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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

Primary Purpose

Aplastic Anemia, de Novo Myelodysplastic Syndrome, Myelodysplastic Syndrome

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Anti-Thymocyte Globulin

Cyclosporine

Filgrastim

Methylprednisolone

Pegfilgrastim

About this trial

This is an interventional treatment trial for Aplastic Anemia

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

M D Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

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

Arm 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.

Outcomes

Primary Outcome Measures

Achievement of response

Measured by complete response (CR), partial response, or hematologic improvement.

Secondary Outcome Measures

Time to response

Estimated according to the Kaplan-Meier method.

Duration of CR

Estimated according to the Kaplan-Meier method.

Overall survival

Estimated according to the Kaplan-Meier method.

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.

Full Information

NCT ID

NCT01624805

First Posted

June 19, 2012

Last Updated

June 20, 2023

Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT01624805

Brief Title

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

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)

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Recruiting

Study Start Date

June 25, 2012 (Actual)

Primary Completion Date

June 30, 2025 (Anticipated)

Study Completion Date

June 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Anti-Thymocyte Globulin

Other Intervention Name(s)

Antithymocyte Globulin, Antithymocyte Serum, ATG, ATGAM, ATS, Thymoglobulin

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Cyclosporine

Other Intervention Name(s)

27-400, Ciclosporin, CsA, Cyclosporin, Cyclosporin A, Gengraf, Neoral, OL 27-400, Sandimmun, Sandimmune, SangCya

Intervention Description

Given PO

Intervention Type

Biological

Intervention Name(s)

Filgrastim

Other Intervention Name(s)

FILGRASTIM, LICENSE HOLDER UNSPECIFIED, G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, rG-CSF, Tevagrastim

Intervention Description

Given SC

Intervention Type

Drug

Intervention Name(s)

Methylprednisolone

Other Intervention Name(s)

Adlone, Caberdelta M, DepMedalone, Depo Moderin, Depo-Nisolone, Duralone, Emmetipi, Esametone, Firmacort, Medlone 21, Medrate, Medrol, Medrol Veriderm, Medrone, Mega-Star, Meprolone, Methylprednisolonum, Metilbetasone Solubile, Metrocort, Metypresol, Metysolon, Predni-M-Tablinen, Prednilen, Radilem, Sieropresol, Solpredone, Summicort, Urbason, Veriderm Medrol, Wyacort

Intervention Description

Given IV or PO

Intervention Type

Biological

Intervention Name(s)

Pegfilgrastim

Other Intervention Name(s)

Filgrastim SD-01, filgrastim-SD/01, Fulphila, HSP-130, Jinyouli, Neulasta, Neulastim, Pegfilgrastim Biosimilar HSP-130, SD-01, SD-01 sustained duration G-CSF

Intervention Description

Given SC

Primary Outcome Measure Information:

Title

Achievement of response

Description

Measured by complete response (CR), partial response, or hematologic improvement.

Time Frame

Up to 6 years

Secondary Outcome Measure Information:

Title

Time to response

Description

Estimated according to the Kaplan-Meier method.

Time Frame

The interval between treatment start and the date of response, assessed up to 6 years

Title

Duration of CR

Description

Estimated according to the Kaplan-Meier method.

Time Frame

Time interval between the date of CR to the date of first evidence of disease recurrence or death, assessed up to 6 years

Title

Overall survival

Description

Estimated according to the Kaplan-Meier method.

Time Frame

Time from treatment start until the death or last follow-up time, assessed up to 6 years

Title

Incidence of adverse events

Description

Time Frame

Up to 6 years

10. Eligibility

Sex

All

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Tapan Kadia, MD

Phone

713-563-3534

tkadia@mdanderson.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Tapan M Kadia

Organizational Affiliation

M.D. Anderson Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

M D Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Tapan M. Kadia

Phone

713-563-3534

tkadia@mdanderson.org

First Name & Middle Initial & Last Name & Degree

Tapan M. Kadia

12. IPD Sharing Statement

Links:

URL

http://www.mdanderson.org

Description

MD Anderson Cancer Center

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