Myelodysplastic SyndromePhase 2NCT00005937

Antithymocyte Globulin and Cyclosporine to Treat Myelodysplasia

A Phase 2 study testing Antithymocyte globulin and Cyclosporine in people with Myelodysplastic Syndrome, run by Neal Young, M.D. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Myelodysplastic Syndrome
What is being tested?: Antithymocyte globulin and Cyclosporine
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 42 participants
Where: 1 siteUnited States
Study dates: Jun 2000to Mar 2008
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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

MDS of refractory anemia (RA), refractory anemia with ring sideroblasts (RARS) \& refractory anemia with excess blasts (RAEB) sub-types
Off all other treatments (except G-CSF (granulocyte colony stimulating factor), 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.
Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
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
ECOG performance status of greater than 2
Active uncontrolled infection

Show all 15Show fewer

Current pregnancy, or unwilling to take oral contraceptives 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 than18 years
Not able to 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 Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: A Phase II Study of Antithymocyte Globulin (ATG) and Cyclosporine to Treat the Cytopenia of Myelodysplastic Syndrome (MDS)

This study will determine the safety and effectiveness of a combination of the immune-suppressing drugs antithymocyte globulin (ATG) and cyclosporine for treating myelodysplasia, a disorder of low blood cell counts. It will: evaluate whether this drug combination can increase blood counts in patients and reduce their need for transfusions; compare survival of patients who respond to ATG and cyclosporine treatment with those who do not respond; and determine the side effects of the treatment.

Myelodysplasia is thought to result from an immune system abnormality in which cells called lymphocytes attack the marrow's blood-forming cells. The resulting deficiencies of platelets and red and white blood cells cause anemia, susceptibility to infections, and easy bruising and bleeding. Various therapies, such as blood transfusions for anemia and bleeding, antibiotics for infection, chemotherapy and bone marrow transplantation are used to treat myelodysplasia, but all have disadvantages and some carry serious risks.

Patients 18 years of age and older with myelodysplasia may be eligible for this study. Candidates will be screened with a physical examination and medical history, blood tests, chest X-ray, electrocardiogram and bone marrow biopsy (removal of a marrow sample from the hipbone for microscopic examination).

Read the detailed description

Participants will be admitted to the NIH Clinical Center for the first 10 to 14 days of treatment and will then continue therapy on an outpatient basis. They will undergo the following tests and procedures:

Placement of central line-An intravenous (IV) catheter (flexible tube inserted into a vein) is placed in a large vein of the neck, chest or arm. Medicines are delivered through this line and blood samples are drawn from it.
ATG skin testing- ATG is injected under the skin to check for sensitization to horse serum, from which the drug is derived.
ATG treatment-Four doses of ATG are given through the IV line on each of 4 consecutive days. Prednisone is taken by mouth beginning the first day of ATG therapy and continuing for a total of 17 days. This drug is given to reduce the side effects of ATG, such as fever, skin rash and chills.
Cyclosporine treatment- Cyclosporine capsules are taken by mouth twice a day for at least 6 months.

During hospitalization, blood will be drawn daily for blood counts and other tests. Upon the patient's discharge after 10 days, the referring physician will do blood tests weekly during the first month of treatment and then every 2 weeks for the rest of the time the patient is taking cyclosporine. Dosages of this drug may be adjusted depending on the test results. Patients will be evaluated at the NIH Clinical Center at 3-month intervals for the first year, then every 6 months for the next 3 years and then at yearly intervals. A blood sample will be drawn at each visit. Bone marrow biopsies will be done at 6-month intervals for the first 3 years after treatment.

A growing body of laboratory and clinical evidence suggests that the cytopenia of MDS is at least partly a result of cytotoxic T cell activity. Treatments to abrogate T cell activity such as anti-thymocyte globulin alone and cyclosporine alone have demonstrated varying degrees of success in alleviating the cytopenia of MDS. A response to such therapy in MDS is associated with improved survival. Experience with aplastic anemia suggests that the combination of these two agents should be more effective in suppressing cytotoxic T cell activity and alleviating cytopenia. This protocol proposes using the combination of antithymocyte globulin (ATG) and cyclosporine (CSA) to treat the cytopenia of MDS, in an effort to improve the response rate to immunosuppressive therapy in this disease.

Conditions: Myelodysplastic Syndrome
Being tested: Antithymocyte globulin, Cyclosporine
Keywords: MDS, Immunosuppression, ATG, Cyclosporine, Myelodysplastic Syndrome
Medical subject headings: Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Antithymocyte globulinDrug
Antithymocyte globulin (ATG) intravenous infusion: 40mg/kg/day. Infusion over 6 hours on day 1-4.
CyclosporineDrug
Cyclosporine (CsA) intravenous infusion: 5mg/kg. Infusion on day 14 administered twice a day.

Study groups in NCT00005937
Study group	Role	What they receive
Antithymocyte globulin & cyclosporine	Experimental	Myelodysplastic syndromes (MDS) subjects will be treated with Anti-thymocyte Globulin (ATG) and cyclosporine (CsA). The subjects will receive ATG at a dose of 40mg/kg orally on days 1-4 in combination with oral prednisone at a dose of 1mg/kg/day on day one. The prednisone will be tapered on day 10. The taper schedule will be every two days over a total of eight days (days 10-17). Drug the ATG administration the subjects will receive at least 4 units of platelets daily for platelet counts less than 20,000/ microliters. Cyclosporine (CsA) will be started on day 14 at a dose of 5mg/kg twice daily with dose adjustments based on drug levels (target 200-400 ng/ml). Cyclosporine therapy will be continued for six months. Receives: Drug: Antithymocyte globulin; Drug: Cyclosporine

What is being measured

The primary outcome is the main question the study is designed to answer.

Red Blood Cell Transfusion Independence
Red blood cell transfusion independence was documented as time from last transfusion of red cells to last day of transfusion free follow-up. Independence or response to the intervention was assessed by weekly blood counts. Transfusion independence was defined as no transfusion requirement for a 3 month period. Complete hematologic response is defined as the normalization of affected cells lines and less than 5% marrow blasts present. Partial hematologic response is defined as greater than 50% improvement from baseline to normal levels of all cell counts and greater than 50% decrease in marrow blasts.
Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2000Mar 2008

First posted7 Jul 2000 (estimated)
Study startJun 2000
Primary completionMar 2008
Study completionMar 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 42 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00005937
Sponsor's protocol ID: 000169
Other IDs: 00-H-0169
Status last verified: Oct 2014
First submitted: 6 Jul 2000
Last updated: 23 Oct 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Bynoe AG, Scott CS, Ford P, Roberts BE. Decreased T helper cells in the myelodysplastic syndromes. Br J Haematol. 1983 May;54(1):97-102. doi: 10.1111/j.1365-2141.1983.tb02071.x.
PubMed 6221751
Porta F, Facchetti F, Tettoni K, Laffranchi MG, Arrighini A, Ugazio AG. Myelodysplastic syndrome in an infant: induction of remission by cyclosporin. Lancet. 1998 Nov 14;352(9140):1600-1. doi: 10.1016/s0140-6736(05)61048-3. No abstract available.
PubMed 9843114
Nydegger 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
Mehta SD, Moses S, Agot K, Maclean I, Odoyo-June E, Li H, Bailey RC. Medical male circumcision and herpes simplex virus 2 acquisition: posttrial surveillance in Kisumu, Kenya. J Infect Dis. 2013 Dec 1;208(11):1869-76. doi: 10.1093/infdis/jit371. Epub 2013 Jul 30.
PubMed 23901089

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 1/2
Omacetaxine + Azacitidine in Untreated Patients With High Grade MDS
High Grade Myelodysplastic Syndromes
RecruitingPhase 1/2
Pacritinib, a Kinase Inhibitor of CSF1R, IRAK1, JAK2, and FLT3, in Adults and Pediatric Participants 12 Years of Age or Older With Myelodysplastic Syndromes or Myelodysplastic/Myeloproliferative Neoplasms
Myelodysplastic Syndromes
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome

All Myelodysplastic Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 23 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase II Study of Antithymocyte Globulin (ATG) and Cyclosporine to Treat the Cytopenia of Myelodysplastic Syndrome (MDS)
ClinicalTrials.gov ID: NCT00005937
Acronym / sponsor ID: 000169
Conditions: Myelodysplastic Syndrome
Keywords: MDS, Immunosuppression, ATG, Cyclosporine, Myelodysplastic Syndrome
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 42 participants (actual)
Lead sponsor: Neal Young, M.D.US National Institutes of Health
Study start: Jun 2000
Primary completion: Mar 2008 (actual)
Study completion: Mar 2008 (actual)
First posted: 7 Jul 2000 (estimated)
Results: Posted 23 Oct 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Placement of central line-An intravenous (IV) catheter (flexible tube inserted into a vein) is placed in a large vein of the neck, chest or arm. Medicines are delivered through this line and blood samples are drawn from it.
ATG skin testing- ATG is injected under the skin to check for sensitization to horse serum, from which the drug is derived.
ATG treatment-Four doses of ATG are given through the IV line on each of 4 consecutive days. Prednisone is taken by mouth beginning the first day of ATG therapy and continuing for a total of 17 days. This drug is given to reduce the side effects of ATG, such as fever, skin rash and chills.
Cyclosporine treatment- Cyclosporine capsules are taken by mouth twice a day for at least 6 months.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Antithymocyte globulin & cyclosporine	Experimental	Drug: Antithymocyte globulin, Drug: CyclosporineMyelodysplastic syndromes (MDS) subjects will be treated with Anti-thymocyte Globulin (ATG) and cyclosporine (CsA). The subjects will receive ATG at a dose of 40mg/kg orally on days 1-4 in combination with oral prednisone at a dose of 1mg/kg/day on day one. The prednisone will be tapered on day 10. The taper schedule will be every two days over a total of eight days (days 10-17). Drug the ATG administration the subjects will receive at least 4 units of platelets daily for platelet counts less than 20,000/ microliters. Cyclosporine (CsA) will be started on day 14 at a dose of 5mg/kg twice daily with dose adjustments based on drug levels (target 200-400 ng/ml). Cyclosporine therapy will be continued for six months.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

MDS of refractory anemia (RA), refractory anemia with ring sideroblasts (RARS) \& refractory anemia with excess blasts (RAEB) sub-types
Off all other treatments (except G-CSF (granulocyte colony stimulating factor), 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.
Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
High or intermediate predicted probability of response

Key exclusion criteria (15 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
ECOG performance status of greater than 2

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 globulinAntithymocyte globulin (ATG) intravenous infusion: 40mg/kg/day. Infusion over 6 hours on day 1-4.	Drug	Antithymocyte globulin & cyclosporine
CyclosporineCyclosporine (CsA) intravenous infusion: 5mg/kg. Infusion on day 14 administered twice a day.	Drug	Antithymocyte globulin & cyclosporine

Primary outcome

Red Blood Cell Transfusion Independence
Time frame: 6 months
Red blood cell transfusion independence was documented as time from last transfusion of red cells to last day of transfusion free follow-up. Independence or response to the intervention was assessed by weekly blood counts. Transfusion independence was defined as no transfusion requirement for a 3 month period. Complete hematologic response is defined as the normalization of affected cells lines and less than 5% marrow blasts present. Partial hematologic response is defined as greater than 50% improvement from baseline to normal levels of all cell counts and greater than 50% decrease in marrow blasts.

Results and safety

Results posted to the registry on 23 Oct 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
MDS Subjects Treated With ATG & CsA	42	37

Primary outcome: Red Blood Cell Transfusion Independence

Time frame: 6 months. Number. Unit: participants

Measure	MDS Subjects Treated With ATG and CsA n = 37
Complete hematologic response	6
Partial hematologic response	10
No hematologic response	21

Adverse events

Other adverse events reported at 4.76% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
MDS Subjects Treated With ATG and CsA	11 of 42 (26.2%)	2 of 42 (4.8%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 6221751Bynoe AG, Scott CS, Ford P, Roberts BE. Decreased T helper cells in the myelodysplastic syndromes. Br J Haematol. 1983 May;54(1):97-102. doi: 10.1111/j.1365-2141.1983.tb02071.x.
Background: PubMed 9843114Porta F, Facchetti F, Tettoni K, Laffranchi MG, Arrighini A, Ugazio AG. Myelodysplastic syndrome in an infant: induction of remission by cyclosporin. Lancet. 1998 Nov 14;352(9140):1600-1. doi: 10.1016/s0140-6736(05)61048-3. No abstract available.
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.
Derived from this study: PubMed 23901089Mehta SD, Moses S, Agot K, Maclean I, Odoyo-June E, Li H, Bailey RC. Medical male circumcision and herpes simplex virus 2 acquisition: posttrial surveillance in Kisumu, Kenya. J Infect Dis. 2013 Dec 1;208(11):1869-76. doi: 10.1093/infdis/jit371. Epub 2013 Jul 30.
NIH Clinical Center Detailed Web PageLink provided by the sponsor.

Related trials for Myelodysplastic Syndrome

RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 1/2
Omacetaxine + Azacitidine in Untreated Patients With High Grade MDS
High Grade Myelodysplastic Syndromes
RecruitingPhase 1/2
Pacritinib, a Kinase Inhibitor of CSF1R, IRAK1, JAK2, and FLT3, in Adults and Pediatric Participants 12 Years of Age or Older With Myelodysplastic Syndromes or Myelodysplastic/Myeloproliferative Neoplasms
Myelodysplastic Syndromes
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome

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.

Neal Young, MD principal investigator

NIH National Heart, Lung, and Blood Institute

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 Antithymocyte globulin and Cyclosporine in people with Myelodysplastic Syndrome, run by Neal Young, M.D. 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 5 inclusion and 15 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 23 Oct 2014. 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?

Yes. Results are posted in the registry (first posted 23 Oct 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Red Blood Cell Transfusion Independence (time frame: 6 months). 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 NCT00005937, 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 23 Oct 2014.