Leukemia, Lymphocytic, AcutePhase 2NCT00067002
Randomized Double Cord Blood Transplant Study
A Phase 2 study testing Expanded allogeneic cord blood (CB), One Unmanipulated and One Expanded Cord Blood Unit and Rituxan in people with Leukemia, Lymphocytic, Acute and Leukemia, Myelocytic, Acute, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The goal of this clinical research study is to learn if combining cord blood units to make the cells "take" faster in recipients will help to improve the results of cord blood transplants. Read more about this study
- Who is it for?
- Ages 1 month to 80 years
- Conditions the study is for
- Leukemia, Lymphocytic, Acute, Leukemia, Myelocytic, Acute, Leukemia, Myeloid, Chronic
- What is being tested?
- Expanded allogeneic cord blood (CB), One Unmanipulated and One Expanded Cord Blood Unit and Rituxan
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2003to Jul 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 1 month to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Disease-Specific Eligibility Requirements: Patients must have one of the following hematologic malignancies: 1. Acute Myelogenous Leukemia (AML), Myelodysplastic Syndrome (MDS) 2. Acute Lymphoblastic Leukemia (ALL) 3. Chronic Myelogenous Leukemia (CML) 4. Non-Hodgkin's Lymphoma (NHL) 5. Hodgkin's Disease (HD) 6. Chronic Lymphocytic Leukemia (CLL) 7. Chronic eosinophilic leukemia or Philadelphia chromosome negative CML.
- Greater than 1 month old and <=60 years old for full myeloablative therapy.
- Patients must have two CB units available which are matched with the patient at 4, 5, or 6/6 HLA class I (serological) and II (molecular) antigens. Each cord must contain at least 1E7 total nucleated cells/Kg recipient body weight in the pre-thawed fraction.
- Patient must be willing to undergo bone marrow harvest or peripheral blood progenitor cell (PBPC) collection for use in case of engraftment failure. If the patient is unable or fails to successfully undergo the collection, a family member must be identified to donate hematopoietic stem cells for haploidentical transplant in case of engraftment failure. If autologous hematopoietic stem cells cannot be procured due to marrow contamination by malignancy, or due to harvest failure, and a haploidentical relative is not available or not willing to donate, two cord blood units can be used as the back-up graft.
- Continuation to Criteria # 4: These units will be identified prior to enrollment in this study.
- Regimen 1 (Myeloablative mel/thiotepa/fludarabine): 1.Patients with ALL, HD, NHL, AML, MDS, CML, CLL and Chronic eosinophilic leukemia who are candidates for full myeloablative therapy. 2.Performance score of at least 60% by Karnofsky (age >= 12 years), or Lansky Play-Performance Scale (age <12 years). 3.Age >=1 month <=60 years (high-dose).
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- Continuation to Criteria # 6: 4.Adequate major organ system function as demonstrated by:a. Left ventricular ejection function of at least 40%. b.Pulmonary function test demonstrating a diffusion capacity of at least 50%. predicted (high-dose). c.Creatinine < 1.6 mg/dL. d.serum glutamate pyruvate transaminase (SGPT)/bilirubin <= to 2.0 x normal (high-dose).
- Eligibility for Regimen 2 (Non-myeloablative Cy-Flu-TBI): 1. Patients with ALL, AML, MDS, CML, NHL, CLL, Chronic eosinophilic leukemia and HD who are not candidates for full myeloablative therapy. All patients who received a prior autologous transplant are eligible. 2. Performance score of at least 60% by Karnofsky or PS < 3 (ECOG) (age >= 12 years), or Lansky Play-Performance Scale (age <12 years) 3. Age >= 1 month <=80 years
- Continuation to Criteria # 8: 4. Left ventricular ejection function of at least 30%; 5. Pulmonary function test demonstrating a diffusion capacity of at least 40% predicted; 6. Creatinine < 3.0 mg/dL; 7. SGPT <= to 4.0 x normal.
- Regimen 3 (Myeloablative VP16-TBI): 1. Patients with ALL who are candidates for myeloablative therapy, and require a TBI-containing regimen. 2. Performance score of at least 60% by Karnofsky or PS < 2 (ECOG) (age >= 12 years), or Lansky Play-Performance Scale (age <12 years). 3. Age >= 1 month <=50 years. 4. Organ function requirements: a. Left ventricular ejection function of at least 50%. b. Pulmonary function test demonstrating a diffusion capacity of at least 50% predicted. c. Creatinine < 1.6 mg/dL. d. SGPT <= 2.0 x normal.
Who cannot join
- HIV positive.
- Pregnancy.
- Serious medical Condition.
- Patients with signs \& symptoms leading to positive lumbar puncture (malignant cells in the CSF) or to documented metastatic parenchymal disease are ineligible for this study.
- Availability of appropriate, willing, HLA-matched related donor.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 770030
About this study
Official title: Randomized Trial of Unmanipulated Versus Expanded Cord Blood
The goal of this clinical research study is to learn if combining cord blood units to make the cells "take" faster in recipients will help to improve the results of cord blood transplants.
Read the detailed description
Cord blood is a source of blood forming cells that can be used for transplantation. The major problem with this type of transplant is the small number of blood forming cells available in each cord unit, which may delay the "take" of the graft in the recipient. Two strategies may be used to try to overcome this problem. One method is the combination of 2 units of cord blood and the other is the growing of the cord blood cells in the laboratory before they are transplanted in order to increase their number.
Participants will be randomly assigned (as in the toss of a coin) to one of two groups. If you are assigned to Study Arm 1, you will receive two cord blood units combined without growing the cells in the laboratory. If you are assigned to Study Arm 2, you will receive one cord blood unit combined with one cord blood unit which will be grown in the laboratory for two weeks before you receive it. Neither you nor your doctors will know in advance to which arm you will be assigned.
Placement of central venous catheter for collection of "back-up" stem cells:
Before you have back-up stem cell collected or you receive chemotherapy, you will require placement of a hollow plastic tube (catheter) into a large vein inside your body. This catheter will be used to draw blood and to give medications and fluids. The catheter is inserted through the skin in the upper chest and extends into the right side of your heart. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form for it.
Collection of back up stem cells:
Because collecting additional cells from the donor of the cord blood will not be possible if the transplant with cord blood fails, a back up blood or bone marrow sample will be collected from you and frozen before the high dose chemotherapy begins.
Peripheral blood progenitor cell collection (Leukapheresis):
Before collection of the blood stem cells, you will be treated with a drug called granulocyte colony stimulating factor (G-CSF), which will cause the important stem cells in the marrow to move the peripheral blood where they will be collected. This medication is given as a shot under the skin once a day for 3 - 7 days, at which time your blood stem cells will be collected from your central catheter during a 3-4 hour out-patient procedure. In some cases where a "good vein" cannot be accessed, a silicone venous catheter may be needed to collect your blood.
Bone Marrow Collection:
If the leukapheresis cannot be performed successfully, you will receive general anesthesia in the operating room and will have multiple needle sticks of the hip bones in order to collect bone marrow. Only a small part of your bone marrow (<5%) will be taken.
Selection of another donor as the alternate source of stem cells:
If your bone marrow or back-up blood stem cells cannot be collected, a family member whose bone marrow is the closest match will be chosen as the back up donor. The potential donor would have testing performed to assure that he/she is eligible to donate.
High-dose therapy:
Your bone marrow transplant doctors will give you one of four chemotherapy treatments, which are discussed below. If you have acute lymphoblastic leukemia, lymphoma, Hodgkin's disease, chronic lymphocytic leukemia, acute myelogenous leukemia, myelodysplastic syndrome, chronic eosinophilic leukemia or chronic myelogenous leukemia, are less than 61 years old, and can receive high-dose chemotherapy, you may be assigned to Treatment Regimen #1 - fludarabine-thiotepa-melphalan. Patients with ALL may be assigned to Treatment Regimen #1 or #3, depending on your doctor's evaluation, age and physical fitness.
You will receive melphalan as a single dose on Day -8, thiotepa as a single dose on Day -7, followed by fludarabine given once a day for 4 days in a row (Days -6 through -3. Rituximab may be given on Day -9 if appropriate for your disease. Day 0 is the day of transplantation, so the negative day numbers are used to label the treatment days before transplant.
If you have any of the diseases listed above, have had a bone marrow transplant in the past, or have a physical that makes you less likely to tolerate high-dose therapy well, you will be in the less aggressive Treatment Regimen #2, Fludarabine, Cyclophosphamide and low dose total body irradiation. The fludarabine will be given on Days -6, -5, -4, and -3. The cyclophosphamide will be given on Day -6. Irradiation will be given on day -1. Rituxan may be given on Day -7 if appropriate for your disease.
If you have acute lymphoblastic leukemia, are 50 years old or younger, and your doctors have decided that full-dose Total body irradiation is the best treatment for you, you will be assigned to Treatment Regimen #3 - total body irradiation-VP16. You will receive total body irradiation on Days -7,-6, -5 and -4, followed by VP16 (also known as etoposide) as a single dose on Day -3. Rituximab may be given on Day -8 if appropriate for your disease.
All chemotherapy, fluids and other medications that must be given by vein will be infused through your catheter. Once the backup stem cells are collected, all patients will be admitted to the hospital on Day -9 to begin receiving fluids. Chemotherapy may be stopped if intolerable side effects occur.
Expansion of expanded cord blood:
On Day -14, if you are in Treatment Group 2, one of your two cord blood units will be thawed and treated in the MD Anderson Stem Cell Laboratory with vitamin-like growth factors for 2 weeks before they are given back to you on day zero as described below. A small amount of cord blood cells (less than 3%) will be used for laboratory procedures that measure the quality of the product.
The CliniMACS System is a medical device that is used to separate types of blood cells from blood that is removed from the body during leukapheresis. These separated cells are processed for use in treatments such as stem cell transplants.
Transplantation of cord blood:
If you are in Treatment Group 1, two days following completion of high-dose therapy (Day 0), both units of cord blood will be thawed and infused (one at a time) through your catheter. Each unit will take about 30 minutes to infuse. Patients in Treatment Group 2 will receive one unit of cord blood that did not go through expansion of cells, followed by infusion of the unit that was grown in the laboratory for 14 days.
Graft versus host disease (GVHD) preventive therapy:
GVHD results from a reaction of the transplanted cord blood cells against certain tissues in your body. In an attempt to prevent or decrease the severity of GVHD, you will receive two drugs.
Mycophenolate mophetyl (MMF) pills will be given starting three days before your transplant, and will be continued until day 30 after the cord blood transplant. If you cannot take pills, the drug can be given through your catheter. If you develop GVHD, the use of MMF may be prolonged.
Tacrolimus will be given as a 24 hour continuous infusion over 3-6 weeks. Around Day 30 or 40 (after engraftment), the tacrolimus will be changed to pills given daily for 6-9 months. The number of tacrolimus pills may vary according to the blood levels of the drug, but usually are between 1 - 5. This medicine is used for 6-9 months (longer if chronic GVHD occurs).
You will remain on study as long as your disease does not return. If your disease returns, you will be taken off study and you may be offered participation in another study or be treated outside of this study.
Follow-up after transplant:
After you leave the hospital, you will be seen regularly in the Department of Blood and Marrow Transplantation at MD Anderson. The frequency of the visits may vary, but may be as often as daily. Blood (1-2 tablespoons) and urine tests will be performed. The frequency of blood tests may also vary, but may be performed daily. Patients will need a bone marrow sample collected before transplant and at 1 month, 3-4 months, and 5-7 months after transplant. After that, bone marrow samples will be collected once a year, indefinitely. To collect a bone marrow sample, an area of the hip or chest 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 scan of the thorax, abdomen, and pelvis performed before transplant and then at 1 month, 3-4 months, and 5-7 months after the transplant. After that it will be done yearly.
This is an investigational study. All treatment drugs are FDA approved and commercially available.
A total of 110 patients may take part in this study. All will be enrolled at MD Anderson.
- Conditions
- Leukemia, Lymphocytic, Acute, Leukemia, Myelocytic, Acute, Leukemia, Myeloid, Chronic, Lymphoma, Non-Hodgkin
- Being tested
- Expanded allogeneic cord blood (CB), One Unmanipulated and One Expanded Cord Blood Unit, Rituxan, Melphalan, Thiotepa
- Keywords
- ALL, Leukemia, Lymphocytic, Acute, AML, Leukemia, Myelocytic, Acute, CML, Leukemia, Myeloid, Chronic, NHL, Lymphoma, Non-Hodgkin, double cord blood transplant, expanded cord blood transplant, Rituxan, Rituximab, Melphalan, Alkeran, Thiotepa, Fludarabine, Fludarabine phosphate, Fludara, Cyclophosphamide, Cytoxan
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Expanded allogeneic cord blood (CB)Procedure or surgery
Also called double Cord blood transplant.
Transplantation of Two Unmanipulated Cord Blood Units.
One Unmanipulated and One Expanded Cord Blood UnitProcedure or surgery
Also called Expanded Cord Blood Transplant
Transplantation of One Unmanipulated and One Expanded Cord Blood Unit.
RituxanDrug
Also called Rituximab
375 mg/m2 by vein on Day - 9 for patients with CD20 + malignancies.
MelphalanDrug
Also called Alkeran
140 mg/m2 by vein on Day -8.
ThiotepaDrug
5 mg/Kg by vein on Day -7.
FludarabineDrug
Also called Fludarabine Phosphate, Fludara
40 mg/m2 by vein on Days -6 to -3.
CyclophosphamideDrug
Also called Cytoxan, Neosar
50 mg/kg by vein on Day -6.
MesnaDrug
Also called Mesnex
10 mg/kg by vein before the 1st dose of Cyclophosphamide, then 10 mg/kg every 4 hours for four more doses (total of 50 mg/Kg).
Total body irradiation (TBI)Radiation
Also called TBI, XRT
Total body irradiation (TBI) given on Day -1 at 2 Gy.
| Study group | Role | What they receive |
|---|---|---|
| Double Cord Blood Transplant Group | Experimental | Two Unmanipulated Cord Blood units. Rituxan 375 mg/m2 by vein for patients with CD20 + malignancies. Melphalan 140 mg/m2 by vein on Day -8. Thiotepa 5 mg/Kg by vein on Day -7. Fludarabine 40 mg/m2 by vein on Days -6 to -3. Receives: Procedure: Expanded allogeneic cord blood (CB); Drug: Rituxan; Drug: Melphalan; Drug: Thiotepa; Drug: Fludarabine |
| One Expanded Cord Blood Transplant Group | Experimental | One Unmanipulated and One Expanded Cord Blood Unit. Fludarabine 40 mg/m2 by vein on Days -6 to -3. Cyclophosphamide 50 mg/kg by vein on Day -6. Mesna 10 mg/kg by vein before the 1st dose of Cyclophosphamide, then 10 mg/kg every 4 hours for four more doses (total of 50 mg/Kg). Total body irradiation (TBI) given on Day -1 at 2 Gy. Receives: Procedure: One Unmanipulated and One Expanded Cord Blood Unit; Drug: Rituxan; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Mesna; Radiation: Total body irradiation (TBI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time To Neutrophil Engraftment
Engraftment is defined as a sustained ANC > 0.5 x 10^9/L for at least 3 consecutive days. Engraftment date is the first of the 3 days with sustained absolute neutrophil count (ANC) >/= 0.5 x 10^9/L.
Measured: First 100 days, evaluation and blood tests twice weekly
Number of Participants With Engraftment
Engraftment defined as a sustained absolute neutrophil count (ANC) > 0.5 x 10^9/L for at least 3 consecutive days. Engraftment Failure defined as ANC <500/ul by day +42 and participant has no evidence of donor chimerism on bone marrow examination.
Measured: First 100 days, evaluation and blood tests twice weekly
Secondary outcomes (3)
Rate of Acute Graft Versus Host Disease (GVHD)
Number of participants who display features of acute GVHD within 100 days of transplant.
Measured: Review over first 100 days
Rate of Chronic GVHD
Number of participants who present GVHD post-transplant and display features of chronic GVHD. Diagnostic and distinctive features of chronic GVHD are present. There are no features of acute GVHD.
Measured: Up to one year
Number of Participants Severity of Acute GVHD by Treatment Arm
The severity of acute GVHD is determined by an assessment of the degree of involvement of the skin, liver, and gastrointestinal tract. The stages of individual organ involvement is assessed using Glucksberg grade (I-IV) where Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.
Measured: Following first 100 days, up to one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2003 (estimated)
- Study startApr 2003
- Primary completionJul 2016
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Leukemia, Lymphocytic, AcuteStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Cellgenix
- Responsible party
- Sponsor
- Investigators
- Simrit Parmar, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00067002
- Sponsor's protocol ID
- ID02-407
- Other IDs
- CA061508, NCI-2012-01299
- Status last verified
- Apr 2019
- First submitted
- 8 Aug 2003
- Last updated
- 1 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial of Unmanipulated Versus Expanded Cord Blood
- ClinicalTrials.gov ID
- NCT00067002
- Acronym / sponsor ID
- ID02-407
- Conditions
- Leukemia, Lymphocytic, Acute, Leukemia, Myelocytic, Acute, Leukemia, Myeloid, Chronic, Lymphoma, Non-Hodgkin
- Keywords
- ALL, Leukemia, Lymphocytic, Acute, AML, Leukemia, Myelocytic, Acute, CML, Leukemia, Myeloid, Chronic, NHL, Lymphoma, Non-Hodgkin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 110 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Cellgenix
- Study start
- Apr 2003
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 11 Aug 2003 (estimated)
- Results
- Posted 1 May 2019
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 combining cord blood units to make the cells "take" faster in recipients will help to improve the results of cord blood transplants.
Detailed description
Cord blood is a source of blood forming cells that can be used for transplantation. The major problem with this type of transplant is the small number of blood forming cells available in each cord unit, which may delay the "take" of the graft in the recipient. Two strategies may be used to try to overcome this problem. One method is the combination of 2 units of cord blood and the other is the growing of the cord blood cells in the laboratory before they are transplanted in order to increase their number.
Participants will be randomly assigned (as in the toss of a coin) to one of two groups. If you are assigned to Study Arm 1, you will receive two cord blood units combined without growing the cells in the laboratory. If you are assigned to Study Arm 2, you will receive one cord blood unit combined with one cord blood unit which will be grown in the laboratory for two weeks before you receive it. Neither you nor your doctors will know in advance to which arm you will be assigned.
Placement of central venous catheter for collection of "back-up" stem cells:
Before you have back-up stem cell collected or you receive chemotherapy, you will require placement of a hollow plastic tube (catheter) into a large vein inside your body. This catheter will be used to draw blood and to give medications and fluids. The catheter is inserted through the skin in the upper chest and extends into the right side of your heart. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form for it.
Collection of back up stem cells:
Because collecting additional cells from the donor of the cord blood will not be possible if the transplant with cord blood fails, a back up blood or bone marrow sample will be collected from you and frozen before the high dose chemotherapy begins.
Peripheral blood progenitor cell collection (Leukapheresis):
Before collection of the blood stem cells, you will be treated with a drug called granulocyte colony stimulating factor (G-CSF), which will cause the important stem cells in the marrow to move the peripheral blood where they will be collected. This medication is given as a shot under the skin once a day for 3 - 7 days, at which time your blood stem cells will be collected from your central catheter during a 3-4 hour out-patient procedure. In some cases where a "good vein" cannot be accessed, a silicone venous catheter may be needed to collect your blood.
Bone Marrow Collection:
If the leukapheresis cannot be performed successfully, you will receive general anesthesia in the operating room and will have multiple needle sticks of the hip bones in order to collect bone marrow. Only a small part of your bone marrow (<5%) will be taken.
Selection of another donor as the alternate source of stem cells:
If your bone marrow or back-up blood stem cells cannot be collected, a family member whose bone marrow is the closest match will be chosen as the back up donor. The potential donor would have testing performed to assure that he/she is eligible to donate.
High-dose therapy:
Your bone marrow transplant doctors will give you one of four chemotherapy treatments, which are discussed below. If you have acute lymphoblastic leukemia, lymphoma, Hodgkin's disease, chronic lymphocytic leukemia, acute myelogenous leukemia, myelodysplastic syndrome, chronic eosinophilic leukemia or chronic myelogenous leukemia, are less than 61 years old, and can receive high-dose chemotherapy, you may be assigned to Treatment Regimen #1 - fludarabine-thiotepa-melphalan. Patients with ALL may be assigned to Treatment Regimen #1 or #3, depending on your doctor's evaluation, age and physical fitness.
You will receive melphalan as a single dose on Day -8, thiotepa as a single dose on Day -7, followed by fludarabine given once a day for 4 days in a row (Days -6 through -3. Rituximab may be given on Day -9 if appropriate for your disease. Day 0 is the day of transplantation, so the negative day numbers are used to label the treatment days before transplant.
If you have any of the diseases listed above, have had a bone marrow transplant in the past, or have a physical that makes you less likely to tolerate high-dose therapy well, you will be in the less aggressive Treatment Regimen #2, Fludarabine, Cyclophosphamide and low dose total body irradiation. The fludarabine will be given on Days -6, -5, -4, and -3. The cyclophosphamide will be given on Day -6. Irradiation will be given on day -1. Rituxan may be given on Day -7 if appropriate for your disease.
If you have acute lymphoblastic leukemia, are 50 years old or younger, and your doctors have decided that full-dose Total body irradiation is the best treatment for you, you will be assigned to Treatment Regimen #3 - total body irradiation-VP16. You will receive total body irradiation on Days -7,-6, -5 and -4, followed by VP16 (also known as etoposide) as a single dose on Day -3. Rituximab may be given on Day -8 if appropriate for your disease.
All chemotherapy, fluids and other medications that must be given by vein will be infused through your catheter. Once the backup stem cells are collected, all patients will be admitted to the hospital on Day -9 to begin receiving fluids. Chemotherapy may be stopped if intolerable side effects occur.
Expansion of expanded cord blood:
On Day -14, if you are in Treatment Group 2, one of your two cord blood units will be thawed and treated in the MD Anderson Stem Cell Laboratory with vitamin-like growth factors for 2 weeks before they are given back to you on day zero as described below. A small amount of cord blood cells (less than 3%) will be used for laboratory procedures that measure the quality of the product.
The CliniMACS System is a medical device that is used to separate types of blood cells from blood that is removed from the body during leukapheresis. These separated cells are processed for use in treatments such as stem cell transplants.
Transplantation of cord blood:
If you are in Treatment Group 1, two days following completion of high-dose therapy (Day 0), both units of cord blood will be thawed and infused (one at a time) through your catheter. Each unit will take about 30 minutes to infuse. Patients in Treatment Group 2 will receive one unit of cord blood that did not go through expansion of cells, followed by infusion of the unit that was grown in the laboratory for 14 days.
Graft versus host disease (GVHD) preventive therapy:
GVHD results from a reaction of the transplanted cord blood cells against certain tissues in your body. In an attempt to prevent or decrease the severity of GVHD, you will receive two drugs.
Mycophenolate mophetyl (MMF) pills will be given starting three days before your transplant, and will be continued until day 30 after the cord blood transplant. If you cannot take pills, the drug can be given through your catheter. If you develop GVHD, the use of MMF may be prolonged.
Tacrolimus will be given as a 24 hour continuous infusion over 3-6 weeks. Around Day 30 or 40 (after engraftment), the tacrolimus will be changed to pills given daily for 6-9 months. The number of tacrolimus pills may vary according to the blood levels of the drug, but usually are between 1 - 5. This medicine is used for 6-9 months (longer if chronic GVHD occurs).
You will remain on study as long as your disease does not return. If your disease returns, you will be taken off study and you may be offered participation in another study or be treated outside of this study.
Follow-up after transplant:
After you leave the hospital, you will be seen regularly in the Department of Blood and Marrow Transplantation at MD Anderson. The frequency of the visits may vary, but may be as often as daily. Blood (1-2 tablespoons) and urine tests will be performed. The frequency of blood tests may also vary, but may be performed daily. Patients will need a bone marrow sample collected before transplant and at 1 month, 3-4 months, and 5-7 months after transplant. After that, bone marrow samples will be collected once a year, indefinitely. To collect a bone marrow sample, an area of the hip or chest 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 scan of the thorax, abdomen, and pelvis performed before transplant and then at 1 month, 3-4 months, and 5-7 months after the transplant. After that it will be done yearly.
This is an investigational study. All treatment drugs are FDA approved and commercially available.
A total of 110 patients may take part in this study. All will be enrolled at MD Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Double Cord Blood Transplant Group | Experimental | Procedure: Expanded allogeneic cord blood (CB), Drug: Rituxan, Drug: Melphalan, Drug: Thiotepa, Drug: FludarabineTwo Unmanipulated Cord Blood units. Rituxan 375 mg/m2 by vein for patients with CD20 + malignancies. Melphalan 140 mg/m2 by vein on Day -8. Thiotepa 5 mg/Kg by vein on Day -7. Fludarabine 40 mg/m2 by vein on Days -6 to -3. |
| One Expanded Cord Blood Transplant Group | Experimental | Procedure: One Unmanipulated and One Expanded Cord Blood Unit, Drug: Rituxan, Drug: Fludarabine, Drug: Cyclophosphamide, Drug: Mesna, Radiation: Total body irradiation (TBI)One Unmanipulated and One Expanded Cord Blood Unit. Fludarabine 40 mg/m2 by vein on Days -6 to -3. Cyclophosphamide 50 mg/kg by vein on Day -6. Mesna 10 mg/kg by vein before the 1st dose of Cyclophosphamide, then 10 mg/kg every 4 hours for four more doses (total of 50 mg/Kg). Total body irradiation (TBI) given on Day -1 at 2 Gy. |
Who may qualify
- Ages
- 1 month to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Disease-Specific Eligibility Requirements: Patients must have one of the following hematologic malignancies: 1. Acute Myelogenous Leukemia (AML), Myelodysplastic Syndrome (MDS) 2. Acute Lymphoblastic Leukemia (ALL) 3. Chronic Myelogenous Leukemia (CML) 4. Non-Hodgkin's Lymphoma (NHL) 5. Hodgkin's Disease (HD) 6. Chronic Lymphocytic Leukemia (CLL) 7. Chronic eosinophilic leukemia or Philadelphia chromosome negative CML.
- Greater than 1 month old and <=60 years old for full myeloablative therapy.
- Patients must have two CB units available which are matched with the patient at 4, 5, or 6/6 HLA class I (serological) and II (molecular) antigens. Each cord must contain at least 1E7 total nucleated cells/Kg recipient body weight in the pre-thawed fraction.
- Patient must be willing to undergo bone marrow harvest or peripheral blood progenitor cell (PBPC) collection for use in case of engraftment failure. If the patient is unable or fails to successfully undergo the collection, a family member must be identified to donate hematopoietic stem cells for haploidentical transplant in case of engraftment failure. If autologous hematopoietic stem cells cannot be procured due to marrow contamination by malignancy, or due to harvest failure, and a haploidentical relative is not available or not willing to donate, two cord blood units can be used as the back-up graft.
- Continuation to Criteria # 4: These units will be identified prior to enrollment in this study.
Key exclusion criteria (5 listed)
- HIV positive.
- Pregnancy.
- Serious medical Condition.
- Patients with signs \& symptoms leading to positive lumbar puncture (malignant cells in the CSF) or to documented metastatic parenchymal disease are ineligible for this study.
- Availability of appropriate, willing, HLA-matched related donor.
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 |
|---|---|---|
| Expanded allogeneic cord blood (CB)Also: double Cord blood transplant.Transplantation of Two Unmanipulated Cord Blood Units. | Procedure or surgery | Double Cord Blood Transplant Group |
| One Unmanipulated and One Expanded Cord Blood UnitAlso: Expanded Cord Blood TransplantTransplantation of One Unmanipulated and One Expanded Cord Blood Unit. | Procedure or surgery | One Expanded Cord Blood Transplant Group |
| RituxanAlso: Rituximab375 mg/m2 by vein on Day - 9 for patients with CD20 + malignancies. | Drug | Double Cord Blood Transplant Group, One Expanded Cord Blood Transplant Group |
| MelphalanAlso: Alkeran140 mg/m2 by vein on Day -8. | Drug | Double Cord Blood Transplant Group |
| Thiotepa5 mg/Kg by vein on Day -7. | Drug | Double Cord Blood Transplant Group |
| FludarabineAlso: Fludarabine Phosphate, Fludara40 mg/m2 by vein on Days -6 to -3. | Drug | Double Cord Blood Transplant Group, One Expanded Cord Blood Transplant Group |
| CyclophosphamideAlso: Cytoxan, Neosar50 mg/kg by vein on Day -6. | Drug | One Expanded Cord Blood Transplant Group |
| MesnaAlso: Mesnex10 mg/kg by vein before the 1st dose of Cyclophosphamide, then 10 mg/kg every 4 hours for four more doses (total of 50 mg/Kg). | Drug | One Expanded Cord Blood Transplant Group |
| Total body irradiation (TBI)Also: TBI, XRTTotal body irradiation (TBI) given on Day -1 at 2 Gy. | Radiation | One Expanded Cord Blood Transplant Group |
Primary outcome
Time To Neutrophil Engraftment
Time frame: First 100 days, evaluation and blood tests twice weekly
Engraftment is defined as a sustained ANC > 0.5 x 10^9/L for at least 3 consecutive days. Engraftment date is the first of the 3 days with sustained absolute neutrophil count (ANC) >/= 0.5 x 10^9/L.
Number of Participants With Engraftment
Time frame: First 100 days, evaluation and blood tests twice weekly
Engraftment defined as a sustained absolute neutrophil count (ANC) > 0.5 x 10^9/L for at least 3 consecutive days. Engraftment Failure defined as ANC <500/ul by day +42 and participant has no evidence of donor chimerism on bone marrow examination.
3 secondary outcomes
Rate of Acute Graft Versus Host Disease (GVHD)
Time frame: Review over first 100 days
Rate of Chronic GVHD
Time frame: Up to one year
Number of Participants Severity of Acute GVHD by Treatment Arm
Time frame: Following first 100 days, up to one year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- University of Texas 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.
Simrit Parmar, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Expanded allogeneic cord blood (CB), One Unmanipulated and One Expanded Cord Blood Unit and Rituxan in people with Leukemia, Lymphocytic, Acute and Leukemia, Myelocytic, Acute, run by M.D. Anderson Cancer Center at 1 site in United States.
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 10 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: finished, as of the sponsor's last update on 1 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Time To Neutrophil Engraftment (time frame: First 100 days, evaluation and blood tests twice weekly). The study lists 2 primary outcomes in all. 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 1 May 2019.