Methylprednisolone, Horse Anti-Thymocyte Globulin, Cyclosporine, Filgrastim, and/or Pegfilgrastim or Pegfilgrastim Biosimilar in Treating Patients With Aplastic Anemia or Low or Intermediate-Risk Myelodysplastic Syndrome

Study Overview
=================
Brief Summary
-----------------
This phase II trial studies methylprednisolone, horse anti-thymocyte globulin, cyclosporine, filgrastim, and/or pegfilgrastim or pegfilgrastim biosimilar in treating patients with aplastic anemia or low or intermediate-risk myelodysplastic syndrome. Horse anti-thymocyte globulin is made from horse blood and targets immune cells known as T-lymphocytes. Since T-lymphocytes are believed to be involved in causing low blood counts in aplastic anemia and in some cases of myelodysplastic syndromes, killing these cells may help treat the disease. Methylprednisolone and cyclosporine work to suppress immune cells called lymphocytes. This may help to improve low blood counts in aplastic anemia and myelodysplastic syndromes. Filgrastim and pegfilgrastim are designed to cause white blood cells to grow. This may help to fight infections and help improve the white blood cell count. Giving methylprednisolone and horse anti-thymocyte globulin together with cyclosporine, filgrastim, and/or pegfilgrastim may be an effective treatment for patients with aplastic anemia or myelodysplastic syndrome.

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. To evaluate the efficacy of the combination of hATG (horse anti-thymocyte globulin), methylprednisolone, cyclosporine, and GCSF (filgrastim) in achieving response (complete response [CR], partial response [PR], or hematologic improvement [HI]) in patients with aplastic anemia, or myelodysplastic syndromes (MDS). SECONDARY OBJECTIVES: I. To assess the safety, tolerability, and toxicities of the combination of hATG, methylprednisolone, cyclosporine, and GCSF in patients with aplastic anemia, or MDS. II. To assess time to response, response duration, and overall survival of patients with aplastic anemia, or MDS being treated with the combination of hATG, methylprednisolone, cyclosporine, and GCSF. OUTLINE: Patients receive methylprednisolone intravenously (IV) over 10 minutes on days 1-4 and IV or orally (PO) with taper over days 5-30. Patients also receive horse anti-thymocyte globulin IV over 8 hours daily on days 1-4, cyclosporine PO twice daily (BID) on days 1-180, and pegfilgrastim or pegfilgrastim biosimilar subcutaneously (SC) on day 5 and/or filgrastim SC beginning on day 5 and continuing until absolute neutrophil count recovers. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6-12 months.

Official Title
-----------------
Phase II Study of Horse Anti-Thymocyte Globulin (hATG), Cyclosporine, Methylprednisolone, and GCSF (Filgrastim or Pegfilgrastim) in Patients With Aplastic Anemia (AA), or Low/Int-1 Risk Myelodysplastic Syndrome (MDS)

Conditions
-----------------
Aplastic Anemia, de Novo Myelodysplastic Syndrome, Myelodysplastic Syndrome, Previously Treated Myelodysplastic Syndrome

Intervention / Treatment
-----------------
* Biological: Anti-Thymocyte Globulin
* Drug: Cyclosporine
* Biological: Filgrastim
* Drug: Methylprednisolone
* Biological: Pegfilgrastim


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with the diagnosis of MDS (low, int-1 by International Prognostic Scoring System [IPSS], or hypocellular) who are either previously treated or untreated are eligible for this trial Patients with the diagnosis of aplastic anemia who are either previously treated or untreated are eligible if they are not currently candidates for an allogeneic stem cell transplant Patients must have been off of cytotoxic, immunosuppressive (except steroids), or targeted therapy for at least 2 weeks prior to entering this study, and have recovered from the toxic effects of that therapy to grade 1 or less Bilirubin < 2 mg/dL Aspartate aminotransferase (AST) < 3 x upper limit of normal (ULN) Creatinine < 2.5 x ULN Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial Patient must have the ability to understand the requirements of the study and signed informed consent; a signed informed consent by the patient or his legally authorized representative is required prior to their enrollment on the protocol Patients should have an indication for therapy for their disease such as transfusion dependence or morbidity associated with their cytopenia(s) such as bleeding, severe fatigue, or frequent/multiple infections (e.g. neutropenia) Exclusion Criteria: Pregnant women are excluded from this study; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the study agents, breastfeeding should be discontinued if the mother is treated on this study Known human immunodeficiency virus (HIV) infection Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Patient with documented hypersensitivity to any of the component medications
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (methylprednisolone, hATG, cyclosporine, G-CSF)<br>Patients receive methylprednisolone IV over 10 minutes on days 1-4 and IV or PO with taper over days 5-30. Patients also receive horse anti-thymocyte globulin IV over 8 hours daily on days 1-4, cyclosporine PO BID on days 1-180, and pegfilgrastim or pegfilgrastim biosimilar SC on day 5 and/or filgrastim SC beginning on day 5 and continuing until absolute neutrophil count recovers. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity. | Biological: Anti-Thymocyte Globulin<br>* Given IV<br>* Other names: Thymoglobulin;Drug: Cyclosporine<br>* Given PO<br>* Other names: SangCya;Biological: Filgrastim<br>* Given SC<br>* Other names: Tevagrastim;Drug: Methylprednisolone<br>* Given IV or PO<br>* Other names: Wyacort;Biological: Pegfilgrastim<br>* Given SC<br>* Other names: SD-01 sustained duration G-CSF;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Achievement of response | Measured by complete response (CR), partial response, or hematologic improvement. | Up to 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to response | Estimated according to the Kaplan-Meier method. | The interval between treatment start and the date of response, assessed up to 6 years | 
| Duration of CR | Estimated according to the Kaplan-Meier method. | Time interval between the date of CR to the date of first evidence of disease recurrence or death, assessed up to 6 years | 
| Overall survival | Estimated according to the Kaplan-Meier method. | Time from treatment start until the death or last follow-up time, assessed up to 6 years | 
| Incidence of adverse events | Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Tabulated by grade and course of therapy. Numbers of required dose reductions will be included in the toxicity report. | Up to 6 years |