Myelodysplastic SyndromesPhase 2NCT00072969
A Randomized Trial of Recombinant Humanized Anti-IL-2 Receptor Antibody (Daclizumab) Versus Antithymocyte Globulin (ATG) to Treat the Cytopenia of Myelodysplastic Syndrome (MDS)
A Phase 2 study testing Daclizumab in people with Myelodysplastic Syndromes, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
This study will evaluate a new immunosupressive therapy, Daclizumab, and compare it with antithymocyte globulin (ATG) to treat cytopenia, that is, the deficiency of cellular elements of the blood, in myelodysplastic syndrome (MDS). Daclizumab is an anti-interleukin-2 receptor (IL-2) antibody. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Myelodysplastic Syndromes
- What is being tested?
- Daclizumab
- How many people
- 132 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2003to Aug 2005
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- MDS of RA, RARS \& RAEB sub-types including those previously treated with chemotherapy or experimental agents such as retinoids, Vitamin D, and growth factors
- Anemia requiring transfusion support with at least one unit of packed red blood cells per month for greater than or equal to 2 months
- OR
- thrombocytopenia (platelet count less than 50000/ul)
- OR
- neutropenia (absolute neutrophil count less than 500/ul).
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- Off all other treatments (except G-CSF, and transfusion support and related medications) for at least four weeks. G-CSF can be used before, during and after the protocol treatment for patients with documented neutropenia (less than 500/Ul) as long as they meet the criteria for anemia and/or thrombocytopenia as stated above.
- ECOG performance status less than or equal to 2
- High or intermediate predicted probability of response
Who cannot join
- MDS of FAB sub-group chronic myelomonocytic leukemia (CMML)
- Transformation to acute leukemia (FAB sub-group RAEB-T, ie, greater than 20% blasts in marrow aspirate)
- Hypoplastic marrow without one major or two minor criteria
- Treatment with growth factors (except for G-CSF) or cyclosporine within 4 weeks prior to entry to protocol
- Recent or current treatment (24 hours wash out period) with the herbal supplement Echinacea purpurea or Usnea barbata (Old Man's Beard)
- ECOG performance status of greater than 2
Show all 16Show fewer
- Active uncontrolled infection (chronic or current clinically significant infection, including hepatitis B or C virus infection)
- Current pregnancy, or unwilling to take oral contraceptives or refrain from pregnancy if of childbearing potential
- Patients for whom bone marrow transplant is indicated as standard therapy (age less than fifty-five with a fully-matched sibling donor)
- Age less than 18 years
- Not able to understand the investigational nature of the study or give informed consent
- HIV positive patients
- Active malignant disease (excluding basal cell carcinoma)
- Serum creatinine greater than 2mg/dl
- Patients who are moribund or patients with concurrent hepatic, renal, cardiac, metabolic, or any disease of such severity that death within 3 months is likely
- Low predicted probability of response
Trial locations and contacts
1 site in 1 country.
United States1 site
National Heart, Lung and Blood Institute (NHLBI)
Bethesda, Maryland, 20892
About this study
This study will evaluate a new immunosupressive therapy, Daclizumab, and compare it with antithymocyte globulin (ATG) to treat cytopenia, that is, the deficiency of cellular elements of the blood, in myelodysplastic syndrome (MDS). Daclizumab is an anti-interleukin-2 receptor (IL-2) antibody. MDS, also known as myelodysplasia, is a disorder that can cause anemia, spontaneous bleeding, and greater risk of infections. Although the bone marrow can still produce some blood cells, very few reach the bloodstream. The cause of MDS is not known, although its behavior is. Many patients need transfusions of red blood cells. They may also develop leukemia, which is often quite resistant to treatment with chemotherapy. However, the progression of the disorder to leukemia is usually slow, taking many years.
Patients 18 years of age and older who have MDS may be eligible for this study. Participants will undergo the following tests and procedures:
Read more
- Medical history and physical examination.
- Collection of blood for tests including blood counts, liver and kidney function, and antibodies against common viruses.
- Chest x-ray.
- Electrocardiogram.
- Bone marrow sample to confirm the diagnosis.
Participants will randomly receive either ATG or Daclizumab. If they are in the group to receive ATG, they will be admitted as inpatients to undergo the first 10 to 14 days of treatment. If they do not already have a catheter in one of the large veins of the neck, chest, or arm, one will be placed. ATG will be given through the catheter. Blood counts and other blood analysis will be monitored daily while the patients are treated. After about 10 days, they will be released, to be under the care of their referring physicians. Those participants who are in the group to receive Daclizumab will receive a total of five doses, one every 2 weeks, over 8 weeks, given through a vein as a 15-minute infusion. The first, third, and fifth dose will be given at the outpatient clinic. The second and fourth doses can be given either at the clinic or by the patients' primary hematologists.
All patients will be followed as outpatients at 3-month intervals for the first year, and then every 6 months for the next 3 years. Afterward, follow-up will be yearly. A small sample of blood will be drawn at the visits. Also, bone marrow examinations will be requested at the 6-month intervals for the first 3 years of treatment. If the treatment that patients are assigned to does not work, after 6 months, they will be eligible to receive the other treatment-provided that they have complied with the required blood tests and visits to the clinic required to assess the patients' safety.
Read the detailed description
Many bone marrow failure syndromes in humans are now recognized to result from immunological mechanisms. These diseases include aplastic anemia, pure red cell aplasia, and some types of myelodysplasia. Patients with these conditions, who may suffer variable degrees of anemia, leukocytopenia, and thrombocytopenia, alone or in combination, have been shown to respond to a wide variety of immunosuppressive agents, ranging from corticosteroids to cyclosporine (CSA) and antithymocyte globulin (ATG), however, nonresponse and relapse continues to be a problem. Why some patients do not respond initially or others respond and then relapse is unclear. Autoreactive T cells may be resistant to the effect of ATG/CsA (nonresponders), while in others residual autoreactive T cells expand post-treatment leading to hematopoietic stem cell destruction and recurrent pancytopenia (relapse). Therefore, novel, less toxic immunosuppressive regimens that increase response rates and hematologic recovery and decrease relapse rates are needed.
One such novel therapy, Daclizumab, a humanized anti-interleukin-2 receptor (lL-2R) monoclonal antibody (mAb), acts against activated lymphocytes, thus sharing an important mechanism of action with ATG. The mAb is much less toxic than ATG and may be administered to outpatients at relatively infrequent intervals (every 2 weeks). Treatments with ATG alone and CsA alone have demonstrated varying degrees of success in alleviating the cytopenia of MDS. Our experience suggests that ATG rather than CSA is the more effective agent inducing hematological responses in susceptible MDS patients and that certain variables including the patient's age, whether or not they were HLA DR15, and days of red cell transfusion dependence prior to treatment were predictive of response.
We therefore propose this randomized phase II study to evaluate and compare a new immunosuppressive therapy, Daclizumab, with antithymocyte globulin (ATG) to treat the cytopenia of MDS in a population of subjects with intermediate or high predicted probability of response.
- Conditions
- Myelodysplastic Syndromes
- Being tested
- Daclizumab
- Keywords
- Immunosuppression, Myelodysplastic Syndrome, MDS
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DaclizumabDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2003 (estimated)
- Study startNov 2003
- Study completionAug 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The 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 2
- Primary purpose
- Treatment
- Enrolment
- 132 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00072969
- Sponsor's protocol ID
- 040026
- Other IDs
- 04-H-0026
- Status last verified
- Aug 2005
- First submitted
- 12 Nov 2003
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Jonasova A, Neuwirtova R, Cermak J, Vozobulova V, Mocikova K, Siskova M, Hochova I. Cyclosporin A therapy in hypoplastic MDS patients and certain refractory anaemias without hypoplastic bone marrow. Br J Haematol. 1998 Feb;100(2):304-9. doi: 10.1046/j.1365-2141.1998.00551.x.
PubMed 9488617Biesma DH, van den Tweel JG, Verdonck LF. Immunosuppressive therapy for hypoplastic myelodysplastic syndrome. Cancer. 1997 Apr 15;79(8):1548-51. doi: 10.1002/(sici)1097-0142(19970415)79:83.0.co;2-y.
PubMed 9118037Nydegger UE. Suppressive and substitutive immunotherapy: an essay with a review of recent literature. Immunol Lett. 1985;9(4):185-90. doi: 10.1016/0165-2478(85)90031-8. No abstract available.
PubMed 3888832
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Trial of Recombinant Humanized Anti-IL-2 Receptor Antibody (Daclizumab) Versus Antithymocyte Globulin (ATG) to Treat the Cytopenia of Myelodysplastic Syndrome (MDS)
- ClinicalTrials.gov ID
- NCT00072969
- Acronym / sponsor ID
- 040026
- Conditions
- Myelodysplastic Syndromes
- Keywords
- Immunosuppression, Myelodysplastic Syndrome, MDS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 132 participants
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- Nov 2003
- Study completion
- Aug 2005
- First posted
- 13 Nov 2003 (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.
This study will evaluate a new immunosupressive therapy, Daclizumab, and compare it with antithymocyte globulin (ATG) to treat cytopenia, that is, the deficiency of cellular elements of the blood, in myelodysplastic syndrome (MDS). Daclizumab is an anti-interleukin-2 receptor (IL-2) antibody. MDS, also known as myelodysplasia, is a disorder that can cause anemia, spontaneous bleeding, and greater risk of infections. Although the bone marrow can still produce some blood cells, very few reach the bloodstream. The cause of MDS is not known, although its behavior is. Many patients need transfusions of red blood cells. They may also develop leukemia, which is often quite resistant to treatment with chemotherapy. However, the progression of the disorder to leukemia is usually slow, taking many years.
Patients 18 years of age and older who have MDS may be eligible for this study. Participants will undergo the following tests and procedures:
- Medical history and physical examination.
- Collection of blood for tests including blood counts, liver and kidney function, and antibodies against common viruses.
- Chest x-ray.
- Electrocardiogram.
- Bone marrow sample to confirm the diagnosis.
Participants will randomly receive either ATG or Daclizumab. If they are in the group to receive ATG, they will be admitted as inpatients to undergo the first 10 to 14 days of treatment. If they do not already have a catheter in one of the large veins of the neck, chest, or arm, one will be placed. ATG will be given through the catheter. Blood counts and other blood analysis will be monitored daily while the patients are treated. After about 10 days, they will be released, to be under the care of their referring physicians. Those participants who are in the group to receive Daclizumab will receive a total of five doses, one every 2 weeks, over 8 weeks, given through a vein as a 15-minute infusion. The first, third, and fifth dose will be given at the outpatient clinic. The second and fourth doses can be given either at the clinic or by the patients' primary hematologists.
All patients will be followed as outpatients at 3-month intervals for the first year, and then every 6 months for the next 3 years. Afterward, follow-up will be yearly. A small sample of blood will be drawn at the visits. Also, bone marrow examinations will be requested at the 6-month intervals for the first 3 years of treatment. If the treatment that patients are assigned to does not work, after 6 months, they will be eligible to receive the other treatment-provided that they have complied with the required blood tests and visits to the clinic required to assess the patients' safety.
Detailed description
Many bone marrow failure syndromes in humans are now recognized to result from immunological mechanisms. These diseases include aplastic anemia, pure red cell aplasia, and some types of myelodysplasia. Patients with these conditions, who may suffer variable degrees of anemia, leukocytopenia, and thrombocytopenia, alone or in combination, have been shown to respond to a wide variety of immunosuppressive agents, ranging from corticosteroids to cyclosporine (CSA) and antithymocyte globulin (ATG), however, nonresponse and relapse continues to be a problem. Why some patients do not respond initially or others respond and then relapse is unclear. Autoreactive T cells may be resistant to the effect of ATG/CsA (nonresponders), while in others residual autoreactive T cells expand post-treatment leading to hematopoietic stem cell destruction and recurrent pancytopenia (relapse). Therefore, novel, less toxic immunosuppressive regimens that increase response rates and hematologic recovery and decrease relapse rates are needed.
One such novel therapy, Daclizumab, a humanized anti-interleukin-2 receptor (lL-2R) monoclonal antibody (mAb), acts against activated lymphocytes, thus sharing an important mechanism of action with ATG. The mAb is much less toxic than ATG and may be administered to outpatients at relatively infrequent intervals (every 2 weeks). Treatments with ATG alone and CsA alone have demonstrated varying degrees of success in alleviating the cytopenia of MDS. Our experience suggests that ATG rather than CSA is the more effective agent inducing hematological responses in susceptible MDS patients and that certain variables including the patient's age, whether or not they were HLA DR15, and days of red cell transfusion dependence prior to treatment were predictive of response.
We therefore propose this randomized phase II study to evaluate and compare a new immunosuppressive therapy, Daclizumab, with antithymocyte globulin (ATG) to treat the cytopenia of MDS in a population of subjects with intermediate or high predicted probability of response.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- MDS of RA, RARS \& RAEB sub-types including those previously treated with chemotherapy or experimental agents such as retinoids, Vitamin D, and growth factors
- Anemia requiring transfusion support with at least one unit of packed red blood cells per month for greater than or equal to 2 months
- OR
- thrombocytopenia (platelet count less than 50000/ul)
- OR
Key exclusion criteria (16 listed)
- MDS of FAB sub-group chronic myelomonocytic leukemia (CMML)
- Transformation to acute leukemia (FAB sub-group RAEB-T, ie, greater than 20% blasts in marrow aspirate)
- Hypoplastic marrow without one major or two minor criteria
- Treatment with growth factors (except for G-CSF) or cyclosporine within 4 weeks prior to entry to protocol
- Recent or current treatment (24 hours wash out period) with the herbal supplement Echinacea purpurea or Usnea barbata (Old Man's Beard)
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 |
|---|---|---|
| Daclizumab | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 9488617Jonasova A, Neuwirtova R, Cermak J, Vozobulova V, Mocikova K, Siskova M, Hochova I. Cyclosporin A therapy in hypoplastic MDS patients and certain refractory anaemias without hypoplastic bone marrow. Br J Haematol. 1998 Feb;100(2):304-9. doi: 10.1046/j.1365-2141.1998.00551.x.
- Background: PubMed 9118037Biesma DH, van den Tweel JG, Verdonck LF. Immunosuppressive therapy for hypoplastic myelodysplastic syndrome. Cancer. 1997 Apr 15;79(8):1548-51. doi: 10.1002/(sici)1097-0142(19970415)79:83.0.co;2-y.
- Background: PubMed 3888832Nydegger UE. Suppressive and substitutive immunotherapy: an essay with a review of recent literature. Immunol Lett. 1985;9(4):185-90. doi: 10.1016/0165-2478(85)90031-8. No abstract available.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Daclizumab in people with Myelodysplastic Syndromes, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site 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 9 inclusion and 16 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: finished, as of the sponsor's last update on 4 Mar 2008. 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 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00072969, which also lists 3 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 4 Mar 2008.