Graft Versus Host DiseasePhase 3NCT00361413
Alefacept for Prevention of Graft Versus Host Disease (GVHD)
A Phase 3 study testing Alefacept (AMEVIVE®) in people with Graft Versus Host Disease, run by Hadassah Medical Organization at 1 site in Israel.
Trial summary
Alefacept (AMEVIVE®) is an immunosuppressive dimeric fusion protein. It was shown to interfere with lymphocyte activation by specifically binding to the lymphocyte antigen, CD2, and inhibiting LFA-3/CD2 interaction. Read more about this study
- Who is it for?
- Ages 14 to 75 years
- Conditions the study is for
- Graft Versus Host Disease
- What is being tested?
- Alefacept (AMEVIVE®)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 1 siteIsrael
- Study dates
- Jun 2006to Dec 2013
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 14 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patient age 14-75 years old with a disease necessitating allogeneic SCT.
- In order to increase security, only full matched donors will be allowed and must be willing and capable of donating peripheral blood stem cells preferably, or bone marrow progenitor cells using conventional techniques, and lymphocytes if indicated.
- Patients must sign written informed consents.
- Patients must have an ECOG PS ≤ 2; creatinine < 2.0 mg/dl; ejection fraction > 40%; DLCO > 50% of predicted; serum bilirubin < 3 gm/dl; elevated GPT or GOT > 3 x normal values.
Who cannot join
- Not fulfilling any of the inclusion criteria.
- Active life-threatening infection.
- Overt untreated infection.
- Hypersensitivity to alefacept.
- HIV seropositivity, Hepatitis B or C antigen positivity with active hepatitis.
- Pregnant or lactating women.
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- Donor contraindication (HIV seropositive confirmed by western blot).
- Hepatitis B antigenemia.
- Evidence of bone marrow disease.
- Unable to donate bone marrow or peripheral blood due to concurrent medical condition.
- Inability to comply with study requirements.
Trial locations and contacts
1 site in 1 country.
Israel1 site
Department of Stem Cell Transplantation & Cancer Immunotherapy
Jerusalem, 91120
About this study
Official title: An Investigator Initiated Double Blind Randomized Study of Alefacept Treatment Prevention of Graft Versus Host Disease in Myeloablative Stem Cell Transplantation
Alefacept (AMEVIVE®) is an immunosuppressive dimeric fusion protein. It was shown to interfere with lymphocyte activation by specifically binding to the lymphocyte antigen, CD2, and inhibiting LFA-3/CD2 interaction. Alefacept was evaluated in two randomized, double-blind, placebo-controlled studies in adults with chronic (>1 year) plaque psoriasis and a minimum body surface area involvement of 10% who were candidates for or had previously received systemic therapy or phototherapy. The response to alefacept was significantly better in both studies. In both studies, onset of response to alefacept treatment (defined as at least 50% reduction of baseline Psoriasis Area and Severity Index (PASI)) began 60 days after the start of therapy.
Graft versus host disease (GVHD) is the most ominous side effect of allogeneic stem cell transplantation (SCT). It causes severe inflammatory process, which is usually located to the skin, gut and liver. Treatment of GVHD consists of various immuno-suppressive and immuno-modulating drugs, including steroids, cyclosporine, tacrolimus, methotrexate etc. These drugs unfortunately can also cause severe immunologic failure that makes the patient prone to infection and malignancy, and other medication-specific side effects. In spite of this effect on the immune system, not all of the patients achieve control of GVHD, which usually rapidly leads to death. Despite the use of innovative immunosuppressive modalities, the prognosis of steroid resistant GVHD is usually poor.
It was shown that CD2 depletion of allografts could prevent GVHD. Alefacept was never systemically tried in GVHD but A phase II study of BTI-322, a rat monoclonal IgG2b directed against the CD2 antigen in steroid-refractory acute GVHD showed a total response rate of 55%. We showed that alefacept might have a beneficial effect in controlling steroid resistant aGVHD and chronic GVHD. It was also shown to dramatically change the nature of transfusion associated GVHD.
- Conditions
- Graft Versus Host Disease
- Being tested
- Alefacept (AMEVIVE®), control group
- Keywords
- Stem cell transplantation, GVHD, 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.
Alefacept (AMEVIVE®)Drug
Also called Alefacept
Alefacept
control groupDrug
these patients will receive the same treatment as group A, without alefacept
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Alefacept Receives: Drug: Alefacept (AMEVIVE®) |
| 2 | Placebo comparator | Not described Receives: Drug: control group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acute GVHD occurrence.
Measured: 100d
Acute GVHD grading.
Measured: 100d
Secondary outcomes (10)
Time to acute GVHD.
Measured: 100d
Chronic GVHD occurrence.
Measured: 180d
Chronic GVHD grading.
Measured: 180d
Engraftment/graft rejection.
Measured: 21d
Overall survival.
Measured: 180d
Disease free survival.
Measured: 180d
Infections.
Measured: 180d
Transplant-related mortality (TRM).
Measured: 180d
Immune reconstitution
Measured: 180d
Toxicity assessment according to the Common Terminology Criteria for Adverse Events (CTCAE)
Measured: 180d
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2006 (estimated)
- Study startJun 2006
- Primary completionJul 2013
- Study completionDec 2013
Why it stopped: company withdrawal of the drug
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Graft Versus Host DiseaseStudies of the same condition, open and under way.
- More trials run by Hadassah Medical OrganizationThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hadassah Medical Organization
- Sponsor type
- University, hospital or other
- Investigators
- Michael Y Shapira, MD, Principal investigator, Hadassah Medical Organization
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00361413
- Sponsor's protocol ID
- MYS-01-HMO-CTIL
- Status last verified
- Dec 2010
- First submitted
- 31 Jul 2006
- Last updated
- 21 Apr 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Shapira MY, Resnick IB, Bitan M, Ackerstein A, Tsirigotis P, Gesundheit B, Zilberman I, Miron S, Leubovic A, Slavin S, Or R. Rapid response to alefacept given to patients with steroid resistant or steroid dependent acute graft-versus-host disease: a preliminary report. Bone Marrow Transplant. 2005 Dec;36(12):1097-101. doi: 10.1038/sj.bmt.1705185.
PubMed 16247429
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Investigator Initiated Double Blind Randomized Study of Alefacept Treatment Prevention of Graft Versus Host Disease in Myeloablative Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT00361413
- Acronym / sponsor ID
- MYS-01-HMO-CTIL
- Conditions
- Graft Versus Host Disease
- Keywords
- Stem cell transplantation, GVHD, Graft Versus Host Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: company withdrawal of the drug
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Hadassah Medical OrganizationUniversity, hospital or other
- Study start
- Jun 2006
- Primary completion
- Jul 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 8 Aug 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Alefacept (AMEVIVE®) is an immunosuppressive dimeric fusion protein. It was shown to interfere with lymphocyte activation by specifically binding to the lymphocyte antigen, CD2, and inhibiting LFA-3/CD2 interaction. Alefacept was evaluated in two randomized, double-blind, placebo-controlled studies in adults with chronic (>1 year) plaque psoriasis and a minimum body surface area involvement of 10% who were candidates for or had previously received systemic therapy or phototherapy. The response to alefacept was significantly better in both studies. In both studies, onset of response to alefacept treatment (defined as at least 50% reduction of baseline Psoriasis Area and Severity Index (PASI)) began 60 days after the start of therapy.
Graft versus host disease (GVHD) is the most ominous side effect of allogeneic stem cell transplantation (SCT). It causes severe inflammatory process, which is usually located to the skin, gut and liver. Treatment of GVHD consists of various immuno-suppressive and immuno-modulating drugs, including steroids, cyclosporine, tacrolimus, methotrexate etc. These drugs unfortunately can also cause severe immunologic failure that makes the patient prone to infection and malignancy, and other medication-specific side effects. In spite of this effect on the immune system, not all of the patients achieve control of GVHD, which usually rapidly leads to death. Despite the use of innovative immunosuppressive modalities, the prognosis of steroid resistant GVHD is usually poor.
It was shown that CD2 depletion of allografts could prevent GVHD. Alefacept was never systemically tried in GVHD but A phase II study of BTI-322, a rat monoclonal IgG2b directed against the CD2 antigen in steroid-refractory acute GVHD showed a total response rate of 55%. We showed that alefacept might have a beneficial effect in controlling steroid resistant aGVHD and chronic GVHD. It was also shown to dramatically change the nature of transfusion associated GVHD.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Alefacept (AMEVIVE®)Alefacept |
| 2 | Placebo comparator | Drug: control group |
Who may qualify
- Ages
- 14 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Patient age 14-75 years old with a disease necessitating allogeneic SCT.
- In order to increase security, only full matched donors will be allowed and must be willing and capable of donating peripheral blood stem cells preferably, or bone marrow progenitor cells using conventional techniques, and lymphocytes if indicated.
- Patients must sign written informed consents.
- Patients must have an ECOG PS ≤ 2; creatinine < 2.0 mg/dl; ejection fraction > 40%; DLCO > 50% of predicted; serum bilirubin < 3 gm/dl; elevated GPT or GOT > 3 x normal values.
Key exclusion criteria (11 listed)
- Not fulfilling any of the inclusion criteria.
- Active life-threatening infection.
- Overt untreated infection.
- Hypersensitivity to alefacept.
- HIV seropositivity, Hepatitis B or C antigen positivity with active hepatitis.
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 |
|---|---|---|
| Alefacept (AMEVIVE®)Also: AlefaceptAlefacept | Drug | 1 |
| control groupthese patients will receive the same treatment as group A, without alefacept | Drug | 2 |
Primary outcome
Acute GVHD occurrence.
Time frame: 100d
Acute GVHD grading.
Time frame: 100d
10 secondary outcomes
Time to acute GVHD.
Time frame: 100d
Chronic GVHD occurrence.
Time frame: 180d
Chronic GVHD grading.
Time frame: 180d
Engraftment/graft rejection.
Time frame: 21d
Overall survival.
Time frame: 180d
Disease free survival.
Time frame: 180d
Infections.
Time frame: 180d
Transplant-related mortality (TRM).
Time frame: 180d
Immune reconstitution
Time frame: 180d
Toxicity assessment according to the Common Terminology Criteria for Adverse Events (CTCAE)
Time frame: 180d
Results and safety
The study was stopped early (reason given: company withdrawal of the drug). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2015.
- Background: PubMed 16247429Shapira MY, Resnick IB, Bitan M, Ackerstein A, Tsirigotis P, Gesundheit B, Zilberman I, Miron S, Leubovic A, Slavin S, Or R. Rapid response to alefacept given to patients with steroid resistant or steroid dependent acute graft-versus-host disease: a preliminary report. Bone Marrow Transplant. 2005 Dec;36(12):1097-101. doi: 10.1038/sj.bmt.1705185.
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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.
Michael Y Shapira, MD principal investigator
Hadassah Medical Organization
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Alefacept (AMEVIVE®) in people with Graft Versus Host Disease, run by Hadassah Medical Organization at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. 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: stopped early, as of the sponsor's last update on 21 Apr 2015. 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 Israel. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: company withdrawal of the drug). Results are not available in the source record.
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?
Acute GVHD occurrence. (time frame: 100d). 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 NCT00361413, which also lists 1 linked publication.
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 21 Apr 2015.