Stem Cell TransplantationPhase 1NCT00972101
Infusion of Expanded Cord Blood T Cells
A Phase 1 study testing Total Body Irradiation (TBI), Melphalan and Thiotepa in people with Stem Cell Transplantation and Leukemia, run by M.D. Anderson Cancer Center.
Trial summary
The goal of this clinical research study is to learn if treating umbilical cord blood with growth factors before a transplant can help to improve the body's ability to accept the cord blood transplants. Read more about this study
- Who is it for?
- Ages Up to 55 years
- Conditions the study is for
- Stem Cell Transplantation, Leukemia, Lymphoma
- What is being tested?
- Total Body Irradiation (TBI), Melphalan and Thiotepa
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Sep 2009to Sep 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 55 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patient must have one of the following hematologic malignancies:
- AML
- ALL
- CML
- NHL
- HD, or
Show all 24Show fewer
- CLL (Select from Criteria #2 through #7)
- Acute Myelogenous Leukemia (AML), Myelodysplastic Syndrome (MDS; Myelodysplastic syndromes with International Prognostic Scoring System score >2 or myelodysplasia that has not responded to chemotherapy): induction failure, high-risk for relapse 1st remission (with high-risk cytogenetics or FLT3 mutation), 2nd or 3rd complete remission, or 2nd relapse with less than 10% blasts in the bone marrow and/or peripheral blood.
- Acute Lymphoblastic Leukemia (ALL): induction failure, 1st complete remission with Philadelphia chromosome or translocation, 2nd or 3rd complete remission, or 2nd relapse with less than 10% blasts in the bone marrow and/or peripheral blood.
- Chronic Myelogenous Leukemia (CML) second chronic phase, accelerated phase or blast crisis with less than 10% blasts in the bone marrow and/or peripheral blood and failure of at least one tyrosine kinase inhibitor.
- Non-Hodgkin's Lymphoma (NHL): Induction failures, second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant).
- Hodgkin's Disease (HD): Induction failures, second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant).
- Chronic Lymphocytic Leukemia (CLL): Failure of one multi-agent regimen including fludarabine or other nucleoside analog
- Patient's Age Criteria: Age >/= 6 months and </= 55 years
- Performance score of < 3 (Zubrod score).
- Adequate major organ system function as demonstrated by: (SEE CRITERIA #11 through #14)
- Left ventricular ejection function of >/= 50%.
- Pulmonary function test demonstrating a diffusion capacity of at least 50% predicted. If unable to perform pulmonary function test (most children <6 years of age), pulse oximetry >/= 92% on room air.
- Creatinine </= 1.6 mg/dL in adults and </=2 times upper limit of normal in pediatric patients.
- SGPT/bilirubin </= 3.0 x normal.
- Signed informed consent.
- Negative Beta HCG or urine test in females of childbearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization and willing to use an effective contraceptive measure while on the study.
- Cord Blood Requirements: Unrelated CB will be used as a source of hematopoietic support if a 5/6 or 6/6 related or 6/6 unrelated bone marrow donor is not available, or if the tempo of the patient's disease dictates it is not in the patient's best interest to wait for an unrelated marrow donor to be procured. The back up cord blood unit must match at 4 of 6 HLA.
- An unrelated donor, second cord blood transplant, or autologous stem cells harvested prior to high-dose chemotherapy will be used in the event of graft failure. Based on the health status of the patient, autologous harvest may or may not occur. To be determined by the treating physician. The cord blood unit will be identified prior to enrollment in this study.
Who cannot join
- HIV positive (due to the extreme immunosuppressive nature of allogeneic stem cell transplant)
- Patient with active (untreated) CNS disease
- Availability of an appropriate, willing, HLA-matched related marrow donor
- Active invasive infections.
- Pregnant or breast-feeding
About this study
Official title: Infusion of Expanded Cord Blood T Cells Following Cord Blood Transplantation
The goal of this clinical research study is to learn if treating umbilical cord blood with growth factors before a transplant can help to improve the body's ability to accept the cord blood transplants.
Read the detailed description
Umbilical cord blood is a source of stem cells that can be used for transplantation. The major problem with this type of transplant is the small number of stem cells that are available in the cord blood. This delays the recipients body's ability to accept the cord blood. This may also cause the immune system to slow, making infection more likely. One method to help fix this problem is to treat a sample of the cord blood with growth factors, which may promote the growth of the needed T cells before they are given to the recipient as a transplant.
For this study, participants will receive high-dose chemotherapy, then an untreated cord blood cells transplant, and then 14 days later receive the treated cord blood cells transplant.
The Study Drugs:
Melphalan is designed to damage the DNA (the genetic material) of cells, which may cause cancer cells to die.
Thiotepa is designed to the damage DNA, which may cause cancer cells to die
Fludarabine is designed to make cancer cells less able to repair damaged DNA. This may increase the likelihood of the cells dying.
Rituximab is designed to attach to a specific protein on the surface of tumor cells, which may cause them to die.
Etoposide is designed to block cell growth.
Filgrastim is a drug that helps cells in the bone marrow to divide
Anti-thymocyte globulin (ATG) is a drug that helps the immune system by attaching to and inactivating T cells.
Mycophenolate mofetil (MMF) is a drug that suppresses the immune system.
Tacrolimus is a drug that helps the immune system to prevent GVHD.
IL-2 is a protein that is used to help the growth of T cells.
Placement of Central Venous Catheter (CVC):
Before you can have back-up stem cells collected or you receive chemotherapy, you will be required to have a CVC, which is a sterile flexible tube, placed into a large vein in the upper chest while you are under local anesthesia. Children are usually unable to hold still for this procedure and will be given drugs to make them sleep for the procedure. 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. If you are donating back-up cells (as described below) the catheter will be placed the day of the collection. If you are not donating back up cells, the CVC will be placed a few days before admission to the hospital. This catheter will be used to draw blood, give fluids, and give the study drugs.
Collection of "back up" stem cells:
Collection of additional stem cells from the donor of the cord blood will not be possible if the transplant with the cord blood fails. Back-up blood or additional bone marrow will be collected from you and frozen about a week before the high-dose chemotherapy begins. The study doctor will decide to collect or not collect this sample based on the status of the disease. The sample(s) will be collected by leukapheresis or with bone marrow aspirates.
Selection of another donor as the alternate source of stem cells If the cord blood transplant is not successful, you will receive the back-up cells collected before admission as described above. If you are unable to donate these stem cells, for example it they are contamination with tumor cells, a family member or a second cord blood transplant will be used. The potential family member donor will have screening tests performed to find out if they are eligible to donate stem cells.
Leukapheresis:
If you are donating back-up stem cells, before the collection of the blood stem cells, you will be treated with a drug called filgrastim, which will make the stem cells in the marrow easier for the study doctor to collect and help to increase the number of white blood cells. This drug is given through a needle under the skin 1-2 times a day for 3-7 days. When the white cell count is high enough (usually around day 4), your blood stem cells will be collected from your CVC over 3-4 hours/day. The collection process will be repeated daily until a enough stem cells are collected. You will continue to receive filgrastim until all the stem cells are collected.
Bone Marrow Collection:
If the leukapheresis cannot be performed successfully, for example the white blood cell count does not increase enough with the filgrastim, you will have bone marrow collected. You will go to the operating room and be asleep for this. Multiple small bone marrow aspirates will be performed and the marrow collected. Only a small sample of your bone marrow (less than 5%) will be taken. To collect a bone marrow aspirate, an area of the hip is numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large needle.
High-Dose Chemotherapy Administration:
Day 0 is the day of the stem cell transplant, so the negative day numbers are used to describe the treatment days before the transplant. All chemotherapy, fluids, and other drugs that must be given by vein will be infused through the CVC. After the "backup" stem cells are collected, you will be admitted to the hospital on Day -9 to begin receiving fluids. Chemotherapy may be stopped if intolerable side effects occur.
You will be placed in 1 of 2 treatment groups. The study doctors will decide which treatment group will be the best treatment for you. If you are in Group 1, you will receive chemotherapy and the cord blood transfusion. If you are in Group 2, you will receive treatment with chemotherapy, radiation, and the cord blood transfusion.
- If you are in Group 1, you will receive melphalan by vein over 30 minutes as a single dose on Day -8, thiotepa by vein over 4 hours as a single dose on Day -7, followed by fludarabine by vein over about 30 minutes 1 time each day on Days -6 through -3. Rituximab may be given by vein over 4 - 6 hours on Day -9 if the doctor thinks it is necessary.
- If you are in Group 2, you will receive radiation on Days -7,-6, -5 and -4. You will sign a separate consent for the total body irradiation. Then you will be given etoposide by vein over 1-2 hours as a single dose on Day -3. Rituximab may be given by vein over 4-6 hours on Day -8 if the doctor thinks it is necessary.
- Group 1 will receive anti-thymocyte globulin (ATG) by vein over 4-6 hours on the Days -4 and -3 of treatment to lower the chances of the cord blood infusion being rejected.
- Group 2 will receive anti-thymocyte globulin (ATG) by vein over 4-6 hours on the Days -3, -2, and -1 of treatment to lower the chances of the cord blood infusion being rejected.
Cord Blood Infusion:
After your chemotherapy treatment, and total body irradiation (only for Group 2), your cord blood unit will be thawed. The larger portion of the cord blood will be infused through your CVC. A small portion of the cells will be expanded as described below.
Expansion of Cord Blood T Cells:
On Day 0, the smaller unit of your cord blood will be treated at the M. D. Anderson Stem Cell Laboratory with IL-2 and vitamin-like growth factors to produce the needed T cells. At this time, clinical beads will be used to help separate and expand the T cells. This will take 2 weeks. On Day 14, you will then be given the treated cord blood as an infusion through your CVC.
Infusion of Back-Up Cells:
In case the stem cell transplant is rejected by your immune system, and if researchers were unable to collect a sample of your own stem cells, an unrelated donor or a second cord transplant will be used. The cord blood will be treated using a CliniMACs processing device. Mouse protein antibodies are used in CliniMACs processing procedures. Recipients who have pre-existing immunity to these proteins may be at risk for allergic reactions during the infusion of the processed cells. Epinephrine and antihistamines will be available at the recipient's bedside during the peripheral blood progenitor cell (PBSC) infusion to help treat any allergic reactions.
Graft Versus Host Disease (GVHD) Preventive Therapy:
GVHD may result from the transplanted cord blood cells reacting against certain tissues in your body. In an attempt to prevent or decrease the severity of GVHD, you will receive 2 drugs (MMF and tacrolimus).
Mycophenolate mofetil (MMF) pills will be given starting 3 days before your cord blood transplant, and will be continued until Day 100 after the transplant. If you cannot take pills, the drug can be given through your CVC. If you develop GVHD, you may have to continue to take MMF after Day 100.
Tacrolimus will be given 2 days before your transplant as a 24 hour continuous infusion for several weeks. After you have the stem cell transplant and are able to eat and drink, tacrolimus will be given by mouth 2 times a day for up to 6 months. The number of tacrolimus pills may vary depending on the levels of the drug in the blood, but usually you will be given between 1-3 pills each time. If you are not able to swallow pills, a liquid form of this drug is available. This drug is used for about 6-9 months or longer if chronic GVHD occurs.
Length of Study:
You will be monitored closely for the first 100 days after receiving the transplant and then periodically after that. You may remain on study as long as the disease does not return and you do not experience any intolerable side effects. Your participation in this clinical trial may be ended at any time for any reason.
Follow-Up Visits After Transplant:
After you leave the hospital, you will come back for regular visits in the clinic at M. D. Anderson. How often you have follow-up visits may vary, but may be as often as daily.
Blood (about 1-2 tablespoons) will be collected for routine tests. The number of blood and/or urine tests may also vary, but they may be performed daily.
You will have a bone marrow aspirate collected before the transplant, about 30 days after the transplant, and then every 3 months for the first year after the transplant. After that, bone marrow samples will be collected 1 time a year for as long as the doctor thinks is necessary. To collect a bone marrow biopsy, an area of the bone is numbed with anaesthetic and a small amount of bone marrow is withdrawn through a large needle.
Patients with lymphomas and Hodgkin's disease will need CT scans of the chest, abdomen, and pelvis performed within 30 days before the transplant, about 100 days after transplant, and then about every 3 months for the first year. After that, it will be done 1 time every year for as long as the doctor thinks it is necessary.
This is an investigational study. The clinical beads that will be used for this study may be produced by either the University of Pennsylvania or Invitrogen Corporation. All of the study drugs are all FDA approved and commercially available for treatment in adults. These drugs alone or in any combination are not FDA approved for this treatment in children and their use in this study is considered to be experimental.
The CliniMACS processing device used to process the cells for backup infusion is not FDA approved for this use.
Up to 18 patients will take part in this study. All will be enrolled at M. D. Anderson.
- Conditions
- Stem Cell Transplantation, Leukemia, Lymphoma, Pediatric Disorders
- Being tested
- Total Body Irradiation (TBI), Melphalan, Thiotepa, Fludarabine, Rituximab
- Keywords
- Blood And Marrow Transplantation, Leukemia, Lymphoma, Pediatrics, Etoposide, Expanded Cord Blood T Cells, Filgrastim, Fludarabine, Melphalan, Mycophenolate Mofetil, Rituximab, Tacrolimus, Thiotepa, Thymoglobulin, Total Body Irradiation
- Medical subject headings
- Leukemia, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Total Body Irradiation (TBI)Radiation
3 Gy of radiation on Days -7,-6, -5 and -4.
MelphalanDrug
Also called Alkeran
140 mg/m^2 by vein over 30 minutes as a single dose on Day -8
ThiotepaDrug
10 mg/kg by vein over 4 hours as a single dose on Day -7
FludarabineDrug
Also called Fludara, Fludarabine Phosphate
40 mg/m^2 by vein over about 30 minutes 1 time each day on Days -6 through -3.
RituximabDrug
Also called Rituxan
Regimen 1:
375 mg/m^2 may be given by vein over 4 - 6 hours on Day -9 if needed
Regimen 2:
375 mg/m^2 may be given by vein over 4 - 6 hours on Day -8 if needed
EtoposideDrug
Also called VePesid
60 mg/m^2 by vein over 1-2 hours as a single dose on Day -3.
Anti-thymocyte globulin (ATG)Drug
Also called Thymoglublin
Regimen 1:
1.25 and 1.75 mg/kg by vein over 4-6 hours on the Days -4 and -3.
Regimen 2:
0.5, 1.0 and 1.5 mg/kg by vein over 4-6 hours on respective Days -3, -2, and -1.
Mycophenolate Mofetil (MMF)Drug
Also called CellCept
15 mg/kg pills twice a day starting on day -3, and continued until Day 100+ after transplant (1 gram may be given by vein if necessary).
TacrolimusDrug
Also called FK506, Prograf
0.03 mg/kg by vein Day -2 as 24 hour continuous infusion for several weeks. After stem cell transplant, tacrolimus given by mouth 2 times a day for up to 6 months.
Cord Blood InfusionProcedure or surgery
Also called Cord Blood T Cells Infusion
Cord blood infusion of larger portion through vein using Central Venous Catheter (CVC) on Day 0.
G-CSFDrug
Also called Filgrastim, Neupogen
5 mcg/kg day subcutaneously (may round up to the next vial) beginning on day +1 and continuing till absolute neutrophil count is > 2.5 x 10e^9/L.
Ex vivo expanded T cell InfusionProcedure or surgery
Infusion by vein of treated cord blood beginning dose of 1 x 10e^5 T cells/kg on Day 14+.
| Study group | Role | What they receive |
|---|---|---|
| Regimen 1: No TBI | Experimental | High Dose Chemotherapy without Total Body Irradiation (TBI) Receives: Drug: Melphalan; Drug: Thiotepa; Drug: Fludarabine; Drug: Rituximab; Drug: Anti-thymocyte globulin (ATG); Drug: Mycophenolate Mofetil (MMF); Drug: Tacrolimus; Procedure: Cord Blood Infusion; Drug: G-CSF; Procedure: Ex vivo expanded T cell Infusion |
| Regimen 2: TBI | Experimental | High Dose Chemotherapy with Total Body Irradiation (TBI) Receives: Radiation: Total Body Irradiation (TBI); Drug: Rituximab; Drug: Etoposide; Drug: Anti-thymocyte globulin (ATG); Drug: Mycophenolate Mofetil (MMF); Drug: Tacrolimus; Procedure: Cord Blood Infusion; Drug: G-CSF; Procedure: Ex vivo expanded T cell Infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
Measured: Days 14 to 100
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2009 (estimated)
- Study startSep 2009
- Primary completionSep 2011
- Study completionSep 2011
Why it stopped: Development of other studies led to termination without recruitment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stem Cell TransplantationStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Laura L. Worth, MD, PHD, Study chair, UT MD Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00972101
- Sponsor's protocol ID
- 2006-0075
- Status last verified
- Oct 2012
- First submitted
- 3 Sep 2009
- Last updated
- 11 Oct 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Infusion of Expanded Cord Blood T Cells Following Cord Blood Transplantation
- ClinicalTrials.gov ID
- NCT00972101
- Acronym / sponsor ID
- 2006-0075
- Conditions
- Stem Cell Transplantation, Leukemia, Lymphoma, Pediatric Disorders
- Keywords
- Blood And Marrow Transplantation, Leukemia, Lymphoma, Pediatrics, Etoposide, Expanded Cord Blood T Cells, Filgrastim, Fludarabine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Development of other studies led to termination without recruitment.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- Sep 2009
- Primary completion
- Sep 2011 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 4 Sep 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical research study is to learn if treating umbilical cord blood with growth factors before a transplant can help to improve the body's ability to accept the cord blood transplants.
Detailed description
Umbilical cord blood is a source of stem cells that can be used for transplantation. The major problem with this type of transplant is the small number of stem cells that are available in the cord blood. This delays the recipients body's ability to accept the cord blood. This may also cause the immune system to slow, making infection more likely. One method to help fix this problem is to treat a sample of the cord blood with growth factors, which may promote the growth of the needed T cells before they are given to the recipient as a transplant.
For this study, participants will receive high-dose chemotherapy, then an untreated cord blood cells transplant, and then 14 days later receive the treated cord blood cells transplant.
The Study Drugs:
Melphalan is designed to damage the DNA (the genetic material) of cells, which may cause cancer cells to die.
Thiotepa is designed to the damage DNA, which may cause cancer cells to die
Fludarabine is designed to make cancer cells less able to repair damaged DNA. This may increase the likelihood of the cells dying.
Rituximab is designed to attach to a specific protein on the surface of tumor cells, which may cause them to die.
Etoposide is designed to block cell growth.
Filgrastim is a drug that helps cells in the bone marrow to divide
Anti-thymocyte globulin (ATG) is a drug that helps the immune system by attaching to and inactivating T cells.
Mycophenolate mofetil (MMF) is a drug that suppresses the immune system.
Tacrolimus is a drug that helps the immune system to prevent GVHD.
IL-2 is a protein that is used to help the growth of T cells.
Placement of Central Venous Catheter (CVC):
Before you can have back-up stem cells collected or you receive chemotherapy, you will be required to have a CVC, which is a sterile flexible tube, placed into a large vein in the upper chest while you are under local anesthesia. Children are usually unable to hold still for this procedure and will be given drugs to make them sleep for the procedure. 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. If you are donating back-up cells (as described below) the catheter will be placed the day of the collection. If you are not donating back up cells, the CVC will be placed a few days before admission to the hospital. This catheter will be used to draw blood, give fluids, and give the study drugs.
Collection of "back up" stem cells:
Collection of additional stem cells from the donor of the cord blood will not be possible if the transplant with the cord blood fails. Back-up blood or additional bone marrow will be collected from you and frozen about a week before the high-dose chemotherapy begins. The study doctor will decide to collect or not collect this sample based on the status of the disease. The sample(s) will be collected by leukapheresis or with bone marrow aspirates.
Selection of another donor as the alternate source of stem cells If the cord blood transplant is not successful, you will receive the back-up cells collected before admission as described above. If you are unable to donate these stem cells, for example it they are contamination with tumor cells, a family member or a second cord blood transplant will be used. The potential family member donor will have screening tests performed to find out if they are eligible to donate stem cells.
Leukapheresis:
If you are donating back-up stem cells, before the collection of the blood stem cells, you will be treated with a drug called filgrastim, which will make the stem cells in the marrow easier for the study doctor to collect and help to increase the number of white blood cells. This drug is given through a needle under the skin 1-2 times a day for 3-7 days. When the white cell count is high enough (usually around day 4), your blood stem cells will be collected from your CVC over 3-4 hours/day. The collection process will be repeated daily until a enough stem cells are collected. You will continue to receive filgrastim until all the stem cells are collected.
Bone Marrow Collection:
If the leukapheresis cannot be performed successfully, for example the white blood cell count does not increase enough with the filgrastim, you will have bone marrow collected. You will go to the operating room and be asleep for this. Multiple small bone marrow aspirates will be performed and the marrow collected. Only a small sample of your bone marrow (less than 5%) will be taken. To collect a bone marrow aspirate, an area of the hip is numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large needle.
High-Dose Chemotherapy Administration:
Day 0 is the day of the stem cell transplant, so the negative day numbers are used to describe the treatment days before the transplant. All chemotherapy, fluids, and other drugs that must be given by vein will be infused through the CVC. After the "backup" stem cells are collected, you will be admitted to the hospital on Day -9 to begin receiving fluids. Chemotherapy may be stopped if intolerable side effects occur.
You will be placed in 1 of 2 treatment groups. The study doctors will decide which treatment group will be the best treatment for you. If you are in Group 1, you will receive chemotherapy and the cord blood transfusion. If you are in Group 2, you will receive treatment with chemotherapy, radiation, and the cord blood transfusion.
- If you are in Group 1, you will receive melphalan by vein over 30 minutes as a single dose on Day -8, thiotepa by vein over 4 hours as a single dose on Day -7, followed by fludarabine by vein over about 30 minutes 1 time each day on Days -6 through -3. Rituximab may be given by vein over 4 - 6 hours on Day -9 if the doctor thinks it is necessary.
- If you are in Group 2, you will receive radiation on Days -7,-6, -5 and -4. You will sign a separate consent for the total body irradiation. Then you will be given etoposide by vein over 1-2 hours as a single dose on Day -3. Rituximab may be given by vein over 4-6 hours on Day -8 if the doctor thinks it is necessary.
- Group 1 will receive anti-thymocyte globulin (ATG) by vein over 4-6 hours on the Days -4 and -3 of treatment to lower the chances of the cord blood infusion being rejected.
- Group 2 will receive anti-thymocyte globulin (ATG) by vein over 4-6 hours on the Days -3, -2, and -1 of treatment to lower the chances of the cord blood infusion being rejected.
Cord Blood Infusion:
After your chemotherapy treatment, and total body irradiation (only for Group 2), your cord blood unit will be thawed. The larger portion of the cord blood will be infused through your CVC. A small portion of the cells will be expanded as described below.
Expansion of Cord Blood T Cells:
On Day 0, the smaller unit of your cord blood will be treated at the M. D. Anderson Stem Cell Laboratory with IL-2 and vitamin-like growth factors to produce the needed T cells. At this time, clinical beads will be used to help separate and expand the T cells. This will take 2 weeks. On Day 14, you will then be given the treated cord blood as an infusion through your CVC.
Infusion of Back-Up Cells:
In case the stem cell transplant is rejected by your immune system, and if researchers were unable to collect a sample of your own stem cells, an unrelated donor or a second cord transplant will be used. The cord blood will be treated using a CliniMACs processing device. Mouse protein antibodies are used in CliniMACs processing procedures. Recipients who have pre-existing immunity to these proteins may be at risk for allergic reactions during the infusion of the processed cells. Epinephrine and antihistamines will be available at the recipient's bedside during the peripheral blood progenitor cell (PBSC) infusion to help treat any allergic reactions.
Graft Versus Host Disease (GVHD) Preventive Therapy:
GVHD may result from the transplanted cord blood cells reacting against certain tissues in your body. In an attempt to prevent or decrease the severity of GVHD, you will receive 2 drugs (MMF and tacrolimus).
Mycophenolate mofetil (MMF) pills will be given starting 3 days before your cord blood transplant, and will be continued until Day 100 after the transplant. If you cannot take pills, the drug can be given through your CVC. If you develop GVHD, you may have to continue to take MMF after Day 100.
Tacrolimus will be given 2 days before your transplant as a 24 hour continuous infusion for several weeks. After you have the stem cell transplant and are able to eat and drink, tacrolimus will be given by mouth 2 times a day for up to 6 months. The number of tacrolimus pills may vary depending on the levels of the drug in the blood, but usually you will be given between 1-3 pills each time. If you are not able to swallow pills, a liquid form of this drug is available. This drug is used for about 6-9 months or longer if chronic GVHD occurs.
Length of Study:
You will be monitored closely for the first 100 days after receiving the transplant and then periodically after that. You may remain on study as long as the disease does not return and you do not experience any intolerable side effects. Your participation in this clinical trial may be ended at any time for any reason.
Follow-Up Visits After Transplant:
After you leave the hospital, you will come back for regular visits in the clinic at M. D. Anderson. How often you have follow-up visits may vary, but may be as often as daily.
Blood (about 1-2 tablespoons) will be collected for routine tests. The number of blood and/or urine tests may also vary, but they may be performed daily.
You will have a bone marrow aspirate collected before the transplant, about 30 days after the transplant, and then every 3 months for the first year after the transplant. After that, bone marrow samples will be collected 1 time a year for as long as the doctor thinks is necessary. To collect a bone marrow biopsy, an area of the bone is numbed with anaesthetic and a small amount of bone marrow is withdrawn through a large needle.
Patients with lymphomas and Hodgkin's disease will need CT scans of the chest, abdomen, and pelvis performed within 30 days before the transplant, about 100 days after transplant, and then about every 3 months for the first year. After that, it will be done 1 time every year for as long as the doctor thinks it is necessary.
This is an investigational study. The clinical beads that will be used for this study may be produced by either the University of Pennsylvania or Invitrogen Corporation. All of the study drugs are all FDA approved and commercially available for treatment in adults. These drugs alone or in any combination are not FDA approved for this treatment in children and their use in this study is considered to be experimental.
The CliniMACS processing device used to process the cells for backup infusion is not FDA approved for this use.
Up to 18 patients will take part in this study. All will be enrolled at M. D. Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Regimen 1: No TBI | Experimental | Drug: Melphalan, Drug: Thiotepa, Drug: Fludarabine, Drug: Rituximab, Drug: Anti-thymocyte globulin (ATG), Drug: Mycophenolate Mofetil (MMF), Drug: Tacrolimus, Procedure: Cord Blood Infusion, Drug: G-CSF, Procedure: Ex vivo expanded T cell InfusionHigh Dose Chemotherapy without Total Body Irradiation (TBI) |
| Regimen 2: TBI | Experimental | Radiation: Total Body Irradiation (TBI), Drug: Rituximab, Drug: Etoposide, Drug: Anti-thymocyte globulin (ATG), Drug: Mycophenolate Mofetil (MMF), Drug: Tacrolimus, Procedure: Cord Blood Infusion, Drug: G-CSF, Procedure: Ex vivo expanded T cell InfusionHigh Dose Chemotherapy with Total Body Irradiation (TBI) |
Who may qualify
- Ages
- Up to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (24 listed)
- Patient must have one of the following hematologic malignancies:
- Acute Myelogenous Leukemia (AML), Myelodysplastic Syndrome (MDS; Myelodysplastic syndromes with International Prognostic Scoring System score >2 or myelodysplasia that has not responded to chemotherapy): induction failure, high-risk for relapse 1st remission (with high-risk cytogenetics or FLT3 mutation), 2nd or 3rd complete remission, or 2nd relapse with less than 10% blasts in the bone marrow and/or peripheral blood.
- Acute Lymphoblastic Leukemia (ALL): induction failure, 1st complete remission with Philadelphia chromosome or translocation, 2nd or 3rd complete remission, or 2nd relapse with less than 10% blasts in the bone marrow and/or peripheral blood.
- Chronic Myelogenous Leukemia (CML) second chronic phase, accelerated phase or blast crisis with less than 10% blasts in the bone marrow and/or peripheral blood and failure of at least one tyrosine kinase inhibitor.
- Non-Hodgkin's Lymphoma (NHL): Induction failures, second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant).
Key exclusion criteria (5 listed)
- HIV positive (due to the extreme immunosuppressive nature of allogeneic stem cell transplant)
- Patient with active (untreated) CNS disease
- Availability of an appropriate, willing, HLA-matched related marrow donor
- Active invasive infections.
- Pregnant or breast-feeding
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Total Body Irradiation (TBI)3 Gy of radiation on Days -7,-6, -5 and -4. | Radiation | Regimen 2: TBI |
| MelphalanAlso: Alkeran140 mg/m^2 by vein over 30 minutes as a single dose on Day -8 | Drug | Regimen 1: No TBI |
| Thiotepa10 mg/kg by vein over 4 hours as a single dose on Day -7 | Drug | Regimen 1: No TBI |
| FludarabineAlso: Fludara, Fludarabine Phosphate40 mg/m^2 by vein over about 30 minutes 1 time each day on Days -6 through -3. | Drug | Regimen 1: No TBI |
| RituximabAlso: RituxanRegimen 1: 375 mg/m^2 may be given by vein over 4 - 6 hours on Day -9 if needed Regimen 2: 375 mg/m^2 may be given by vein over 4 - 6 hours on Day -8 if needed | Drug | Regimen 1: No TBI, Regimen 2: TBI |
| EtoposideAlso: VePesid60 mg/m^2 by vein over 1-2 hours as a single dose on Day -3. | Drug | Regimen 2: TBI |
| Anti-thymocyte globulin (ATG)Also: ThymoglublinRegimen 1: 1.25 and 1.75 mg/kg by vein over 4-6 hours on the Days -4 and -3. Regimen 2: 0.5, 1.0 and 1.5 mg/kg by vein over 4-6 hours on respective Days -3, -2, and -1. | Drug | Regimen 1: No TBI, Regimen 2: TBI |
| Mycophenolate Mofetil (MMF)Also: CellCept15 mg/kg pills twice a day starting on day -3, and continued until Day 100+ after transplant (1 gram may be given by vein if necessary). | Drug | Regimen 1: No TBI, Regimen 2: TBI |
| TacrolimusAlso: FK506, Prograf0.03 mg/kg by vein Day -2 as 24 hour continuous infusion for several weeks. After stem cell transplant, tacrolimus given by mouth 2 times a day for up to 6 months. | Drug | Regimen 1: No TBI, Regimen 2: TBI |
| Cord Blood InfusionAlso: Cord Blood T Cells InfusionCord blood infusion of larger portion through vein using Central Venous Catheter (CVC) on Day 0. | Procedure or surgery | Regimen 1: No TBI, Regimen 2: TBI |
| G-CSFAlso: Filgrastim, Neupogen5 mcg/kg day subcutaneously (may round up to the next vial) beginning on day +1 and continuing till absolute neutrophil count is > 2.5 x 10e^9/L. | Drug | Regimen 1: No TBI, Regimen 2: TBI |
| Ex vivo expanded T cell InfusionInfusion by vein of treated cord blood beginning dose of 1 x 10e^5 T cells/kg on Day 14+. | Procedure or surgery | Regimen 1: No TBI, Regimen 2: TBI |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: Days 14 to 100
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Oct 2012.
- UT MD Anderson Cancer Center websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Laura L. Worth, MD, PHD study chair
UT MD Anderson Cancer Center
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Total Body Irradiation (TBI), Melphalan and Thiotepa in people with Stem Cell Transplantation and Leukemia, run by M.D. Anderson Cancer Center.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 11 Oct 2012. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) (time frame: Days 14 to 100). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Oct 2012.