A Randomized Trial of Recombinant Humanized Anti-IL-2 Receptor Antibody (Daclizumab) Versus Antithymocyte Globulin (ATG) to Treat the Cytopenia of Myelodysplastic Syndrome (MDS)

NCT00072969 | Completed Phase 2

• 2 other identifiers: 04002604-H-0026
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Myelodysplastic Syndromes

Keywords

Immunosuppression; Myelodysplastic Syndrome; MDS

Interventions

Daclizumab DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• thrombocytopenia (platelet count less than 50000/ul)
• neutropenia (absolute neutrophil count less than 500/ul).
• 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

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
• 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
• 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

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Heart, Lung and Blood Institute (NHLBI)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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.

  PMID: 9488617 BACKGROUND

• Biesma 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.

  PMID: 9118037 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

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Daclizumab

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 12, 2003
• First Posted: November 13, 2003
• Study Start: November 1, 2003
• Study Completion: August 1, 2005
• Last Updated: March 4, 2008

Record last verified: 2005-08

Locations

US (1)