Clinical trial NCT00017550: Antithymocyte Globulin Compared With Supportive Care in Treating Patients With Myelodysplastic Syndrome
Official title: An Open Label, Prospective, Stratified, Randomized, Controlled, Multi-Center, Phase IIB Study of the Impact of Thymoglobulin Therapy on Transfusion Needs of Patients With Early Myelodysplastic Syndrome (MDS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myelodysplastic Syndromes
Keywords: refractory anemia
refractory anemia with excess blasts
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Immunosuppressive therapy may improve bone marrow abnormalities and may be effective treatment for myelodysplastic syndrome. It is not yet known whether immunosuppressive therapy is more effective than supportive care in treating myelodysplastic syndrome.

PURPOSE: Randomized phase II trial to compare the effectiveness of antithymocyte globulin with that of supportive care in treating patients who have myelodysplastic syndrome.

Detailed description: OBJECTIVES:

* Compare the clinical response rate of patients with early myelodysplastic syndrome treated with rabbit anti-thymocyte globulin vs standard supportive care.
* Evaluate the safety of anti-thymocyte globulin in these patients.
* Compare the time to and duration of clinical response, rates of partial response and therapy failure, and rate of disease progression in patients treated with these regimens.
* Compare the ECOG performance score, number of transfusions and/or growth factor use, and maximum time between transfusions in patients treated with these regimens.
* Compare the infection risk, use of medical resources, and quality of clinical response in patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to myelodysplastic syndrome (MDS) subtype (refractory anemia (RA) vs RA with excess blasts or hypocellular MDS). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive rabbit anti-thymocyte globulin (ATG) IV over at least 8-12 hours on days 1-4.
* Arm II: Patients receive standard supportive therapy for 6 months. At the end of 6 months, patients may receive ATG as in arm I.

Patients are followed for 6 months.

PROJECTED ACCRUAL: A total of 72 patients (48 in arm I and 24 in arm II) will be accrued within a minimum of 6 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed early myelodysplastic syndrome (MDS) with less than 10% bone marrow blasts

  * Refractory anemia (RA)
  * RA with excess blasts (RAEB)
  * Hypocellular myelodysplasia
* Low or intermediate-1 prognostic risk
* Transfusion-dependent

  * Need for 2 or more units of red blood cells or platelets per month for 2 or more months prior to study OR
  * History of prior transfusions and 2 consecutive (at least 21 days apart) hemoglobin levels less than 8.0 g/dL or platelet counts less than 20,000/mm\^3 during the past 2 months

    * Hemoglobin no greater than 12.0 g/dL after prior transfusion
* No myelosclerosis occupying more than 30% of bone marrow space
* No RA with ringed sideroblasts, RAEB in transformation, or chronic myelomonocytic leukemia
* No therapy-related MDS
* No history of immune-related hematologic disorder (e.g., idiopathic thrombocytopenic purpura)

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* ECOG 0-2

Life expectancy:

* At least 3 months

Hematopoietic:

* See Disease Characteristics
* No other causes of cytopenia unrelated to MDS (e.g., gastrointestinal blood loss)
* Iron present on marrow examination OR
* Transferrin saturation at least 20% and ferritin at least 50 ng/mL

Hepatic:

* Bilirubin no greater than 2 mg/dL OR
* SGOT/SGPT no greater than 2 times normal
* No active or chronic hepatitis B or C

Renal:

* Creatinine no greater than 2 mg/dL

Cardiovascular:

* No symptomatic cardiac disease
* No congestive heart failure (even if medically controlled)
* No myocardial infarction within the past 6 months

Pulmonary:

* No severe pulmonary disease
* If history of pulmonary insufficiency, must have pO_2 at least 90 mm/Hg on room air or pCO_2 no greater than 40 mm/Hg

Other:

* No history of unresolved B12 or folate deficiency since diagnosis of MDS
* No untreated acute or chronic infection (afebrile for 7 days without antibiotics prior to study)
* No active or chronic HIV
* No concurrent cytomegalovirus infection
* No other malignancy within the past 2 years except adequately treated localized squamous cell or basal cell skin cancer or carcinoma in situ of the cervix
* No concurrent drug or alcohol abuse
* No significant medical or psychosocial problems
* No known allergy to rabbit protein
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* At least 8 weeks since prior biologic agents, colony-stimulating factors, or epoetin alfa for MDS
* At least 8 weeks since other prior investigational biologic agents
* No prior or concurrent bone marrow transplantation
* No concurrent epoetin alfa
* No concurrent growth factors except filgrastim (G-CSF) or sargramostim (GM-CSF) for neutropenic fevers
* No other concurrent biologic agents

Chemotherapy:

* At least 8 weeks since prior cytotoxic drugs for MDS
* Concurrent chemotherapy for clinical indications of disease progression or leukemic transformation allowed

Endocrine therapy:

* At least 8 weeks since prior androgenic hormonal therapy for MDS
* At least 8 weeks since prior danazol for MDS

Radiotherapy:

* No prior radiotherapy

Surgery:

* No prior organ transplantation

Other:

* At least 8 weeks since prior investigational drugs
* At least 8 weeks since prior immunosuppressive drugs or other drugs for MDS
* No concurrent immunosuppressive therapy
* No other concurrent experimental drugs

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Washington
country: United States
facility: Washington Cancer Institute
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida Health Science Center
state: Florida
city: Miami
country: United States
facility: Sylvester Cancer Center, University of Miami
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Tampa
country: United States
facility: Veterans Affairs Medical Center - Tampa (Haley)
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Chicago
country: United States
facility: Rush Cancer Institute
state: Illinois
city: Beech Grove
country: United States
facility: Indiana Blood and Marrow Transplant
state: Indiana
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: New Orleans
country: United States
facility: Tulane University School of Medicine
state: Louisiana
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Kansas City
country: United States
facility: University of Missouri Kansas City School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis University Cancer Center
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: New York Presbyterian Hospital - Cornell Campus
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center, NY
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center at Wake Forest University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Dallas
country: United States
facility: Texas Oncology P.A.
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Calgary
country: Canada
facility: Foothills Hospital
state: Alberta
city: Vancouver
country: Canada
facility: Department of Medicine
state: British Columbia
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: Sangstat Medical Corporation
name: Elizabeth C. Squiers, MD
role: STUDY_CHAIR
References: