Horse ATG in Patients With AA or Low/Int-1 Risk MDS - Full Text View

Purpose

The goal of this clinical research study is to learn if horse anti-thymocyte globulin (hATG), given in combination with methylprednisolone, cyclosporine, and G-CSF (filgrastim or pegfilgrastim), can help to control MM and/or low-int-1 risk MDS. The safety of this drug combination will also be studied.

hATG 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 AA and in some cases of MDS, 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 AA and in some cases of MDS.

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.

Condition	Intervention	Phase
Leukemia	Drug: hATG Drug: Cyclosporine Drug: Methylprednisone Drug: Pegfilgrastim Drug: Filgrastim	Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase II Study of Horse Anti-Thymocyte Globulin (hATG), Cyclosporine, Methylprednisone, and GCSF (Filgrastim or Pegfilgrastim) in Patients With Aplastic Anemia (AA), or Low/Int-1 Risk Myelodysplastic Syndrome (MDS)

Resource links provided by NLM:

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

Achievement of Response [ Time Frame: 3 months ] [ Designated as safety issue: No ]
Achievement of response defined: In aplastic anemia (AA) patients, response rate measured by complete response (CR) or partial response (PR); in myelodysplastic syndrome (MDS) patients, the response rate is measured by CR, PR, or hematologic improvement (HI). Criteria for HI per the Modified International Working Group Response Criteria in MDS. Patients eligible for trial and receive any dose of hATG and cyclosporine, included in estimating response rates and counted as treatment failures if response cannot be assessed for any reason.

Secondary Outcome Measures:

Time to Response [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
Time to response, duration of CR, and overall survival estimated according to Kaplan-Meier. Time to response defined as interval between treatment start and date of response. Duration of CR defined as time interval between date of CR and date of first evidence of disease recurrence or death, within patients who achieved CR. Patients alive and recurrence-free at last follow-up censored at that time. Overall survival defined as time from treatment start until death or last follow-up time. Toxicity summarized according to standard CTC criteria.

Estimated Enrollment:	100
Study Start Date:	June 2012
Estimated Primary Completion Date:	June 2018 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: hATG + Cyclosporine + Methylprednisone + GCSF hATG (ATGAM) 40 mg/kg/d by vein over 8 hours daily on days 1 - 4. Methylprednisone 1 mg/kg/day by vein daily for 4 days, on days 1 - 4, to be given prior to the hATG infusion each day. Cyclosporine 5 mg/kg by mouth daily given in 2 divided doses starting on day 1 and given for 6 months (180 days). G-CSF starting on day 5, administered as: Pegfilgrastim 6 mg subcutaneously (SQ) one time on day 5 and/or Filgrastim 300-480 mcg SQ starting on day 5 as needed to keep ANC >/= 1.5.	Drug: hATG 40 mg/kg by vein on Days 1 - 4. 35 mg/kg by vein on Days 1 - 4 (in patients with MDS age >/= 55). Other Names: Horse Anti-Thymocyte Globulin ATG Antithymocyte Globulin Thymoglobulin Drug: Cyclosporine 5 mg/kg by mouth daily given in 2 divided doses starting on Day 1 and given for 6 months (180 days). Other Names: Sandimmune CYA Cyclosporin A Drug: Methylprednisone 1 mg/kg by vein daily for 4 days on Days 1 - 4, to be given prior to the hATG infusion. Other Names: Methylprednisolone Depo-Medrol Medrol Solu-Medrol Drug: Pegfilgrastim 6 mg subcutaneously one time on Day 5 as needed to keep ANC >/= 1.5. Other Names: Neulasta PEG=G-CSF Drug: Filgrastim 300-480 mcg subcutaneously on Day 5 as needed to keep ANC >/= 1.5. Other Names: G-CSF Neupogen

Arms

Assigned Interventions

Experimental: hATG + Cyclosporine + Methylprednisone + GCSF

hATG (ATGAM) 40 mg/kg/d by vein over 8 hours daily on days 1 - 4. Methylprednisone 1 mg/kg/day by vein daily for 4 days, on days 1 - 4, to be given prior to the hATG infusion each day.

Cyclosporine 5 mg/kg by mouth daily given in 2 divided doses starting on day 1 and given for 6 months (180 days).

G-CSF starting on day 5, administered as:

Pegfilgrastim 6 mg subcutaneously (SQ) one time on day 5 and/or Filgrastim 300-480 mcg SQ starting on day 5 as needed to keep ANC >/= 1.5.

Drug: hATG

40 mg/kg by vein on Days 1 - 4.

35 mg/kg by vein on Days 1 - 4 (in patients with MDS age >/= 55).

Other Names:

Horse Anti-Thymocyte Globulin
ATG
Antithymocyte Globulin
Thymoglobulin

Drug: Cyclosporine

5 mg/kg by mouth daily given in 2 divided doses starting on Day 1 and given for 6 months (180 days).

Other Names:

Sandimmune
CYA
Cyclosporin A

Drug: Methylprednisone

1 mg/kg by vein daily for 4 days on Days 1 - 4, to be given prior to the hATG infusion.

Other Names:

Methylprednisolone
Depo-Medrol
Medrol
Solu-Medrol

Drug: Pegfilgrastim

6 mg subcutaneously one time on Day 5 as needed to keep ANC >/= 1.5.

Other Names:

Neulasta
PEG=G-CSF

Drug: Filgrastim

300-480 mcg subcutaneously on Day 5 as needed to keep ANC >/= 1.5.

Other Names:

G-CSF
Neupogen

Show Detailed Description

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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.
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.
All ages are eligible.
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.
Adequate organ function as defined as: liver function (bilirubin < 2mg/dL, AST and/or ALT <3 x ULN), kidney function (creatinine < 2.5 x ULN ).
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 (eg. 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 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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01624805

Contacts

Contact: Tapan Kadia, MD

713-563-3534

Locations

United States, Texas
UT MD Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Investigators

Principal Investigator:

Tapan Kadia, MD

UT MD Anderson Cancer Center

More Information

Additional Information:

UT MD Anderson Cancer Center Website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT01624805 History of Changes
Other Study ID Numbers:	2012-0334
Study First Received:	June 19, 2012
Last Updated:	April 5, 2013
Health Authority:	United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:

Leukemia
Aplastic Anemia
AA
Low/Int-1 Risk Myelodysplastic Syndrome
MDS
hATG
Horse Antithymocyte Globulin
ATG
Antithymocyte Globulin
Thymoglobulin
Cyclosporine
Sandimmune
CYA

Cyclosporin A
Methylprednisone
Methylprednisolone
Depo-Medrol
Medrol
Solu-Medrol
pegfilgrastim
Neulasta
PEG-G-CSF
Filgrastim
C-CSF
Neupogen

Additional relevant MeSH terms:

Anemia, Aplastic
Leukemia
Myelodysplastic Syndromes
Preleukemia
Anemia
Hematologic Diseases
Bone Marrow Diseases
Neoplasms by Histologic Type
Neoplasms
Precancerous Conditions
Antilymphocyte Serum
Cyclosporins
Cyclosporine
Lenograstim
Methylprednisolone acetate

Prednisolone acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 21, 2013