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

M.D. Anderson Cancer Center

Status and phase: Enrolling; Phase 2

Conditions: Previously Treated Myelodysplastic Syndrome; de Novo Myelodysplastic Syndrome; Myelodysplastic Syndrome; Aplastic Anemia

Treatments: Biological: Pegfilgrastim; Biological: Filgrastim; Drug: Methylprednisolone; Biological: Anti-Thymocyte Globulin; Drug: Cyclosporine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01624805

2012-0334 (Other Identifier)

NCI-2012-01096 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 140 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients with the diagnosis of MDS (Low, Int-1 by IPSS, or hypocellular) who are either previously treated or untreated are eligible for this trial.

2. 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.

3. Patients ages 18 years and older are eligible

4. 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.

5. Adequate organ function as defined below:

   • liver function (bilirubin < 2mg/dL, AST <3 x ULN)
   • kidney function (creatinine < 2.5 x ULN ).

6. ECOG performance status of ≤ 2.

7. 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.

8. A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.

9. 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.

10. 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 (eg. neutropenia).

Exclusion criteria

1. 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.
2. Known HIV infection.
3. 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.
4. Patient with documented hypersensitivity to any of the component medications.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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140 participants in 1 patient group

Treatment (methylprednisolone, hATG, cyclosporine, G-CSF)

Experimental group

Description:

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.

Treatment:

Drug: Cyclosporine

Biological: Anti-Thymocyte Globulin

Drug: Methylprednisolone

Biological: Filgrastim

Biological: Pegfilgrastim