Trial of Two Stem Cell Doses To Reduce Transplant Induced Symptom Burden
Trial of Two Stem Cell Doses To Reduce Transplant Induced Symptom Burden
The goal of this clinical research study is to learn whether higher doses of stem cells can
 help to decrease the symptoms that occur after melphalan. Another goal of the study is to see
 how the dose of infused stem cells affects the levels of certain proteins in your blood.
 Researchers also want to learn how the dose of stem cells that you receive affects the
 quality of your life during the weeks after the transplant procedure.
Stem cells are found in the bone marrow and bloodstream, and they rebuild blood, bone marrow,
 and the immune system. This study uses autologous stem cells, which are stem cells collected
 from your own blood. Melphalan is designed to damage the DNA (the genetic material) of cells,
 which may cause cancer cells to die. Granulocyte-colony stimulating factor (G-CSF) is
 designed to help the bone marrow to make more white blood cells. G-CSF is used in this study
 to help move your stem cells out of the bone marrow and into the bloodstream. If your doctor
 decides it is needed, you will also receive chemotherapy to help your blood stem cells move
 out of your bone marrow and into your blood. This allows the stems cells to be collected.
 Researchers also want to learn how the dose of infused stem cells affects the levels of
 certain cytokines in your blood. Cytokines are proteins that can cause symptoms such as
 fatigue and fever.

 Treatment Plan:

 If you are found to be eligible to take part in this study, you will need to have a central
 venous catheter (CVC) placed. A CVC is a flexible sterile tube that will be placed into a
 large vein that runs under your collarbone. Having the CVC allows blood to be drawn and
 medications to be given more easily and with less discomfort. You will be asked to sign a
 separate consent form to have the CVC placed, and the procedure will be more fully explained
 to you at that time.

 If your doctor decides it is needed, you will receive chemotherapy to help your blood stem
 cells move out of your bone marrow and into your blood. You will be asked to sign a separate
 consent form for this chemotherapy.

 Starting on the day of the stem cell infusion, you will receive G-CSF by injection under your
 skin. You will have the G-CSF injected once or twice a day for about 10 days. The injections
 may be given at home, if possible. You will be taught how to inject the G-CSF, or someone who
 agrees to be responsible for giving you the injections may also be taught.

 Once the number of stem cells in your bloodstream is high enough, the stem cells will be
 collected over the course of 2-5 days. You will be asked to sign a separate consent form for
 the stem cell collection, and the process will be described in more detail at that time. Not
 counting the blood that is returned to you, about 32 tablespoons of blood will be drawn for
 the stem cell collection.

 You will keep receiving the daily G-CSF injections on the days that your stem cells are
 collected. A procedure called apheresis will be used to collect the stem cells. During the
 apheresis, blood will be collected either through your CVC or from a vein in one arm. The
 blood will be processed through a machine to remove the stem cells, and then the rest of the
 blood will be returned to you through your CVC or through a vein in the other arm. The
 apheresis procedure will last several hours each time. You will be asked to sign a separate
 consent form for the apheresis procedure. You will have enough stem cells collected so that
 you will be able to have either 1 transplant with high doses of stem cells or 2 transplants
 with standard doses of stem cells. Your stem cells will be frozen (cryopreserved) until being
 given back to you.

 About 2 weeks after your stem cells have been collected, you will have chemotherapy with
 melphalan. The melphalan will be given over 30 minutes through your CVC. Since this treatment
 destroys the normal bone marrow in addition to the myeloma cells, your blood stem cells must
 be given back to you. This is because blood stem cells are able to refill the bone marrow. If
 your doctor thinks it is needed, you may be admitted to the hospital the day before you
 receive melphalan to receive fluids by vein to hydrate you.

 Two (2) days after receiving the melphalan, your previously collected stem cells will be
 unfrozen and given back to you through your CVC, similar to a blood transfusion. This is
 called an autologous stem cell transplant. You will be randomly assigned (as in the toss of a
 coin) to receive either a standard amount of stem cells or an experimental amount of stem
 cells. You have a 50/50 chance of being assigned to either group. After you receive your stem
 cells, you will be given G-CSF as an injection under the skin. You will keep having G-CSF
 injections until your white blood cell count returns to normal.

 After your stem cells have been given back to you, it will take about 2 weeks for enough
 blood cells to be made. During this time, it is possible that you might not be making any
 blood cells. If this happens, you may need to have several red blood cell and platelet
 transfusions. You will receive antibiotics if infections occur, and you may need to be given
 feedings through the CVC.

 The entire stem cell transplantation process will be done on an outpatient basis, if
 possible. Otherwise, you may need to stay in the hospital for up to 3-4 weeks.

 After the stem cell transplant is completed, you will need to return to the clinic for
 follow-up visits at least once a week for a month, or more often if the doctor feels it is
 necessary. The follow-up visits will include the same tests and procedures as is standard of
 care. Research blood (about 2-4 teaspoons each time) will also be drawn on Day -2, Day 0, Day
 +3, Day +5, and Day +7; twice a week during weeks 2 and 3; and then once during week 4 for
 immune system tests.

 Questionnaires and Physical Tests:

 At several times during the study, you will be asked to complete a questionnaire about your
 symptoms and quality of life. Sometimes the questionnaire will be done over the phone with an
 automated phone system. Rating your symptoms using the telephone system should take less than
 5 minutes for each call. The rest of the time questionnaires will be performed on paper and
 through phone interviews. You will also be asked to perform physical tests, including walking
 for 6 minutes and getting in and out of a chair.

 The research nurse will teach you how to use the telephone system for measuring symptoms and
 your quality of life. You will perform the physical function tests and complete the symptom
 questionnaire. You will also have tests of the sensitivity of the nerves in your arms and
 legs. Blood (about 4-5 tablespoons) will be drawn for routine tests. Completing the
 questionnaires and tasks at this first visit should take about an hour.

 During your hospital stay or clinic visits for the stem cell transplant, you will be asked on
 Day -2 (2 days before the transplant), Day 0, Day +3, Day +5, and Day +7 after the transplant
 to fill out a paper questionnaire that measures symptoms. You will also be asked on the same
 days to complete brief tasks that measure physical function.

 During Weeks 2 and 3 you will be asked to fill out the paper questionnaire twice a week and
 complete the tasks of physical function once a week. During Week 4, you will be asked to fill
 out the questionnaire once and complete the tasks of physical function once. During Week 4,
 the sensory testing of the nerves in your arms and legs will also be repeated. On the same
 day as the physical tests, the research nurse will ask you to practice using the telephone
 system for measuring symptoms.

 After you leave the hospital or clinic, the telephone system will call you at home. The calls
 will occur 1 time a week from Week 5 through Week 12 after the transplant, then 1 time a
 month during Months 3, 6, and 12 (+/- 1 month). The telephone system will ask you to rate how
 strong and tolerable the symptoms are, and how much the symptoms interfere with your daily
 life.

 During the clinic visit that occurs about 90 days after the transplant, you will be asked to
 complete brief tasks that measure physical function, and you will also have the last test of
 the nerves in your arms and legs.

 You will be on study for about 1 year.

 This is an investigational study. Melphalan with autologous stem cell transplantation is
 FDA-approved for the treatment of myeloma and amyloidosis. The medications and treatment for
 this study are all commercially available. Up to 100 patients will take part in this study.
 All will be enrolled at MD Anderson.
Inclusion Criteria:

 1. Patients with multiple myeloma over the age of 60 in any of the following disease
 categories: a) Primary refractory disease b) Consolidation of a first partial or
 complete remission. OR

 2. Patients with primary amyloidosis.

 3. Zubrod PS of <2 or Karnofsky >/= 70.

 4. Left ventricular ejection fraction >/= 40%. No uncontrolled arrhythmias or symptomatic
 cardiac disease.

 5. Forced expiratory volume at one second (FEV1), forced vital capacity (FVC) and
 diffusion capacity of lung for carbon monoxide (DLCO) >/= 40%. No symptomatic
 pulmonary disease.

 6. Serum bilirubin </= 2 X upper limit of normal, serum glutamate pyruvate transaminase
 (SGPT) </= 4 X upper limit of normal. No evidence of chronic active hepatitis or
 cirrhosis. No effusion or ascites >1L prior to drainage.

 7. HIV-negative.

 8. Patient is not pregnant.

 9. Patient or guardian able to sign informed consent.

 10. Have greater than or equal to 10 x 10 e 6 CD34+ cells per kg of autologous stem cells
 cryopreserved for stem cell transplantation, procured with 5 or fewer apheresis
 collections.

 Exclusion Criteria:

 1) Patients unable to perform MDASI assessments due to language or cultural barriers.