Research Consent Form
Dana-Farber/ Harvard Cancer Center
BIDMC/BWH/CH/DFCI/MGH/Partners Network Affiliates
OPRS 11-04
Supercedes Version Dated: 02-04
Protocol Title: Phase II Study Of Parathyroid Hormone following Sequential Unrelated Cord Blood Transplantation
DFHCC Principal Research Doctor/institution: Karen Ballen, M.D.
DFHCC Site-Responsible Research Doctor(s)/institution(s): Joseph Antin, MD, DFCI, David Avigan, MD, Beth Israel Deaconess
Myeloablative Regimen
Introduction
We are inviting you to participate in a research study. Research is a way of gaining new knowledge. A subject is a person who is being studied by the researchers. The title of the study is stated above. This form was created to help explain to you the nature of this study and if you choose to participate, it will be used to document your agreement to be part of this study.
You are being invited to take part in this study because you have an illness that can be treated with a bone marrow or blood transplantation. Since you do not have a family member or volunteer bone marrow donor whose immune system matches your immune system, you are eligible to receive a cord blood transplant. Cord blood, which is collected from the umbilical cord after a woman gives birth, contains blood stem cells, which are cells that can grow and produce all the different parts of your blood as well as your immune system. Since the number of stem cells that are present in 1 cord blood is small, in this study we will transplant you with 2 cord blood units given on the same day. This is called double or sequential cord blood transplantation. This is a newer way of performing cord blood transplantation and may speed the recovery of normal blood counts.
About 25 people will take part in this study through the Dana-Farber/Harvard Cancer Center, and about 40 patients will take part overall including at several sites in the United States.
This consent form will give you the information you will need to understand why this study is being done and why you are being invited to participate. It will also describe what you need to do to participate and state any possible risks, inconveniences, or discomforts that you may have while participating. If you decide to participate, you will be asked to sign this form and it will be a record of your agreement to participate. You will be given a copy of this form.
If you do sign this consent form, you will first need to be evaluated by the study doctors to see if you can be in the study. This is called screening. The study has eligibility requirements that must be met. If the screening tests show you can be in the study, you will be able to start on the study treatment. If the study doctor feels the results of these tests show that you cannot be in the study, you will not be able to start on study treatment. This is done for safety reasons.
We encourage you to take some time to think this over and to discuss it with your family, friends and doctor. We also encourage you to ask questions now and at any time.
Why Is This Study Being Done?
The purpose of this study is to measure the effectiveness of a drug, parathyroid hormone or PTH, in shortening the amount of time (days to engraftment) it takes your white blood cells to return after transplantation. Since your white blood cells help to fight infection and infection is common after cord blood transplantation, the hope is that the PTH will help to decrease the risk of infection after cord blood transplantation. PTH may work by affecting the places in the bone where blood cells are made, called the stem cell niche.
This study is called a Phase II clinical trial. Phase II trials are the second step in the development of investigational drugs. Investigational means that the drugs are still being studied and that study doctors are trying to find out more about them. The FDA has approved the drug parathyroid hormone for use in patients with osteoporosis (bone thinning) but we do not yet know if PTH is useful after cord blood transplantation.
The primary purpose of this study is to test the effectiveness of the study drug, PTH, in decreasing the number of days until your white blood cell counts return after cord blood transplantation.
A secondary purpose of this study is to learn more about cord blood transplantation.
Since the treatments given to destroy your cancer cells, cyclophosphamide, total body radiation, and fludarabine, the medicines to prevent graft versus host disease, tacrolimus and cellcept, and the PTH all contribute to the return of white blood cells after transplant, all are discussed in this consent form. It is the use of PTH in the setting of double cord blood transplantation that is investigational.
What Other Options Are There?
Taking part in this study is your choice. Instead of voluntarily joining this study, you have these options:
· Double cord blood transplantation without using PTH
· Standard therapy, which may consist of further chemotherapy, or transplant from another donor source if one is available.
· Transplantation that either uses a single cord blood unit or different chemotherapy drugs.
· Other investigational treatments that may be available to you, or
· Getting comfort care, also called palliative care. This type of care helps reduce pain, tiredness, appetite problems and other problems caused by the cancer. It does not treat the cancer directly, but instead tries to improve how you feel. Comfort care tries to keep you as active and comfortable as possible.
These treatments could be given either alone or in combination with each other.
The study doctor can tell you more about your condition and the possible risks and benefits of the different treatments. Please talk to your study doctor about these and other options.
What Is Involved in the Study?
After signing this consent form, and before you begin the study, you will need to have the following tests or procedures to find out if you can be in the study. These tests and procedures are part of regular cancer care and may be done even if you don’t join the study. (If you have had some of these tests or procedures recently, they may not have to be repeated. This will be up to your study doctor.)
· Complete physical exam and medical history
· Blood test (2-3 tablespoons) for routine laboratory tests
· Disease evaluation (x-rays or CT scans, for example)
· Performance status assessment to see how well you are able to perform your daily activities
· Blood tests to find the best-matched cord blood units to your immune system
· Blood tests (approximately 5 tablespoons) performed to assess your immune function (blood tests that may predict your ability to fight infection)
· Bone marrow aspirate and biopsy to look at your blood forming cells.
· EKG or electrocardiogram – a test of the electrical function of your heart
· Evaluation by a dentist
· Pulmonary function tests to measure how well your lungs are performing.
· Echocardiogram (sound wave study) of the heart, or nuclear medicine test to measure the pumping function of your heart
If these tests show you are eligible to participate in this study and you agree to take part in this study, you will then receive the treatment as both an inpatient and outpatient.
The study treatment consists of the following procedures:
· Intravenous (IV) Catheter: As an outpatient, before your transplant, an intravenous (IV, meaning in your vein) catheter will be placed in one of the large veins in your upper chest underneath the collarbone. It will reduce the need for frequent needle punctures in your arm. A separate consent form will need to be signed for this procedure, which describes the actual placement of the device in detail. This catheter will stay in place throughout your transplant, approximately 1 to 2 months (longer if there is a continued need for the catheter). It will be used for drawing blood, receiving blood products and IV medications, and for transplanting the cord blood units.
· Conditioning Therapy: This is the chemotherapy portion of your treatment. It consists of two intravenous medications, given through the intravenous catheter, and radiation therapy treatments. The information below will use a negative symbol in front of each day that is before your transplant.
o You will receive the drug, fludarabine, IV for three days (Days –6,-5,-4) before your transplant.
o You will receive the drug, cyclophosphamide, IV for two days (Days –5,-4) before your transplant.
o You will receive radiation therapy treatments, called total body radiation (TBI) twice daily for three days (Days-3,-2,-1) and once on the morning of your transplant day (Day 0).
Both these drugs and the TBI are given to help destroy your cancer, as well as suppress your immune system to allow the cord blood cells to survive and reproduce.
· Immunosupression Therapy: Starting 3 days before your transplant and every day for 6-9 months after your transplant, you will receive the drugs tacrolimus and mycophenolate mofetil (MMF). You will take both of these drugs either by mouth or by IV through the intravenous catheter twice daily. If you vomit a pill right after taking it, the dose will be repeated. These drugs are used to prevent graft versus host disease (GVHD), a serious complication of transplantation. You will be taking these drugs for several months after the transplant.
· Infusion of Cord Blood Units: After you complete your conditioning therapy (chemotherapy and radiation treatments), you will have your transplant. Each cord blood unit will be thawed and washed in our laboratory and given to you through your central venous catheter. The cord blood units will be given to you 2-5 hours apart. To help with cell count recovery (return of cell counts to normal), you will be given the medication G-CSF starting on day five after your transplant, until your white blood cells recover. G-CSF is a growth factor that will be used to speed up the recovery of white blood cells after your transplant.
· Parathyroid Hormone: Starting on Day 1 after your transplant, you will receive PTH daily through several injections just under the skin (“subcutaneous” injection). PTH is given to help aid engraftment and to help re-strengthen the immune system.
o The dose you take on Day +1 will be increased on Day +2, and again for Day +3. Once established, the dose will remain the same from Day +4 to Day +29.
o PTH will initially be given in the hospital. If you are discharged and still need PTH, you can come to the outpatient clinic to receive the injection, or you may take it at home with the help of a visiting nurse or a family member. You and/or a family member will be trained in the technique of subcutaneous injection.
· Supportive care/transfusions: You will be treated with antibiotics to prevent infection. You may receive transfusions of red blood cells (blood cells that carry oxygen) and platelets (blood cells that prevent bruising and bleeding). After you recover from the transplant, you will have repeat CT scans and x-rays, along with bone marrow aspirates and biopsies to assess your cancer. Often these tests are done as routine care after transplant.
· Blood Tests: You will have blood drawn frequently (about 3 tablespoons per day) to test whether your donor’s immune cells have engrafted or taken in your system. Blood levels of tacrolimus will also be checked frequently.
Optional Research
As an optional part of this research study, we are asking if you will allow us to draw some additional blood to study changes in the immune system after transplant. If you agree, about 4 teaspoons of blood will be taken at 5 different times: once before transplant; at 4 weeks; at 100 days; at one year; and at two years after transplant. If you decide you do not want to participate in this optional part of the study, you can still take part in the main study.
How Long Will I Be in the Study?
The average hospital stay for cord blood transplant is 5-6 weeks, but if a complication develops, you could be hospitalized for longer. You will start receiving study treatment medication about 6 days before your cord blood transplant, and continue for at least an additional 6-9 months after your transplant.
Follow-up visits will continue every 6 months after your last treatment dose, for up to 2 years. Then they will be scheduled yearly. After that you will be contacted periodically to see how you are doing.
What Are the Risks or Discomforts of the Study?
There are risks to taking part in clinical trials. All chemotherapy drugs have side effects, which can be anything from mild and reversible to severe, long-lasting and possibly life threatening. Since most anticancer drugs cause the rapidly dividing cancer cells in your body to slow down, these drugs can also cause other rapidly dividing cells in your body to slow down. These include the blood cells that help to fight infection (white blood cells), the blood cells that help the blood clot (platelets) and the blood cells that carry oxygen in your body (red blood cells). If your blood cell counts fail to recover you may require transfusions, hospitalization, and treatment with antibiotics. Any of these problems can be serious, life threatening, or fatal.
Other common side effects of chemotherapy are hair loss, mild to moderate nausea, vomiting, and loss of appetite. Anti-nausea medications can be prescribed to help relieve your symptoms. Many people on chemotherapy experience loose stools or diarrhea.