DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



Allogeneic Stem Cell Transplant for Chronic Lymphocytic Leukemia (CLL)

Information source: M.D. Anderson Cancer Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Leukemia

Intervention: Busulfan (Drug); Clofarabine (Drug); Gemcitabine (Drug); Thymoglobulin (Drug); Allogeneic Stem Cell Transplantation (Procedure); Filgrastim (Drug); Tacrolimus (Drug); Methotrexate (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Chitra M. Hosing, MD, Principal Investigator, Affiliation: M.D. Anderson Cancer Center

Overall contact:
Chitra M. Hosing, MD, Phone: 713-792-8750

Summary

The goal of this clinical research study is to learn the highest tolerable dose of gemcitabine (out of 4 possible doses) that can be given in combination with busulfan and clofarabine before an allogeneic stem cell transplant. Researchers also want to learn if this combination can help to control CLL. The safety of this treatment will also be studied. Busulfan is designed to bind to DNA (the genetic material of cells), which may cause cancer cells to die. It is commonly used in stem cell transplants. Clofarabine and gemcitabine are designed to block the growth of cancer cells, which may cause the cancer cells to die.

Clinical Details

Official title: Clofarabine, Gemcitabine and Busulfan Followed by Allogeneic Stem Cell Transplantation for Chronic Lymphocytic Leukemia (CLL)

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Maximum Tolerated Dose (MTD) of Gemcitabine with Busulfan and Clofarabine

Secondary outcome: Success Rate

Detailed description: Study Drug Administration:

On a day between Day - 15 and -8 (between 15 and 8 days before you receive the stem cell

transplant), you will receive a low-level "test" dose of busulfan by vein over about 1 hour.

You may receive the test dose before Day - 8 as an outpatient in the clinic, or on Day -8 as

an inpatient in the hospital. Blood (about 1 teaspoon each time) will then be drawn for pharmacokinetic (PK) testing up to 11 times over the 11 hours after the busulfan dose test dose. PK testing measures the amount of study drug in the body at different time points, and in this case will be used to figure out what your dose of busulfan should be. The study staff will tell you more about this PK testing schedule. The PK testing will help the doctor decide your dose of busulfan

for Days - 6 through -3.

A heparin lock line will be placed in your vein before the PK testing begins to lower the number of needle sticks needed for these draws. If for any reason it is not possible for the PK tests to be performed, you will receive the standard dose of busulfan.

On Day - 9 or Day -7, you will be admitted to the hospital and given fluids by vein to

hydrate you.

On Days - 6 and -4, you will receive gemcitabine by vein over 10-25 minutes. The dose you

receive will be based on when you join this study. Up to 4 dose levels of gemcitabine will be tested. Up to 3 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of gemcitabine is found. Once the highest dose is found, additional participants will be enrolled at that dose. The number of patients in this group will depend on how many have been enrolled in the other groups.

Each day on Days - 6 through Day -3, you will receive clofarabine by vein over 1 hour

followed by your body-specific dose of busulfan by vein over 3 hours. If for any reason you could not have the PK tests performed, you will receive the standard busulfan dose on these days.

On Day - 3 through Day -1, if your stem cell donor is not related to you, you will receive

antithymocyte globulin (ATG) by vein over 4 hours each day. ATG is designed to weaken your immune system in order to lower the risk that your body will reject the transplant.

Beginning on Day - 2, you will receive tacrolimus over 24 hours every day until you are able

to take it by mouth. Tacrolimus is designed to weaken the immune system and lower the risk

of graft-versus-host-disease (GVHD - a reaction of the donor's immune cells against your

body). Once you are able to take tacrolimus by mouth, you will take it every day for about 6 months, or until the doctor thinks it is safe to stop taking. On Day 0, you will receive the donor's stem cells by vein. The infusion will last anywhere from about 30 minutes to several hours. On Days 1, 3, 6, and 11, you will receive methotrexate by vein over about 15 minutes. Methotrexate is also designed to weaken the immune system and lower the risk of GVHD. Starting 1 week after the transplant, you will receive filgrastim (G-CSF) as an injection under the skin 1 time each day until your blood cell levels return to normal. You may be given other standard drugs to help decrease the risk of side effects. You may ask the study staff for information about how the drugs are given and their risks. Study Visits:

On a day between Day - 15 and Day -8, and then on Day -5 and Day -3 (before the busulfan test

dose, and then a day after the first and second dose of gemcitabine, for a total of 3 times), blood (about 2 teaspoons) will be drawn for tests to check the effect of the study drugs on the DNA (genetic material) of blood cells. About 4 weeks after the transplant:

- You will have a physical exam, including measurement of your vital signs (blood

pressure, temperature, heart rate, and breathing rate).

- You will be asked about how you are feeling and about any side effects you may be

having.

- You will be checked for possible reactions to the study treatment, including GVHD.

- Blood (about 4 tablespoons) will be drawn for routine tests, to see how the transplant

has taken, and to check the status of the disease. Length of Treatment: You will be on study for about 2 years. You will be taken off study early if you have graft failure (the transplant does not "take"), if the disease comes back and needs another treatment, if you cannot follow the study directions, if your study doctor think it is in your best interest, or if you want to leave the study. You must talk to the study doctor if you want to leave the study early. It may be life-threatening to leave the study after you have begun to receive the study drugs but before you receive the stem cells, because your blood cell counts will be dangerously low. Follow-Up: About 3, 6, and 12 months after the transplant, and then every 6 months for 1 more year:

- You will have a physical exam.

- You will be asked about how you are feeling and about any side effects you may be

having.

- You will be checked for possible reactions to your treatment, including GVHD.

- Blood (about 4 tablespoons) will be drawn for routine tests, to see how well the

transplant has taken, and to check the status of the disease.

- At any point that your doctor thinks they are needed, you will have a bone marrow

aspiration and computed tomography (CT) scans to check the status of the disease. To collect a bone marrow aspirate, an area of the hip or other site is numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large needle. The study staff will also stay in contact with your local doctor to find out if the disease comes back and to check how you are doing. This is an investigational study. Gemcitabine and clofarabine are FDA approved and commercially available for the treatment of leukemia. Busulfan is FDA approved and commercially available for use in stem cell transplantation. It is investigational to test for the best dose of gemcitabine that can be given with busulfan and clofarabine to help prevent the disease from coming back. Up to 30 patients will take part in this study. All will be enrolled at MD Anderson.

Eligibility

Minimum age: 18 Years. Maximum age: 70 Years. Gender(s): Both.

Criteria:

Inclusion Criteria: 1. Age 18 to 70 years of age. 2. Patients with chronic lymphocytic leukemia, prolymphocytic leukemia, or Richter's transformation who are eligible for allogeneic transplantation and are not eligible for protocols of higher priority. 3. A 10/10 HLA matched (high resolution typing at A, B, C, DRB1, DQ1) sibling or unrelated donor. 4. Left ventricular EF > 40%. 5. FEV1, FVC and corrected DLCO > 40%. 6. Serum creatinine < 1. 6 mg/dL. Serum bilirubin < 2X upper limit of normal. 7. SGPT < 2X upper limit of normal. 8. Voluntary signed, written IRB-approved informed consent. 9. Men and women of reproductive potential must agree to follow accepted birth control methods for the duration of the study. Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i. e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Male subject agrees to use an acceptable method for contraception for the duration of the study. Exclusion Criteria: 1. Patient with active CNS disease. 2. Pregnant (Positive Beta HCG test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization) or currently breast-feeding. Pregnancy testing is not required for post-menopausal or surgically sterilized women. 3. Known infection with HIV, HTLV-I, Hepatitis B, or Hepatitis C. 4. Active uncontrolled bacterial, viral or fungal infections. 5. Patient has received other investigational drugs within 2 weeks before enrollment.

Locations and Contacts

Chitra M. Hosing, MD, Phone: 713-792-8750

University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States; Recruiting
Additional Information

University of Texas MD Anderson Cancer Center Website

Starting date: November 2012
Last updated: June 11, 2015

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017