Antithymocyte Globulin and Cyclosporine to Treat Myelodysplasia

NCT00005937 | Completed Phase 2 Results DMC

• 2 other identifiers: 00016900-H-0169
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Myelodysplastic Syndrome

Keywords

MDS; Immunosuppression; ATG; Cyclosporine; Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• 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.

  6 months

Study Arms (1)

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.

Drug: Antithymocyte globulin; Drug: Cyclosporine

Interventions

Antithymocyte globulin DRUG

Antithymocyte globulin (ATG) intravenous infusion: 40mg/kg/day. Infusion over 6 hours on day 1-4.

Antithymocyte globulin & cyclosporine

Cyclosporine DRUG

Cyclosporine (CsA) intravenous infusion: 5mg/kg. Infusion on day 14 administered twice a day.

Antithymocyte globulin & cyclosporine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Neal Young, M.D.: lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• 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.

  PMID: 6221751 BACKGROUND

• 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.

  PMID: 9843114 BACKGROUND

• 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.

  PMID: 3888832 BACKGROUND

• 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.

  PMID: 23901089 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Antilymphocyte Serum; Cyclosporine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides

Results Point of Contact

• Title: Neal S. Young MD
• Organization: NIH National Heart, Lung and Blood Institute

youngns@nhlbi.nih.gov

301-402-1806

Study Officials

• Neal Young, MD

  NIH National Heart, Lung, and Blood Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: NHLBI Hematolgy Branch Chief

Study Record Dates

• First Submitted: July 6, 2000
• First Posted: July 7, 2000
• Study Start: June 1, 2000
• Primary Completion: March 1, 2008
• Study Completion: March 1, 2008
• Last Updated: October 23, 2014
• Results First Posted: October 23, 2014

Record last verified: 2014-10

Locations

US (1)