Myelodysplastic SyndromePhase 2NCT00466843
Effects of Antithymocyte Globulin in Adults With Myelodysplastic Syndrome
A Phase 2 study testing Antithymocyte globulin (ATG) and Prednisone in people with Myelodysplastic Syndrome, run by Office of Rare Diseases (ORD) at 4 sites in United States.
Trial summary
Myelodysplastic syndrome (MDS) is a rare, potentially serious bone marrow disease. Currently available treatments for MDS have been only somewhat beneficial. The purpose of this study is to determine the effects of the medication antithymocyte globulin (ATG) in adults with MDS and to determine which individuals with… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndrome
- What is being tested?
- Antithymocyte globulin (ATG) and Prednisone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 4 sitesUnited States
- Study dates
- Apr 2007to Feb 2010
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of MDS that meets International Prognostic Scoring System (IPSS) criteria for low risk, intermediate-1 risk, or intermediate-2 risk. More information about this criterion can be found in the protocol.
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
- Willing and able to attend study visits
- Willing to use acceptable forms of contraception prior to study entry and for the duration of the study
Who cannot join
- Any serious medical illness that might limit survival to less than 2 years
- Any other uncontrolled condition or illness. More information about this criterion can be found in the protocol.
- Prior anti-lymphocyte serotherapy (received serum from an immunized animal)
- Proliferative chronic myelomonocytic leukemia
- MDS that is caused by radiotherapy, chemotherapy, and/or immunotherapy for cancerous or autoimmune diseases
- Previous or current cancer. More information about this criterion can be found in the protocol.
Show all 12Show fewer
- Receiving any other investigational agents
- Certain abnormal lab values. More information about this criterion can be found in the protocol.
- History of a grade 2 National Cancer Institute common toxic criteria allergic reaction to rabbit proteins
- Psychiatric illness that might interfere with study participation
- HIV-1 infection
- Pregnancy or breastfeeding
Trial locations and contacts
4 sites in 1 country.
United States4 sites, 4 recruiting
- Recruiting
Cleveland Clinic Foundation - Case Western University
Cleveland, Ohio, 44195
Robin Heggeland, RN, heggelr@ccf.org
Jaroslaw P. Maciejewski, MD, PhD
- Recruiting
Penn State University
Hershey, Pennsylvania, 17033
Lynn Ruiz, lruiz@psu.edu
Thomas P. Loughran, Jr., MD
- Not yet recruiting
UCLA Oncology Center
Los Angeles, California, 90095
Troy Overfield, toverfield@mednet.ucla.edu
Ronald Paquette, MD
- Recruiting
H. Lee Moffitt Cancer Center
Tampa, Florida, 33612
Tera Uliano, RN, 813-745-1706
Alan List, MD
About this study
Official title: Mechanism and Response of Thymoglobulin in Patients With Myelodysplastic Syndrome (MDS)
Myelodysplastic syndrome (MDS) is a rare, potentially serious bone marrow disease. Currently available treatments for MDS have been only somewhat beneficial. The purpose of this study is to determine the effects of the medication antithymocyte globulin (ATG) in adults with MDS and to determine which individuals with MDS are most likely to benefit from treatment with ATG.
Read the detailed description
In people with MDS, the bone marrow stops making healthy blood cells and instead produces poorly functioning, malformed, and immature blood cells. This can lead to anemia resulting from too few healthy red blood cells, infection resulting from too few healthy white blood cells, and bleeding resulting from too few healthy platelets. The exact cause of MDS remains unknown, but it may be caused by abnormal autoimmune activity in which activated T cells, a type of white blood cell, prevent normal bone marrow production. ATG, a medication that inhibits immune function, can restore normal blood production in some people with MDS, but it is not known how this happens and why it does not happen in all MDS patients. The purpose of this study is to examine the effects of ATG in adults with MDS and to determine which individuals with MDS are most likely to benefit from treatment with ATG.
Based on disease severity and likely disease progression, participants will be separated into either a high-risk group or a low-risk group. Participants will be hospitalized for a 4-day period during which they will receive daily infusions of ATG. Oral prednisone will be given 2 days before hospitalization, throughout hospitalization, and then for 14 days after hospitalization to limit the side effects of ATG. Antihistamines and acetaminophen will also be given during hospitalization to reduce the chances of an allergic reaction to ATG. After discharge, all participants will attend monthly study visits that will include blood collection, review of disease symptoms, and evaluation of medication response. At Week 16, participants in the high-risk group will undergo additional blood collection, a bone marrow biopsy, and a thorough evaluation of disease progression and the effects of MDS on daily living abilities. Participants in the low-risk group will undergo these same procedures at Week 24. Follow-up for all participants may last up to 2 years.
- Conditions
- Myelodysplastic Syndrome
- Being tested
- Antithymocyte globulin (ATG), Prednisone
- Keywords
- Abnormal hematopoiesis, Leukemia, Autoimmune Disease
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Autoimmune Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Antithymocyte globulin (ATG)Drug
ATG 2.5 mg/kg/day via IV will be given for 4 doses. Each participant will receive only one cycle of therapy. The daily infusion will be administered over at least 6 hours and slowed as necessary to minimize infusion-related symptoms.
PrednisoneDrug
All participants will be pre-treated with prednisone (1 mg/kg/day by mouth) 2 days prior to the first ATG does and continuing for 14 days after the final dose to prevent serum sickness
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Participants will be treated with ATG Receives: Drug: Antithymocyte globulin (ATG); Drug: Prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bone marrow response and hematologic improvement
Measured: Measured at Week 16 or 24
Bone marrow cytogenetic response
Measured: Measured at Week 16 or 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2007 (estimated)
- Study startApr 2007
- Primary completionFeb 2010 (estimated)
- Study completionFeb 2010 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Myelodysplastic SyndromeStudies 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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Office of Rare Diseases (ORD)
- Sponsor type
- US National Institutes of Health
- Collaborators
- Rare Diseases Clinical Research Network
- Investigators
- Alan List, MD, Principal investigator, H. Lee Moffitt Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00466843
- Sponsor's protocol ID
- RDCRN 5406
- Status last verified
- Jun 2009
- First submitted
- 25 Apr 2007
- Last updated
- 2 Jun 2009
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Kochenderfer JN, Kobayashi S, Wieder ED, Su C, Molldrem JJ. Loss of T-lymphocyte clonal dominance in patients with myelodysplastic syndrome responsive to immunosuppression. Blood. 2002 Nov 15;100(10):3639-45. doi: 10.1182/blood-2002-01-0155. Epub 2002 Jul 5.
PubMed 12393644Maciejewski JP, Rivera C, Kook H, Dunn D, Young NS. Relationship between bone marrow failure syndromes and the presence of glycophosphatidyl inositol-anchored protein-deficient clones. Br J Haematol. 2001 Dec;115(4):1015-22. doi: 10.1046/j.1365-2141.2001.03191.x.
PubMed 11843844Molldrem JJ, Leifer E, Bahceci E, Saunthararajah Y, Rivera M, Dunbar C, Liu J, Nakamura R, Young NS, Barrett AJ. Antithymocyte globulin for treatment of the bone marrow failure associated with myelodysplastic syndromes. Ann Intern Med. 2002 Aug 6;137(3):156-63. doi: 10.7326/0003-4819-137-3-200208060-00007.
PubMed 12160363Komrokji RS, Mailloux AW, Chen DT, Sekeres MA, Paquette R, Fulp WJ, Sugimori C, Paleveda-Pena J, Maciejewski JP, List AF, Epling-Burnette PK. A phase II multicenter rabbit anti-thymocyte globulin trial in patients with myelodysplastic syndromes identifying a novel model for response prediction. Haematologica. 2014 Jul;99(7):1176-83. doi: 10.3324/haematol.2012.083345. Epub 2014 Jan 31.
PubMed 24488560
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanism and Response of Thymoglobulin in Patients With Myelodysplastic Syndrome (MDS)
- ClinicalTrials.gov ID
- NCT00466843
- Acronym / sponsor ID
- RDCRN 5406
- Conditions
- Myelodysplastic Syndrome
- Keywords
- Abnormal hematopoiesis, Leukemia, Autoimmune Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- Office of Rare Diseases (ORD)US National Institutes of Health
- Collaborators
- Rare Diseases Clinical Research Network
- Study start
- Apr 2007
- Primary completion
- Feb 2010 (estimated)
- Study completion
- Feb 2010 (estimated)
- First posted
- 27 Apr 2007 (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.
Myelodysplastic syndrome (MDS) is a rare, potentially serious bone marrow disease. Currently available treatments for MDS have been only somewhat beneficial. The purpose of this study is to determine the effects of the medication antithymocyte globulin (ATG) in adults with MDS and to determine which individuals with MDS are most likely to benefit from treatment with ATG.
Detailed description
In people with MDS, the bone marrow stops making healthy blood cells and instead produces poorly functioning, malformed, and immature blood cells. This can lead to anemia resulting from too few healthy red blood cells, infection resulting from too few healthy white blood cells, and bleeding resulting from too few healthy platelets. The exact cause of MDS remains unknown, but it may be caused by abnormal autoimmune activity in which activated T cells, a type of white blood cell, prevent normal bone marrow production. ATG, a medication that inhibits immune function, can restore normal blood production in some people with MDS, but it is not known how this happens and why it does not happen in all MDS patients. The purpose of this study is to examine the effects of ATG in adults with MDS and to determine which individuals with MDS are most likely to benefit from treatment with ATG.
Based on disease severity and likely disease progression, participants will be separated into either a high-risk group or a low-risk group. Participants will be hospitalized for a 4-day period during which they will receive daily infusions of ATG. Oral prednisone will be given 2 days before hospitalization, throughout hospitalization, and then for 14 days after hospitalization to limit the side effects of ATG. Antihistamines and acetaminophen will also be given during hospitalization to reduce the chances of an allergic reaction to ATG. After discharge, all participants will attend monthly study visits that will include blood collection, review of disease symptoms, and evaluation of medication response. At Week 16, participants in the high-risk group will undergo additional blood collection, a bone marrow biopsy, and a thorough evaluation of disease progression and the effects of MDS on daily living abilities. Participants in the low-risk group will undergo these same procedures at Week 24. Follow-up for all participants may last up to 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Antithymocyte globulin (ATG), Drug: PrednisoneParticipants will be treated with ATG |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosis of MDS that meets International Prognostic Scoring System (IPSS) criteria for low risk, intermediate-1 risk, or intermediate-2 risk. More information about this criterion can be found in the protocol.
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
- Willing and able to attend study visits
- Willing to use acceptable forms of contraception prior to study entry and for the duration of the study
Key exclusion criteria (12 listed)
- Any serious medical illness that might limit survival to less than 2 years
- Any other uncontrolled condition or illness. More information about this criterion can be found in the protocol.
- Prior anti-lymphocyte serotherapy (received serum from an immunized animal)
- Proliferative chronic myelomonocytic leukemia
- MDS that is caused by radiotherapy, chemotherapy, and/or immunotherapy for cancerous or autoimmune diseases
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 |
|---|---|---|
| Antithymocyte globulin (ATG)ATG 2.5 mg/kg/day via IV will be given for 4 doses. Each participant will receive only one cycle of therapy. The daily infusion will be administered over at least 6 hours and slowed as necessary to minimize infusion-related symptoms. | Drug | 1 |
| PrednisoneAll participants will be pre-treated with prednisone (1 mg/kg/day by mouth) 2 days prior to the first ATG does and continuing for 14 days after the final dose to prevent serum sickness | Drug | 1 |
Primary outcome
Bone marrow response and hematologic improvement
Time frame: Measured at Week 16 or 24
Bone marrow cytogenetic response
Time frame: Measured at Week 16 or 24
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2009.
- Background: PubMed 12393644Kochenderfer JN, Kobayashi S, Wieder ED, Su C, Molldrem JJ. Loss of T-lymphocyte clonal dominance in patients with myelodysplastic syndrome responsive to immunosuppression. Blood. 2002 Nov 15;100(10):3639-45. doi: 10.1182/blood-2002-01-0155. Epub 2002 Jul 5.
- Background: PubMed 11843844Maciejewski JP, Rivera C, Kook H, Dunn D, Young NS. Relationship between bone marrow failure syndromes and the presence of glycophosphatidyl inositol-anchored protein-deficient clones. Br J Haematol. 2001 Dec;115(4):1015-22. doi: 10.1046/j.1365-2141.2001.03191.x.
- Background: PubMed 12160363Molldrem JJ, Leifer E, Bahceci E, Saunthararajah Y, Rivera M, Dunbar C, Liu J, Nakamura R, Young NS, Barrett AJ. Antithymocyte globulin for treatment of the bone marrow failure associated with myelodysplastic syndromes. Ann Intern Med. 2002 Aug 6;137(3):156-63. doi: 10.7326/0003-4819-137-3-200208060-00007.
- Derived from this study: PubMed 24488560Komrokji RS, Mailloux AW, Chen DT, Sekeres MA, Paquette R, Fulp WJ, Sugimori C, Paleveda-Pena J, Maciejewski JP, List AF, Epling-Burnette PK. A phase II multicenter rabbit anti-thymocyte globulin trial in patients with myelodysplastic syndromes identifying a novel model for response prediction. Haematologica. 2014 Jul;99(7):1176-83. doi: 10.3324/haematol.2012.083345. Epub 2014 Jan 31.
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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.
Alan List, MD principal investigator
H. Lee Moffitt Cancer Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Antithymocyte globulin (ATG) and Prednisone in people with Myelodysplastic Syndrome, run by Office of Rare Diseases (ORD) at 4 sites 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?
The sponsor lists 4 inclusion and 12 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: status not confirmed, as of the sponsor's last update on 2 Jun 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bone marrow response and hematologic improvement (time frame: Measured at Week 16 or 24). 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 NCT00466843, which also lists 4 linked publications.
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 2 Jun 2009.