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Adaptive Randomization of Fludarabine-Melphalan Versus Fludarabine-Cyclophosphamide Conditioning Regimen in Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation Using HLA-Matched Related Donor for Metastatic Renal Cell Carcinoma


Phase 2
N/A
65 Years
Not Enrolling
Both
Renal Cell Cancer

Thank you

Trial Information

Adaptive Randomization of Fludarabine-Melphalan Versus Fludarabine-Cyclophosphamide Conditioning Regimen in Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation Using HLA-Matched Related Donor for Metastatic Renal Cell Carcinoma


Registration:

When you are willing to undergo stem cell transplantation for kidney cancer, have possible
related donors, and the study doctor decides you are eligible to participate, you will be
enrolled in this study.

Before treatment begins, you will have a complete physical exam, including blood (about 1-2
tablespoons) and urine tests. An electrocardiogram (ECG--a test to measure the electrical
function of the heart) and a heart scan will be done. A test of lung function will be done.
This will involve blowing into a machine that records your lung capacity. Tissue typing
will also be done by blood test on you and your possible donors to find out if you have a
donor or not. Women who are able to have children must have a negative blood test in order
to participate.

If you have a suitable related donor, have financial approval for the transplant procedure,
and are still eligible in this study, you will go for the stem cell transplantation. A
separate informed consent about the transplant procedure will be provided to you. You will
need to sign and agree with the second informed consent before the start of treatment. This
informed consent is only for you to be enrolled and registered in the study.

If you have no suitable related donor, no financial approval for the transplant procedure,
and/or you refuse to undergo transplant for non-medical reasons, you will not have a stem
cell transplant but will still remain in our study. You can receive any form of
non-transplant treatment from your physician. Study researchers will only follow your
progress, so that in the future, they can compare your progress with those who had the stem
cell transplant.

This is an investigational study. About 480 patients will take part in this study. All
patients will be enrolled at M. D. Anderson Cancer Center.

Treatment:

The two different chemotherapy regimens used in this study are fludarabine and melphalan, or
fludarabine and cyclophosphamide. They act by suppressing our immune system and make space
in our bone marrow so as to prepare for the new bone marrow to grow.

Before treatment starts, you will have a complete physical exam, including blood (about 1-2
tablespoons) and urine tests. An electrocardiogram (ECG-a test to measure the electrical
activity of the heart) and a heart scan will be done. A test of lung function will be done.
This will involve blowing into a machine that records your lung capacity. Tests will be
performed to look at the status of your cancer, including chest x-ray, bone scan, CT scans,
and MRI scan if needed. You will have a dental exam. Women who are able to bear children
must have a negative blood pregnancy test in order to participate.

In this study, you will receive high-dose chemotherapy to prepare for the blood stem cell
transplant. Two different types of chemotherapy will be used. You will be assigned to
receive one of the chemotherapy treatments. As the study moves forward, the group treatment
that is shown to be more effective will receive more new participants than the other one.
The first chemotherapy treatment is a combination of fludarabine and melphalan. The second
chemotherapy treatment is a combination of fludarabine and cyclophosphamide. The drug
fludarabine will be given through a needle in your vein on Days 1-5. Depending on which
treatment group you are assigned to, the drugs melphalan or cyclophosphamide will be given
through a needle in your vein on Days 4 and 5, along with your scheduled dose of
fludarabine. Day 6 will be a rest day; no drugs will be given. The stem cell transplant
will be performed on Day 7. Bone marrow from the donor may be used instead of blood stem
cells, if the collection of blood stem cells is not enough. A catheter (a tube) will be
placed in a large vein in your chest to decrease the number of times you are stuck with a
needle.

Blood stem cells will be collected from your family member, who has been using G-CSF to
prepare for the transplant. They will need to have enough stem cells before
transplantation.

The drugs tacrolimus and methotrexate will be given to ease side effects after the
transplant. Tacrolimus is given by vein or by mouth for 2 to 3 months after the transplant.
During the last month it is given, the dose will be decreased gradually. Methotrexate is
given by vein on Days 1, 3, and 6 after the transplant. An extra dose of methotrexate will
be given on Day 11, if your donor is your parent or child. Blood transfusions may be needed
also.

Sometimes, the transplanted cells attack the normal cells in your body instead of the cancer
cells. This is called graft-versus-host disease (GVHD). The drug methylprednisolone will
be given by vein or by mouth to fight GVHD if it happens.

You must stay in the hospital for about 3 to 4 weeks. You must stay in the Houston area for
about 100 days after the transplant. Blood tests (about 1-2 tablespoons) will be done every
day while you are in the hospital. Chest x-rays, CT scans, and bone scans will be done once
a month during the 100 days, and then every 3 months for the first year after that, so that
researchers can follow your disease response.

If there are no signs of disease after 100 days, treatment will stop. You must return to
the clinic for checkups every 3 months for the first year, then 3 times a year for the next
4 years, and once a year after that. If the disease is still present after 2 months, but
you do not have GVHD, the anti-rejection medicine tacrolimus will be stopped within 2 weeks.
Then if the disease is still present after another 6 weeks, but you do not have GVHD, you
may receive an injection of donor lymphocytes by vein. This treatment may be repeated up to
3 times, with 6 weeks between each time.

If no disease is found or if GVHD occurs, treatment will stop.

This is an investigational study. About 80 participants enrolled in this study will take
part in the stem cell transplant. All will be enrolled at M. D. Anderson Cancer Center.


Inclusion Criteria:



1. For registration: Willing to undergo allogeneic transplantation.

2. For registration: Age equal to or less than 65 years old.

3. For registration: Metastatic RCC with predominant conventional cell type.

4. For registration: Prior nephrectomy.

5. For registration: Stage IV RCC. If patient has prior single brain metastasis treated
with complete surgical resection or stereotactic radiation therapy, no recurrence or
brain edema from the end of treatment for at least 6 months has to be shown by
radiological imaging.

6. For registration: Zubrod performance status < one.

7. For registration: Potential related donor for allogeneic stem cell transplantation.

8. For registration: At least one prior treatment for metastatic RCC. Radiation therapy
or surgery is not counted as a treatment.

9. For registration: Signed an informed consent.

10. For transplantation: Zubrod performance status < one.

11. For transplantation: An HLA-matched (defined as 6/6 matches) related donor.

12. For transplantation: Failed at least one prior treatment for metastatic RCC.
Radiation therapy or surgery is not counted as a treatment.

13. For transplantation: Adequate major organ functions (see section 4.17-4.20).

14. For transplantation: Signed an informed consent for allogeneic stem cell
transplantation.

Exclusion Criteria:

1. For registration: Prior history of allogeneic stem cell transplantation.

2. For registration: Histologic feature with predominant non-conventional cell type.

3. For registration: Multiple brain metastasis.

4. For registration: Life expectancy is severely limited by concomitant illness.

5. For transplantation: Multiple brain metastasis.

6. For transplantation: Life expectancy is severely limited by concomitant illness.

7. For transplantation: Clinically significant active infections.

8. For transplantation: HIV infection.

9. For transplantation: Chronic active hepatitis

10. For transplantation: Pregnant or lactating women.

11. For transplantation: Has all three risk factors: high serum lactate dehydrogenase,
low hemoglobin, high corrected serum calcium.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Survival Rate

Outcome Description:

Number of participants surviving at 4 years compared to total participants, to compare the overall survival of metastatic renal cell carcinoma (RCC) patients undergoing HLA-matched related donor nonmyeloablative allogeneic hematopoietic stem cell transplantation (NST) using fludarabine-melphalan (FM) versus fludarabine-cyclophosphamide (FC) conditioning regimen. Evaulation after 1, 2, 3, 6, 9, & 12 months, then every 4 months for 4 years.

Outcome Time Frame:

Up to 4 years

Safety Issue:

No

Principal Investigator

Naoto Ueno, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

2003-0364

NCT ID:

NCT00429026

Start Date:

January 2004

Completion Date:

March 2008

Related Keywords:

  • Renal Cell Cancer
  • Kidney Cancer
  • Renal Cell Cancer
  • Stem Cell Transplant
  • Cyclophosphamide
  • Fludarabine
  • Melphalan
  • NST
  • Carcinoma, Renal Cell

Name

Location

U.T. M.D. Anderson Cancer CenterHouston, Texas  77030