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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Previously Treated Myelodysplastic Syndrome; Myelodysplastic Syndrome; Aplastic Anemia; de Novo Myelodysplastic Syndrome
• Intervention / Treatment: Biological: Pegfilgrastim; Biological: Filgrastim; Biological: Anti-Thymocyte Globulin; Drug: Cyclosporine; Drug: Methylprednisolone

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.

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Tapan Kadia, MD; Phone Number: 713-563-3534; Email: tkadia@mdanderson.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • M D Anderson Cancer Center
      • Contact: Tapan M. Kadia; Phone Number: 713-563-3534; Email: tkadia@mdanderson.org
      • Principal Investigator: Tapan M. Kadia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (methylprednisolone, hATG, cyclosporine, G-CSF); 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: Pegfilgrastim; Given SC; Other Names: Filgrastim SD-01; filgrastim-SD/01; Fulphila; HSP-130; Jinyouli; Neulasta; Neulastim; Pegfilgrastim Biosimilar HSP-130; SD-01; SD-01 sustained duration G-CSF; Biological: Filgrastim; Given SC; Other Names: G-CSF; r-metHuG-CSF; Neupogen; Recombinant Methionyl Human Granulocyte Colony Stimulating Factor; rG-CSF; Tevagrastim; FILGRASTIM, LICENSE HOLDER UNSPECIFIED; Biological: Anti-Thymocyte Globulin; Given IV; Other Names: ATGAM; ATG; Antithymocyte Globulin; Antithymocyte Serum; ATS; Thymoglobulin; Drug: Cyclosporine; Given PO; Other Names: 27-400; Sandimmune; Ciclosporin; CsA; Neoral; Gengraf; Sandimmun; Cyclosporin; Cyclosporin A; OL 27-400; SangCya; Drug: Methylprednisolone; Given IV or PO; Other Names: Medrol; Wyacort; Adlone; Caberdelta M; DepMedalone; Depo Moderin; Depo-Nisolone; Duralone; Emmetipi; Esametone; Firmacort; Medlone 21; Medrate; Medrol Veriderm; Medrone; Mega-Star; Meprolone; Methylprednisolonum; Metilbetasone Solubile; Metrocort; Metypresol; Metysolon; Predni-M-Tablinen; Prednilen; Radilem; Sieropresol; Solpredone; Summicort; Urbason; Veriderm Medrol

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

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Tapan M Kadia, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• MD Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2012
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: June 19, 2012
• First Submitted That Met QC Criteria: June 20, 2012
• First Posted (Estimated): June 21, 2012

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 10, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Marrow Failure Disorders; Hematologic Diseases; Bone Marrow Diseases; Anemia; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Anemia, Aplastic; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Carbohydrates; Polycyclic Compounds; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Intercellular Signaling Peptides and Proteins; Pregnadienetriols; Glycoproteins; Glycoconjugates; Macrocyclic Compounds; Biological Products; Complex Mixtures; Peptides, Cyclic; Colony-Stimulating Factors; Hematopoietic Cell Growth Factors; Cytokines; Prednisolone; Immune Sera; Methylprednisolone; Cyclosporine; Cyclosporins; Antilymphocyte Serum; Granulocyte Colony-Stimulating Factor; Filgrastim; pegfilgrastim; thymoglobulin; exifone; Medrol Veriderm
• Other Study ID Numbers: 2012-0334 (Other Identifier: M D Anderson Cancer Center); NCI-2012-01096 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No