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


Phase 2
N/A
N/A
Not Enrolling
Both
Myelodysplastic Syndromes

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Trial Information

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


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.

Inclusion Criteria


INCLUSION CRITERIA:

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).

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

EXCLUSION CRITERIA:

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

Low predicted probability of response

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment

Authority:

United States: Federal Government

Study ID:

040026

NCT ID:

NCT00072969

Start Date:

November 2003

Completion Date:

August 2005

Related Keywords:

  • Myelodysplastic Syndromes
  • Immunosuppression
  • Myelodysplastic Syndrome
  • MDS
  • Myelodysplastic Syndromes
  • Preleukemia

Name

Location
National Heart, Lung and Blood Institute (NHLBI) Bethesda, Maryland  20892