinued IST)	Arm II (Continued IST)
Arm/Group Description	Participants have their IST tapered and discontinued per the plan.	Participants continue to receive a fixed dose IST for an additional 9 months with no taper.
Measure Participants	9	8
Count of Participants [Participants]	1 11.1%	0 0%

8. Secondary Outcome

Title	Incidence of Grade >= 3 Organ Toxicity
Description	Incidence of grade >= 3 organ toxicity
Time Frame	Up to 12 months after randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Discontinued IST)	Arm II (Continued IST)
Arm/Group Description	Participants have their IST tapered and discontinued per the plan.	Participants continue to receive a fixed dose IST for an additional 9 months with no taper.
Measure Participants	9	8
Count of Participants [Participants]	0 0%	0 0%

9. Secondary Outcome

Title	Enrollment Rate of Participants Who Are Not Local
Description	Enrollment rate of participants who are not local. Participants who are local defined as those who had all or some study visits completed at the cancer center.
Time Frame	Up to 12 months after randomization

Outcome Measure Data

Analysis Population Description

All participants were local, no data were collected for this outcome measure.

Arm/Group Title	Arm I (Discontinued IST)	Arm II (Continued IST)
Arm/Group Description	Participants have their IST tapered and discontinued per the plan.	Participants continue to receive a fixed dose IST for an additional 9 months with no taper.
Measure Participants	0	0

10. Secondary Outcome

Title	Quality of Data of Participants Who Are Not Local
Description	Participants who are local defined as those who had all or some study visits completed at the cancer center.
Time Frame	Up to 12 months after randomization

Outcome Measure Data

Analysis Population Description

All participants were local, no data were collected for this outcome measure.

Arm/Group Title	Arm I (Discontinued IST)	Arm II (Continued IST)
Arm/Group Description	Participants have their IST tapered and discontinued per the plan.	Participants continue to receive a fixed dose IST for an additional 9 months with no taper.
Measure Participants	0	0

Adverse Events

Time Frame	1 year
Arm/Group Title	Arm I (Discontinued IST)		Arm II (Continued IST)
Arm/Group Description	Participants have their IST tapered and discontinued per the plan. Immunosuppressive Therapy: Discontinued IST Survey Administration: Ancillary studies		Participants continue to receive a fixed dose IST for an additional 9 months with no taper. Immunosuppressive Therapy: Continued IST Survey Administration: Ancillary studies
All Cause Mortality
	Arm I (Discontinued IST)		Arm II (Continued IST)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/8 (0%)
Serious Adverse Events
	Arm I (Discontinued IST)		Arm II (Continued IST)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		2/8 (25%)
Cardiac disorders
heart failure	0/9 (0%)	0	1/8 (12.5%)	1
myocardial infarction	0/9 (0%)	0	1/8 (12.5%)	1
stent placement	0/9 (0%)	0	1/8 (12.5%)	1
Eye disorders
retinal detachment	0/9 (0%)	0	1/8 (12.5%)	1
Infections and infestations
Gangrene	0/9 (0%)	0	1/8 (12.5%)	1
osteomyelitis	0/9 (0%)	0	1/8 (12.5%)	1
wound complications	0/9 (0%)	0	1/8 (12.5%)	1
Vascular disorders
peripheral ischemia	0/9 (0%)	0	1/8 (12.5%)	1
Other (Not Including Serious) Adverse Events
	Arm I (Discontinued IST)		Arm II (Continued IST)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/9 (88.9%)		6/8 (75%)
Blood and lymphatic system disorders
iron deficiency anemia	0/9 (0%)	0	1/8 (12.5%)	1
thrombocytosis	1/9 (11.1%)	1	0/8 (0%)	0
Endocrine disorders
prostatitis, presumed	1/9 (11.1%)	1	0/8 (0%)	0
Eye disorders
corneal ulcer	1/9 (11.1%)	1	0/8 (0%)	0
floaters, eye	0/9 (0%)	0	1/8 (12.5%)	1
Gastrointestinal disorders
diarrhea	1/9 (11.1%)	1	1/8 (12.5%)	1
dysphagia	0/9 (0%)	0	1/8 (12.5%)	1
fecal incontinence	1/9 (11.1%)	1	0/8 (0%)	0
flatulence	0/9 (0%)	0	1/8 (12.5%)	1
gastroenteritis	1/9 (11.1%)	1	0/8 (0%)	0
GI upset, drug induced	0/9 (0%)	0	1/8 (12.5%)	2
hernia, umbilical	1/9 (11.1%)	1	0/8 (0%)	0
hypertriglyceridemia	1/9 (11.1%)	2	0/8 (0%)	0
nausea	3/9 (33.3%)	4	1/8 (12.5%)	1
constipation	0/9 (0%)	0	1/8 (12.5%)	1
General disorders
dizziness	1/9 (11.1%)	1	0/8 (0%)	0
fall	2/9 (22.2%)	2	0/8 (0%)	0
fatigue	2/2 (100%)	2	2/8 (25%)	2
fever	0/9 (0%)	0	1/8 (12.5%)	1
headache	1/9 (11.1%)	1	0/8 (0%)	0
insomnia	0/9 (0%)	0	2/8 (25%)	2
lightheadedness	1/9 (11.1%)	1	1/8 (12.5%)	1
weight gain or loss	1/9 (11.1%)	1	2/8 (25%)	2
Immune system disorders
leukopenia	2/9 (22.2%)	2	0/8 (0%)	0
Infections and infestations
Mucous cyst (toe)	1/9 (11.1%)	1	0/8 (0%)	0
thrush	0/9 (0%)	0	1/8 (12.5%)	1
Injury, poisoning and procedural complications
IV contrast reaction	1/9 (11.1%)	1	0/8 (0%)	0
Musculoskeletal and connective tissue disorders
arthralgia	2/9 (22.2%)	2	2/8 (25%)	2
fracture, clavicle	1/9 (11.1%)	1	0/8 (0%)	0
stiffness, muscular	2/9 (22.2%)	2	0/8 (0%)	0
myalgia	2/9 (22.2%)	2	3/8 (37.5%)	3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
squamous cell carcinoma	2/9 (22.2%)	2	2/8 (25%)	2
Nervous system disorders
essential tremor	0/9 (0%)	0	1/8 (12.5%)	1
neuropathy	1/9 (11.1%)	1	2/8 (25%)	2
seizure	1/9 (11.1%)	1	0/8 (0%)	0
Psychiatric disorders
depression	0/9 (0%)	0	1/8 (12.5%)	1
Renal and urinary disorders
acute kidney injury	0/9 (0%)	0	1/8 (12.5%)	1
elevated creatinine	1/9 (11.1%)	2	0/8 (0%)	0
urination, difficult	0/9 (0%)	0	1/8 (12.5%)	1
Reproductive system and breast disorders
phimosis	0/9 (0%)	0	1/8 (12.5%)	1
Respiratory, thoracic and mediastinal disorders
allergic rhinitis	0/9 (0%)	0	1/8 (12.5%)	1
dyspnea	1/9 (11.1%)	1	0/8 (0%)	0
cough	0/9 (0%)	0	1/8 (12.5%)	1
lower respiratory infection	4/9 (44.4%)	4	1/8 (12.5%)	1
upper respiratory infection	4/9 (44.4%)	8	4/8 (50%)	7
Skin and subcutaneous tissue disorders
anal fissures	0/9 (0%)	0	1/8 (12.5%)	1
eczema	1/9 (11.1%)	1	0/8 (0%)	0
skin, ulcer or lesion	1/9 (11.1%)	1	2/8 (25%)	2
skin, erythematous bumps, macules	0/9 (0%)	0	1/8 (12.5%)	2
skin, dermatitis, pruritis	1/9 (11.1%)	1	1/8 (12.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.