Trial record 11 of 202 for:    stem cell transplant | Open Studies | NIH, U.S. Fed

A Randomized, Controlled, Double-masked, Clinical Trial of Autologous Serum Eye Drops for Severe Ocular Chronic Graft-versus-host Disease (GVHD) in Hematopoietic Stem Cell Transplant (HSCT) Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Eye Institute (NEI) )
ClinicalTrials.gov Identifier:
NCT01972438
First received: October 23, 2013
Last updated: September 27, 2014
Last verified: June 2014
  Purpose

Objective: A common, serious and debilitating long term complication of hematopoietic stem cell transplant (HCST) is chronic graft-versus-host disease (GVHD). Ocular GVHD develops in up to 85% of patients with chronic GVHD. It is characterized by progressive keratitis sicca and cicatrizing ocular inflammatory surface disease with T cell mediated damage to conjunctival and corneal epithelium and lacrimal tissue. Various medical and surgical treatments have been used, such as various lubricating agents, steroid drops and ointments, cyclosporin drops, punctal plugs or cautery and partial tarsorrhaphy. However, in severe cases, none offer acceptable, long-lasting relief from pain, irritation, dryness and diminished vision associated with ocular GVHD. An alternative treatment that has previously been safely investigated is autologous serum eye drops (ASEDs). The objective of this study is to determine whether ASEDs are more effective than control (normal saline) in the treatment of severe chronic ocular GVHD in HSCT patients unresponsive to standard medical treatment.

Study Population: Thirty-four (34) post-HSCT patients with severe ocular GVHD unresponsive to standard medical treatment will be initially enrolled. Up to an additional 10 participants may be enrolled to account for participants who withdraw from the study prior to reaching Month 3.

Design: This is a Phase 2, randomized, double-masked, controlled, crossover, single-center study to investigate ASEDs in participants with severe chronic ocular GVHD. During the initial crossover phase of the study, participants will participate in a two-period, six-month, crossover study in which participants will be randomized to one of two treatment sequence groups. The two groups are: 1) daily administration of ASEDs for the first three months and then crossover to control (normal saline) eye drops beginning at Month 3 through Month 6, or 2) daily administration of control (normal saline) eye drops for the first three months and then crossover to ASEDs beginning at Month 3 through Month 6. Participants in both groups will apply the assigned drops four times per day in both eyes for six months, as well as maintain their current standard ocular GVHD therapy. Following the initial crossover phase, beginning at the Month 6 visit, participants will be provided ASEDs as open-label treatment on an as-needed basis until study completion. Participants and investigators will remain masked to the masked treatment sequence group assignments. During the first year, required clinic visits will occur at Baseline, Months 3, 6 and 12 with required telephone follow-up visits at Months 7 and 9. Following the Month 12 visit, participants will be evaluated every six months, alternating telephone follow-up visits with clinic visits, until the last enrolled participant reaches his/her Month 12 visit. At the baseline visit and as needed thereafter, all participants will supply blood for the preparation of the ASEDs.

Outcome Measures: The primary outcome is the proportion of participants experiencing a

greater than or equal to 50% reduction in the combined score of the modified Oxford punctate keratopathy grading and the NIH/NEI visual analogue scale in the study eye from baseline to Month 3. A greater than or equal to 50% reduction in the combined score will be considered a treatment success. While the design is a crossover study, the primary outcome is assessed after the first period at Month 3. Secondary outcomes include changes in the combined score of the modified Oxford punctate keratopathy grading and the NIH/NEI visual analogue scale in the study eye from baseline to the end of each period, changes in the chronic ocular GVHD Composite Assessment Scale (CAS) score, objective testing, subjective testing and global chronic GVHD assessments in both eyes. Safety outcomes will be the number and severity of systemic and ocular toxicities and adverse events. The number of participants withdrawn from the study treatment due to vision loss, adverse events or treatment failure will also contribute to the assessment of safety.


Condition Intervention Phase
Graft vs Host Disease
Drug: Autologous Serum Eye Drops
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Randomized, Controlled, Double-Masked, Clinical Trial of Autologous Serum Eye Drops for Severe Ocular Chronic Graft-versus-Host Disease (GVHD) in Hematopoietic Stem Cell Transplant (HSCT) Patients

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • The primary outcome is the proportion of participants experiencing a & gt; = 50% reduction in the combined score of the modified Oxford punctate keratopathy grading and the NIH/NEI visual analogue scale in the study eye from baseline to Mont... [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 44
Study Start Date: September 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Autologous Serum Eye Drops
    N/A
Detailed Description:

Objective: A common, serious and debilitating long term complication of hematopoietic stem cell transplant (HCST) is chronic graft-versus-host disease (GVHD). Ocular GVHD develops in up to 85% of patients with chronic GVHD. It is characterized by progressive keratitis sicca and cicatrizing ocular inflammatory surface disease with T cell mediated damage to conjunctival and corneal epithelium and lacrimal tissue. Various medical and surgical treatments have been used, such as various lubricating agents, steroid drops and ointments, cyclosporin drops, punctal plugs or cautery and partial tarsorrhaphy. However, in severe cases, none offer acceptable, long-lasting relief from pain, irritation, dryness and diminished vision associated with ocular GVHD. An alternative treatment that has previously been safely investigated is autologous serum eye drops (ASEDs). The objective of this study is to determine whether ASEDs are more effective than control (normal saline) in the treatment of severe chronic ocular GVHD in HSCT patients unresponsive to standard medical treatment.

Study Population: Thirty-four (34) post-HSCT patients with severe ocular GVHD unresponsive to standard medical treatment will be initially enrolled. Up to an additional 10 participants may be enrolled to account for participants who withdraw from the study prior to reaching Month 3.

Design: This is a Phase 2, randomized, double-masked, controlled, crossover, single-center study to investigate ASEDs in participants with severe chronic ocular GVHD. During the initial crossover phase of the study, participants will participate in a two-period, six-month, crossover study in which participants will be randomized to one of two treatment sequence groups. The two groups are: 1) daily administration of ASEDs for the first three months and then crossover to control (normal saline) eye drops beginning at Month 3 through Month 6, or 2) daily administration of control (normal saline) eye drops for the first three months and then crossover to ASEDs beginning at Month 3 through Month 6. Participants in both groups will apply the assigned drops four times per day for six months, as well as maintain their current standard ocular GVHD therapy. Following the initial crossover phase, beginning at the Month 6 visit, participants will be provided ASEDs as open-label treatment on an as-needed basis until study completion. Participants and investigators will remain masked to the masked treatment sequence group assignments. During the first year, required clinic visits will occur at Baseline, Months 3, 6 and 12 with required telephone follow-up visits at Months 7 and 9. Following the Month 12 visit, participants will be evaluated every six months, alternating telephone follow-up visits with clinic visits, until the last enrolled participant reaches his/her Month 12 visit. Within two weeks of the baseline visit and as needed thereafter, all participants will supply blood for the preparation of the ASEDs.

Outcome Measures: The primary outcome is the proportion of participants experiencing a

greater than or equal to 50% reduction in the combined score of the modified Oxford punctate keratopathy grading and the NIH/NEI visual analogue scale in the study eye from baseline to Month 3. A greater than or equal to 50% reduction in the combined score will be considered a treatment success. While the design is a crossover study, the primary outcome is assessed after the first period at Month 3. Secondary outcomes include changes in the combined score of the modified Oxford punctate keratopathy grading and the NIH/NEI visual analogue scale in both eyes from baseline to the end of each period, changes in the chronic ocular GVHD Composite Assessment Scale (CAS) score, objective testing, subjective testing and global chronic GVHD assessments in both eyes. Safety outcomes will be the number and severity of systemic and ocular toxicities and adverse events. The number of participants withdrawn from the study treatment due to vision loss, adverse events or treatment failure will also contribute to the assessment of safety.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

    1. Participant must be 18 years of age or older.
    2. Participant must understand and sign the protocol s informed consent document.
    3. Participant must have severe ocular GVHD in one (unilateral) or both (bilateral) eyes with the following characteristics in the study eye:

      1. Combined score of modified Oxford punctate keratopathy grading and NIH/NEI visual analogue scale of greater than or equal to 4, and
      2. Composite assessment scale score of greater than or equal 3, and
      3. Schirmer s tear test without anesthesia of less than or equal to 5 mm, and
      4. Not responsive to standard medical treatment for at least three months prior to randomization. Standard medical treatment includes cyclosporine (Restasis[R]) ophthalmic emulsion (if tolerated), steroid drops (unless contraindicated), lubricating drops and ointments.
    4. Participant is enrolled in an NIH study at the NCI or NHLBI.
    5. Participant is willing and able to supply an adequate amount of blood to create the ASEDs.

EXCLUSION CRITERIA:

  1. Participant is unable to comply with study procedures or follow-up visits.
  2. Participant is seropositive with positive nucleic acid confirmatory tests for HIV-12, HTLV-I/II, HCV, and/or HBV without confirmed history of vaccination.
  3. Participant has GVHD proliferative keratopathy, uveitis or GVHD retinopathy in either eye.
  4. Participant has an active ocular infection in either eye.
  5. Participant has an allergy to dilating or anesthetic eye drops.
  6. Participant has used Boston Scleral Lens (or similar lenses) in either eye or has used ASEDs in either eye within the past two months. Participants who have used the Boston Scleral Lens (or similar lenses) or ASEDs in either eye who did not respond to treatment and have stopped using them for at least two months are eligible.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01972438

Contacts
Contact: Angel H Garced, R.N. (301) 496-5847 garceda@mail.nih.gov
Contact: Manuel B Datiles, M.D. (301) 594-7052 datilesm@nei.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Manuel B Datiles, M.D. National Eye Institute (NEI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Eye Institute (NEI) )
ClinicalTrials.gov Identifier: NCT01972438     History of Changes
Other Study ID Numbers: 130206, 13-EI-0206
Study First Received: October 23, 2013
Last Updated: September 27, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Graft Versus Host Disease
Hematopoietic Stem Cell Transplant

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Ophthalmic Solutions
Tetrahydrozoline
Autonomic Agents
Cardiovascular Agents
Nasal Decongestants
Peripheral Nervous System Agents
Pharmaceutical Solutions
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Sympathomimetics
Therapeutic Uses
Vasoconstrictor Agents

ClinicalTrials.gov processed this record on October 20, 2014