Thymoglobulin and Cyclosporine in Patients With Aplastic Anemia or Myelodysplastic Syndrome

This study has been completed.
Sponsor:
Collaborator:
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00806598
First received: December 9, 2008
Last updated: March 8, 2013
Last verified: March 2013
  Purpose

The goal of this clinical research study is to learn if combining the drugs thymoglobulin, methylprednisolone, cyclosporine, and G-CSF (NeupogenTM or NeulastaTM ) can help to control severe aplastic anemia (AA) or hypoplastic myelodysplastic syndrome (MDS). The safety of this combination therapy will also be studied.


Condition Intervention Phase
Myelodysplastic Syndrome
Aplastic Anemia
Drug: Thymoglobulin
Drug: Cyclosporine
Drug: Methylprednisolone
Drug: G-CSF
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Combination of Thymoglobulin, Cyclosporine, Methylprednisone, and Granulocyte Colony-stimulating Factor (GCSF) in Patients With Newly Diagnosed Aplastic Anemia or With Hypoplastic or Low/Intermediate-1 Risk Myelodysplastic Syndrome

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Overall Response [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first. Assessed first at 3 months on study, continuing monthly up to 3 years. ] [ Designated as safety issue: No ]
    Complete response (CR) was defined as normalization of peripheral blood and bone marrow with <5% blasts, a peripheral absolute neutrophil count (ANC) >/= 1 * 10^9/l, hemoglobin >/= 100g/l, and a platelet count >/= * 10^9/l, Partial Response (PR) was defined as transfusion independence with a peripheral blood ANC >=/ 0.05 * 10^9/l, a platelet count >/= 20 * 10^9/l, and a hemoglobin >/= 40 g/l. Hematologic improvement was defined as a clinically relevant increase in hemoglobin, platelets or absolute neutrophil count.


Enrollment: 53
Study Start Date: May 2005
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Thymoglobulin + Cyclosporin
Combination of Thymoglobulin 3.5 or 2.5 mg/kg/day intravenous (IV) for 5 days + Methylprednisone 1 mg/kg/day IV for 5 days, before each dose Thymoglobulin + Cyclosporin 5 mg/kg orally for 6 months following Thymoglobulin + Granulocyte - Colony Stimulating Factor (G-CSF) 5 microgram/kg subcutaneously daily up to 3 months
Drug: Thymoglobulin

3.5 or 2.5 mg/kg/day IV for 5 days

  • Aplastic anemia patients receive 3.5 mg/kg/day for 5 days
  • MDS patients <55 years receive 3.5 mg/kg/day for 5 days
  • MDS patients >55 years receive 2.5 mg/kg/day for 5 days
Other Names:
  • ATG
  • Antithymocyte globulin
Drug: Cyclosporine
5 mg/kg orally for 6 months; start after completing thymoglobulin.
Other Names:
  • CYA
  • Sandimmune
  • Cyclosporine A
Drug: Methylprednisolone
1 mg/kg/day IV for 5 days, given before each dose of thymoglobulin.
Other Names:
  • Duralone®
  • Medralone®
  • Medrol®
  • M-Prednisol®
  • Solu-Medrol®
Drug: G-CSF
5 microgram/kg subcutaneously daily up to 3 months, start after thymoglobulin.
Other Names:
  • Neupogen®
  • Granulocyte - Colony Stimulating Factor

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of severe aplastic anemia (bone marrow cellularity < 30%, with two of three peripheral counts at the time of initial presentation or currently low with absolute neutrophil count (ANC) < 500/mL, pre-transfusion platelet (PLT) < 20,000/mL, or pre-transfusion hemoglobin < 8 g/dL and presence of no other underlying disorder.
  • Diagnosis of MDS (World Health Organization) with bone marrow cellularity < 30%, with two of three peripheral counts at the time of initial presentation or currently low with ANC < 500/mL, pre-transfusion PLT < 20,000/mL, or pre-transfusion hemoglobin < 8 g/dL.
  • Patients with MDS who have received prior biological therapy (not chemotherapy) are eligible. Hypomethylating agents and histone deacetylase inhibitors are considered as biological therapy.
  • Age 15 or greater
  • Adequate renal function (creatinine less than or equal to 2.0 mg/dL) unless related to the disease
  • Adequate hepatic function (bilirubin less than or equal to 3.5 mg/dL) unless related to the disease
  • No other investigational therapy in the past 14 days
  • Able to sign consent form
  • Able to comply with the need for contraception (abstinence, condom, birth control pill, or other acceptable form of contraception) during the entire study period
  • Diagnosis of MDS (WHO) with bone marrow cellularity greater than 30%, with low or intermediate-1 risk by the International Prognostic Scoring System (IPSS) score, and requiring treatment (i.e. transfusion-dependent)

Exclusion Criteria:

  • Active and uncontrolled infection
  • HIV positive test
  • Pregnant or breast feeding
  • Active and uncontrolled medical illness (pulmonary, cardiac, neurological, or other) that in the opinion of treating physician would likely interfere with study treatment
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00806598

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Genzyme, a Sanofi Company
Investigators
Principal Investigator: Tapan M. Kadia, M.D. M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00806598     History of Changes
Other Study ID Numbers: 2005-0115
Study First Received: December 9, 2008
Results First Received: January 30, 2013
Last Updated: March 8, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Myelodysplastic Syndrome
Aplastic Anemia
Thymoglobulin
Cyclosporine
Methylprednisolone
G-CSF

Additional relevant MeSH terms:
Anemia
Anemia, Aplastic
Myelodysplastic Syndromes
Preleukemia
Hematologic Diseases
Bone Marrow Diseases
Precancerous Conditions
Neoplasms
Antilymphocyte Serum
Cyclosporins
Cyclosporine
Lenograstim
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on April 15, 2014