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Horse ATG in Patients With Aplastic Anemia (AA) or Low/Int-1 Risk Myelodysplastic Syndrome (MDS)

This study is currently recruiting participants.
Verified October 2017 by M.D. Anderson Cancer Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT01624805
First Posted: June 21, 2012
Last Update Posted: October 24, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
  Purpose

You are being asked to take part in this study because you have aplastic anemia (AA) or low/int-1 risk myelodysplastic syndrome (MDS).

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 AA 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.

This is an investigational study. hATG, cyclosporine, methylprednisolone, and filgrastim/pegfilgrastim are all FDA approved and commercially available for use in patients with AA and MDS. The use of filgrastim/pegfilgrastim with this drug combination is investigational.

Up to 100 patients will take part in this study. All will be enrolled at MD Anderson.


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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (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 ]
    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 ]
    Time to response defined as interval between treatment start and date of response. Time to response estimated according to Kaplan-Meier.


Estimated Enrollment: 100
Study Start Date: June 2012
Estimated Study Completion Date: June 2019
Estimated Primary Completion Date: June 2019 (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

Detailed Description:

Study Drug Administration:

If you are found to be eligible to take part in this study, you will be admitted to the hospital. On the first day, before starting the hATG, a small amount of diluted hATG will be injected under your skin to make sure that you are not allergic to it. If you have a reaction, more testing may be done. If the reaction is severe, you will be taken off study.

On Days 1-4 you will receive methylprednisolone by vein over about 10 minutes. You will receive hATG by vein over 8 hours.

If you are able to tolerate ATG without any significant side effects, you should be out of the hospital in about 4-5 days.

On Days 1-180 you will take cyclosporine by mouth 2 times a day at about the same time every day.

On Day 5 (or starting on Day 5) you will receive filgrastim or pegfilgrastim by an injection under your skin. Your doctor will decide which drug you will receive. If you receive pegfilgrastim, you will receive it one time on Day 5. If you receive filgrastim, you will receive it starting on Day 5. You will continue to receive it until your blood counts recover.

You will be given standard drugs to help decrease the risk of side effects. You may be given a drug called eltrombopag to help increase your platelet counts if you have low platelets or complications related to low platelets. You may ask the study staff for information about how the drugs are given and their risks.

Study Visits:

One time weekly for the first 4-6 weeks and then 1 time a month during Months 2-6

  • Your complete medical history will be recorded.
  • You will have a physical exam, including measurement of your height, weight, and vital signs (blood pressure, heart rate, breathing rate, and temperature).
  • Blood (about 2 tablespoons) will be drawn for routine tests.

At the end of Month 3 and then when the doctor thinks it is needed, you will have a bone marrow aspirate/biopsy to check the status of the disease.

Length of Treatment:

You may continue taking the study drug for up to 6 months. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over once you have completed the follow-up visits.

Follow-Up Visits:

When you are off treatment, every 6-12 months you will be called by a member of the study staff. You will be asked about any side effects you may be having. The phone calls will take about 5-10 minutes.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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. All ages 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 as: 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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01624805


Contacts
Contact: Tapan Kadia, MD 713-563-3534

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Tapan Kadia, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01624805     History of Changes
Other Study ID Numbers: 2012-0334
NCI-2012-01096 ( Registry Identifier: NCI CTRP )
First Submitted: June 19, 2012
First Posted: June 21, 2012
Last Update Posted: October 24, 2017
Last Verified: October 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

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
Myelodysplastic Syndromes
Preleukemia
Anemia, Aplastic
Hematologic Diseases
Bone Marrow Diseases
Precancerous Conditions
Neoplasms
Cyclosporins
Cyclosporine
Thymoglobulin
Antilymphocyte Serum
Lenograstim
Prednisolone acetate
Methylprednisolone acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Calcineurin Inhibitors