Clinical trial NCT01191749: Alemtuzumab in Myelodysplastic Syndrome (MDS), Aplastic Anemia, and T-Cell Large Granular Lymphocytic Leukemia (T-GL)
Official title: Phase II Pilot Study Of Alemtuzumab In Patients With Low Or INT-1 Risk Myelodysplastic Syndrome (MDS), Aplastic Anemia (AA), Or T-Cell Large Granular Lymphocytic Leukemia (T-LGL)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Leukemia
Keywords: Hematologic Disorder
Aplastic Anemia
T - Cell Large Granular Lymphocytic Leukemia
T-LGL
Myelodysplastic Syndrome
Chronic Lymphocytic Leukemia
CLL
Chemotherapy
Alemtuzumab
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
First posted: 2010-08-31
Enrollment: 7
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this clinical research study is to determine the effectiveness of alemtuzumab in patients with aplastic anemia, MDS, or T-Cell large granular lymphocytic leukemia. The safety of alemtuzumab will also be studied.

Detailed description: The Study Drug:

Alemtuzumab is designed to attach to a protein that is found on certain immune cells, which may cause the cell to die.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive alemtuzumab on Days 1-10 of one 28-day cycle. It will be given either by vein over 2 hours or by injection under the skin 1 time a day. Your doctor will tell you how the drug will be given.

In order to get alemtuzumab provided for your treatment, the study staff will be filling out a form with your name and medical information (protected health information) for the company as part of the Campath Distribution Program.

All participants will receive the same dose of alemtuzumab unless the starting dose causes intolerable side effects. If this happens, all future participants will receive a lower dose.

Depending on your doctor's decision, to lower the risk of side effects you will receive Tylenol (acetaminophen) and Benadryl (diphenhydramine) or other drugs such as steroids (either by mouth or by a short infusion by vein), 30 minutes before each alemtuzumab dose.

If you are receiving alemtuzumab and have chills during the infusion, you may receive Demerol (meperidine hydrochloride, a painkiller) to help control them.

Starting on Day 1 and continuing at least 8 weeks after the last dose of study drug, you will be given 2 antibiotics to help fight infection. You will take Valacyclovir (or a similar drug) 1 time each day. You will take Trimethoprim/Sulfamethoxazole (or a similar drug) 2 times a day, 3 times per week. You will take both antibiotics by mouth.

Study Visits:

At Week 1:

* You will have a physical exam, including measurement of your weight and vital signs.
* Your performance status will be recorded.
* Blood (about 1 tablespoon) will be drawn for routine tests.

At Weeks 2-4, blood (about 1 tablespoon) will be drawn for routine tests.

Beginning at Week 5 (+/- 3 days) and then 1 time monthly:

* You will have a physical exam, including measurement of your weight and vital signs.
* Your performance status will be recorded.
* Blood (about 1 tablespoon) will be drawn for routine tests.

At Week 12 (+/- 3 days) (end of the 3rd month), you will have a bone marrow aspiration and/or biopsy to test for chromosome abnormalities (if chromosomes were abnormal at screening) and to check the status of the disease. You may have additional bone marrow aspirations or biopsies if your doctor feels they are necessary.

You will be asked about any side effects you may be having at each of your study visits. At any time during the study, if the doctor thinks it is needed, you will have a chest x-ray, a CT scan, or a PET scan to check the status of the disease.

Length of Study:

You will receive only one cycle of the study drug. Your participation on the study will be over after you have completed the end-of-study visit. You will be taken off study early if the disease gets worse or intolerable side effects occur.

End-of Study-Visit:

When you come off study you will have an end-of-study visit. At this visit, the following tests and procedures will be performed:

* Blood (about 2 tablespoons) will be drawn for routine tests.
* You will have a physical exam, including measurement of your vital signs.
* Your performance status will be recorded.
* You will have a bone marrow aspiration and/or biopsy to check for chromosome abnormalities, test for low levels of leukemia or lymphoma, to check the status of the disease, and molecular testing. Molecular tests are designed to look at the way the different parts of a cell (including DNA, RNA, and proteins) work together.
* Blood (about 2 teaspoons) will be drawn to check levels of T-cells and immunoglobulins.

This is an investigational study. Alemtuzumab is FDA-approved for the treatment of some patients with B-cell chronic lymphocytic leukemia (CLL). The use of alemtuzumab to treat MDS, aplastic anemia, or T-cell large granular lymphocytic leukemia is investigational.

Up to 29 participants will take part in this study. All participants will be enrolled at MD Anderson.

Eligibility criteria: Inclusion Criteria:

1. Patients with the diagnosis of MDS (Low, Int-1 by IPSS, or hypocellular) who are either previously untreated or who have been previously treated are eligible for this trial.
2. Patients with the diagnosis of aplastic anemia who have or have not been previously treated are eligible for inclusion if they are not currently candidates for an allogeneic stem cell transplant.
3. Patients with the diagnosis of T-LGL who have or have not been previously treated are eligible for inclusion.
4. Patients must have been off of cytotoxic, immunosuppressive, or targeted therapy (except hydroxyurea) 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: liver function (bilirubin \< or = 2mg/dL, AST and/or ALT \< or = 3 x ULN) ; kidney function (creatinine \< or = 2.5 x ULN ).
6. ECOG performance status of \< or = 3.
7. The effects of alemtuzumab on the developing human fetus are unknown. For this reason, 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 alemtuzumab is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with alemtuzumab, breastfeeding should be discontinued if the mother is treated with alemtuzumab. These potential risks may also apply to other agents used in this study.
2. Known HIV infection.
3. Known Hepatitis B or Hepatitis C infection.
4. 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.
5. Patient with documented hypersensitivity to alemtuzumab.

Primary outcomes:
measure: Overall Response - Number of Participants Who Achieved Complete Remission (CR)+Partial Remission (PR) - as Per International Working Group (IWG) Response Criteria
timeFrame: Up to 6 months following treatment; response assessed every 2 months
Secondary outcomes:
Other outcomes:
Locations:
city: Houston
country: United States
facility: UT MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: UT MD Anderson Cancer Center
name: Tapan Kadia, MD
role: PRINCIPAL_INVESTIGATOR
References: