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Fludarabine, Bendamustine and Rituximab Conditioning for Patients With Lymphoid Malignancies

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; Lymphoma

Intervention: Bendamustine (Drug); Rituximab (Drug); Fludarabine (Drug); Stem Cell Transplant (SCT) (Procedure)

Phase: Phase 1

Status: Completed

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Issa F. Khouri, MD, BS, Principal Investigator, Affiliation: M.D. Anderson Cancer Center

Summary

The goal of this clinical research study is to learn if bendamustine, when given with a stem cell transplant and chemotherapy (fludarabine and rituximab), can help the transplanted stem cells start to grow and make new blood cells in patients with leukemia and lymphoma. The safety of this combination will also be studied.

Clinical Details

Official title: Fludarabine, Bendamustine and Rituximab (FBR) Non-myeloablative Allogeneic Conditioning for Patients With Lymphoid Malignancies

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 Bendamustine

Detailed description: The Study Drugs: Rituximab is designed to attach to lymphoma cells, which may cause them to die. Fludarabine is designed to make cancer cells less able to repair damaged DNA. This may increase the likelihood of the cells dying. Bendamustine is designed to damage and destroy the DNA (genetic material) of cancer cells. Study Drug Administration and Stem Cell Transplant: If you are found to be eligible to take part in this study, you will be assigned to a dose level of bendamustine based on when you joined this study. 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 for up to 4 dose levels, until the highest tolerable dose of bendamustine is found. You will begin receiving the study drugs within 30 days after the screening visit. All of the study drugs will be given through a central venous catheter (CVC) that will be left in place the entire time that you are receiving study drugs. A CVC is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form for this procedure.

On Day - 13 (13 days before you receive the stem cell transplant) and then 1 time each week

for 4 weeks, you will receive rituximab over 5-7 hours through the CVC. If you have T-cell lymphoma, you will not receive rituximab.

On Days - 5 to -3, you will receive fludarabine and bendamustine over 1 hour each day through

the CVC. During this time, you will also receive hydrocortisone and tacrolimus through the CVC to help prevent or ease side effects (such as chills, rash, and/or hives).

On Day - 2, you will start to receive tacrolimus by CVC to help prevent graft-versus-host

disease. This will be changed to a dose of tacrolimus by mouth, once you are discharged from the hospital. You will continue to take tacrolimus by mouth for 6-8 months following your transplant.

On Days - 2 and -1, if your stems cells are from a matched unrelated donor, you will receive

thymoglobulin. On Day 0, you will receive the donor blood stem cells through the CVC over 30-45 minutes. On Days 1, 3, and 6 (after the stem cell transplant), you will receive methotrexate over 30 minutes each day through the CVC to help prevent graft-versus-host-disease. Patients receiving a matched unrelated donor will also be given methotrexate on day 11 after the transplant. Beginning on Day 7, you will receive filgrastim (G-CSF) through a needle under your skin 1 time each day until your white blood cell counts recover. Study Visits: You must stay in the Houston area for about 100 days after the stem cell transplant. You will be in the hospital for up to about 3-4 weeks after you receive the stem cell transplant. During this time, the following tests and procedures will be performed:

- Blood (about 3 teaspoons) will be collected for routine tests 1 time each day.

- When your doctor thinks it is needed, you will have imaging scans (such as the ones

performed during the screening visit) to check the status of the disease and/or for possible infections.

- When your doctor thinks it is needed, you will have transfusions of blood and/or

platelets.

- When your doctor thinks it is needed, you will have a bone marrow biopsy to check the

status of the disease. Between Days 25 and 35 after the stem cell transplant, the following tests and procedures will be performed:

- You will have CT scans to check the status of the disease.

- Blood (about 6 teaspoons) will be drawn for routine tests.

- You will have a bone marrow biopsy/aspirate to check the status of the disease.

- If your doctor thinks it is needed, you will have a PET scan to check the status of the

disease. Long-Term Follow-Up: Every 3 months after the stem cell transplant during the first year and then every 6 months for up to 3 years, the following tests and procedures will be performed:

- You will have CT scans to check the status of the disease.

- Blood (about 6 teaspoons) will be drawn for routine tests.

- You will have a bone marrow biopsy/aspirate to check the status of the disease.

- If your doctor thinks it is needed, you will have a PET scan to check the status of the

disease. Length of Study: You will be on study for up to about 3 years. You will be taken off study if the disease gets worse or you experience any intolerable side effects. End-of-Study Visit: After you are off study, you will have an end-of-study visit. At this visit, the following tests and procedures will be performed:

- You will have CT scans to check the status of the disease.

- Blood (about 6 teaspoons) will be drawn for routine tests.

- You will have a bone marrow biopsy/aspirate to check the status of the disease.

- If your doctor thinks it is needed, you will have a PET scan to check the status of the

disease. This is an investigational study. Rituximab and fludarabine are FDA approved and commercially available for the treatment of lymphoma. Fludarabine and bendamustine are FDA approved and commercially available for the treatment of chronic lymphocytic leukemia (CLL) . The use of bendamustine in combination with the other study drugs and a stem cell transplant for the treatment of lymphoma and leukemia is investigational. Up to 60 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. 18 to 70 years of age. 2. Patients with cluster of differentiation antigen 20 (CD20) + CLL, marginal zone, mantle cell and follicular lymphoma or T-cell lymphoid malignancies who are eligible for allogeneic transplantation. 3. Patients with relapsed diffuse large B-cell lymphoma may be included if there were not eligible for autologous transplantation. 4. A fully-matched sibling donor or matched unrelated donor. 5. Left ventricular EF > 40% with no uncontrolled arrythmias or symptomatic heart disease. 6. Forced expiratory volume at one second (FEV1), forced vital capacity (FVC) and diffusing capacity of lung for carbon monoxide (DLCO) > 40%. 7. Serum creatinine < 1. 6 mg/dL. Serum bilirubin < 3X upper limit of normal. 8. Serum glutamate pyruvate transaminase (SGPT) < 3X upper limit of normal. 9. Voluntary signed, written Institutional Review Board (IRB)-approved informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care. 10. 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 central nervous system (CNS) disease. 2. Pregnant (Positive Beta human chorionic gonadotropin (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. Patients with other malignancies diagnosed within 2 years prior to Study Day-13 (except skin squamous or basal cell carcinoma). 5. Active uncontrolled bacterial, viral or fungal infections. 6. History of Stroke within 6 months. 7. Myocardial infarction within the past 6 months prior to Study Day 1, or has New York Heart Association (NYHA) Class III or IV heart failure or arrythmias, unstable angina, uncontrolled congestive heart failure or arrythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening must be documented by investigator as not medically relevant. 8. A prior allogeneic transplant. 9. Serious medical or psychiatric illness likely to interfere with participation in this clinical study. 10. Patient has received other investigational drugs within 3 weeks before enrollment. 11. Hypersensitivity to bendamustine. 12. Prior known refractoriness to bendamustine.

Locations and Contacts

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

University of Texas MD Anderson Cancer Center Website

Starting date: February 2009
Last updated: October 16, 2014

Page last updated: August 23, 2015

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