Thymoglobulin and Cyclosporine in Patients With Aplastic Anemia or Myelodysplastic Syndrome

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Brief Title

Thymoglobulin and Cyclosporine in Patients With Aplastic Anemia or Myelodysplastic Syndrome

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

Brief Summary

      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.
    

Detailed Description

      Aplastic anemia is a condition that involves a low level of red blood cells (anemia), white
      blood cells, and platelets without evidence of another bone marrow disease. Anemia leads to
      fatigue, shortness of breath, and heart problems. Low platelet counts can lead to bruising
      and bleeding, and low white blood cell counts may cause an increased risk of infection,
      including pneumonia. Some of the treatment for AA includes transfusion, antibiotics and a
      combination of anti-thymocyte globulin (ATG) and cyclosporine with or without steroids, and
      growth factors such as G-CSF. For those who are eligible and have a donor, stem cell/bone
      marrow transplantation may be used.

      MDS is a bone marrow disorder that usually affects older adults. Treatment of the bone marrow
      failure that accompanies MDS is usually with supportive care with red blood cell and platelet
      transfusions, antibiotics, and combinations of hematopoietic growth factors, which may
      partially improve blood cell counts.

      It is often difficult to distinguish the hypoplastic variety of MDS from severe AA because
      both can result in bone marrow tests with very low cell count numbers. Earlier studies have
      shown that in some patients with the hypoplastic MDS, low blood counts respond to
      immunosuppressive treatment with ATG and cyclosporine. ATG is made from horse plasma.
      Thymoglobulin is a type of ATG made from rabbit plasma. Thymoglobulin has been successfully
      used to treat patients with AA who were previously treated with horse ATG but whose disease
      has returned. G-CSF is a growth factor that helps raise the white cell count after receiving
      chemotherapy. Methylprednisolone is a steroid that is commonly used in treating a number of
      medical conditions associated with people's abnormal immune response against themselves.

      If you are found to be eligible to take part in this study, you will receive a combination of
      thymoglobulin, cyclosporine, G-CSF, and methylprednisolone. Treatment will be with
      thymoglobulin, which will be dosed depending on your age and weight. It will be given by vein
      over several hours once a day for a total of 5 days. You will receive the steroid
      methylprednisolone by vein before each dose of thymoglobulin to decrease the risk of
      developing allergic reactions to thymoglobulin. After 5 days of receiving methylprednisolone
      by vein, you will start taking it by mouth once a day at a decreasing dose over about 3
      weeks.

      The first 5 days of treatment will be given at M. D. Anderson but you will treated outside
      the hospital for the rest of the time unless complications develop.

      You will be started on cyclosporine as well as G-CSF after completion of thymoglobulin. You
      will take cyclosporine by mouth twice a day for 6 months. Your physician may continue
      cyclosporine longer at his discretion. You will receive G-CSF as an injection under the skin
      for 3 months (or longer) once a day at the discretion of the treating physician starting at
      the same time as cyclosporine is started.

      You will also receive antibiotic pills to help decrease the risk of infection. You will take
      levofloxacin, valacyclovir, fluconazole, or a similar antibiotic by mouth every day for the
      length of the study or until your treating physician finds appropriate.

      If you have a history of heart disease and you take aspirin for this, your treating physician
      may consider stopping the aspirin because of your low platelet count as a result of your
      disease. This may increase your risk of heart attacks.

      You will have blood tests (about 2 tablespoons each) once or twice a week for the first month
      and then once every 2-4 weeks until the end of the study to check if your blood counts are
      improving. The level of cyclosporine in your blood will also be checked at these times. It
      will require about 1 tablespoon for each of these tests. Monitoring of cyclosporine levels is
      a routine test done on all patients who receive this drug in order to avoid toxic blood
      levels and side effects.

      At about 3 months, you will have a repeat bone marrow biopsy and aspiration as well as blood
      tests (about 3 tablespoons) to evaluate your response to the treatment.

      You will continue cyclosporine for about 6 months (or longer if your doctor feels that it is
      in your interest) and will receive G-CSF for up to about 3 months (or longer if in your
      interest). If you develop serious side effects or if the disease gets worse at any time you
      will be taken off the study.

      At the time when your doctor feels you have had the best possible response to the treatment
      and you are coming off study, blood tests (about 3 tablespoons) will be repeated.

      Your doctor will continue to remain in touch with you to ensure that your disease remains
      under control. This may be done by arranging follow-up visits or through phone or other means
      of communication.

      This is an investigational study. All the drugs used in this study are FDA approved and
      commercially available. Their use together in this study is experimental. A total of 60
      patients will take part in this study. All will be enrolled at M. D. Anderson.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Overall Response


Condition

Myelodysplastic Syndrome

Intervention

Thymoglobulin

Study Arms / Comparison Groups

 Thymoglobulin + Cyclosporin
Description:  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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

53

Start Date

May 2005

Completion Date

June 2012

Primary Completion Date

June 2012

Eligibility 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
      

Gender

All

Ages

15 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Tapan M. Kadia, M.D., , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00806598

Organization ID

2005-0115


Responsible Party

Sponsor

Study Sponsor

M.D. Anderson Cancer Center

Collaborators

 Genzyme, a Sanofi Company

Study Sponsor

Tapan M. Kadia, M.D., Principal Investigator, M.D. Anderson Cancer Center


Verification Date

March 2013