Clinical trial NCT00523809
Conditions: Breast Cancer Ovarian Cancer
Keywords: Breast Cancer Ovarian Cancer Stem Cell Transplantation Bevacizumab Fludarabine Melphalan Avastin Thymoglobulin ATG Antithymocyte Globulin Allogeneic Hematopoietic Stem Cell Transplantation AHSCT
Sponsor: M.D. Anderson Cancer Center
Start date: 2007-08-01; Completion date: 2011-10-01
Enrollment: 5 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The goal of this clinical research study is to learn if giving Avastin (bevacizumab) with standard chemotherapy and a blood stem cell transplant, in patients with an advanced solid tumor, can help to shrink the tumor or slow its growth. The safety of this treatment will also be studied.

Detailed description:
The Study Drugs:

Bevacizumab is designed to prevent or slow down the growth of cancer cells by blocking the growth of blood vessels.

The combination of standard chemotherapy drugs (fludarabine and melphalan) used for this study may help to improve the chances of your body accepting the stem cell transplant. Fludarabine is designed to make cancer cells less able to repair damaged DNA (the genetic material of cells) and weaken the immune system so that stem cells can stay in your body. Melphalan is designed to damage the cancer cells' DNA.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will have a central venous catheter inserted. A central venous catheter 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.

You will receive chemotherapy with bevacizumab, fludarabine, and melphalan in order to prepare for the stem cell transplant.

On Day 1, you will receive bevacizumab through a needle in your vein over 30 minutes.

On Days 2-6, you will receive fludarabine by vein over 30 minutes.

On Day 5-6, you will receive melphalan by vein over 30 minutes.

On Day 7, you will receive no study drugs.

Stem Cell Transplant and Post-Transplant Drug Administration:

On Day 8, you will have a stem cell transplant. Your study doctor will explain this procedure to you in more detail and you will sign a separate consent form.

After the transplant, you will receive the drugs tacrolimus and methotrexate. Tacrolimus and methotrexate are used to prevent graft versus host disease (GVHD), a condition that occurs when the transplanted cells attack the normal cells in the body.

Tacrolimus will be given by vein non-stop (24 hours a day) until you are able to take medications by mouth. Once you are able to take medications by mouth, your doctor will tell you how and when to take the oral medication. You will receive tacrolimus for 2-3 months. During the last month that tacrolimus is given, the dose will be lowered gradually.

Methotrexate will be given by vein over a few seconds on Days 9, 11, and 14. An additional dose of methotrexate will be given on Day 19 if your donor is your parent, child, or an unrelated family member.

If GVHD does occur, the GVHD will be treated with methylprednisolone by vein or by mouth, as needed. You may also be given steroid cream to use on the skin, if needed.

Starting at least 3 weeks after the transplant, as soon as your blood counts recover, you will receive bevacizumab every 2 weeks by vein over 30 minutes.

Post-Transplant Procedures:

You must stay in the hospital for about 3-4 weeks beginning on Day 1. While you are in the hospital, blood (about 2 teaspoons) will be drawn for routine tests every day.

You must stay in the Houston area for about 100 days after the transplant. Once a month during the 100 days after the transplant, and then every 3 months for the first year, you will have scans to check the status of the disease. The study doctor will decide which scans are necessary (chest x-rays, CT scans, and/or bone scans). You may also have a bone marrow aspirate and biopsy at these times. The bone marrow aspirate and biopsy would only be performed if your bone marrow was shown to be involved with the disease at the time of screening.

If the disease is still present at 2 months after the transplant, and you do not have GVHD, you will stop receiving tacrolimus within 2 weeks. After that, if the disease is still present after another 6 weeks, and you do not have GVHD, you may receive an infusion of donor lymphocytes (a type of white blood cell) by vein over about 30 minutes. This treatment with white blood cells may be repeated 2 more times with 6 weeks between each infusion.

Length of Study:

You will be taken off-study after 1 year.

Follow-Up Visits:

You will have follow-up visits as per standard of care.

This is an investigational study. The use of bevacizumab in transplant patients is not FDA approved. Melphalan and fludarabine are FDA approved and commercially available for transplant patients. Up to 18 patients will take part in this study. All will be enrolled at M. D. Anderson.

Arms: arm 1: Bevacizumab 10 mg/kg intravenous (IV) on Day 1; Fludarabine 25 mg/m\^2 IV Daily over 5 Days; Melphalan 70 mg/m\^2 IV Daily over 2 Days; Thymoglobulin 0.5 mg/kg IV on Day - 3, 1.5 mg/kg IV on Day - 2, and 2 mg/kg IV on Day -1; plus Allogeneic Hematopoietic Stem Cell Transplantation on Day 8.
Interventions: intervention 1: Bevacizumab intervention 2: Allogeneic Hematopoietic Stem Cell Transplantation intervention 3: Fludarabine intervention 4: Melphalan intervention 5: Thymoglobulin
Intervention descriptions: intervention 1: 10 mg/kg IV Daily Over 30 Minutes for 1 Day intervention 2: Stem Cell Transplantation on Day 8. intervention 3: 25 mg/m\^2 IV Daily Over 30 Minutes for 5 Days intervention 4: 70 mg/m\^2 IV Daily Over 30 Minutes for 2 Days intervention 5: 0.5 mg/kg IV on Day - 3, 1.5 mg/kg IV on Day - 2, and 2 mg/kg IV on Day -1.

Protocol documents: