Stem Cell TransplantationPhase 2NCT00857389
Thiotepa-Clofarabine-Busulfan With Allogeneic Stem Cell Transplant for High Risk Malignancies
A Phase 2 study testing Thiotepa, Clofarabine and Busulfan in people with Stem Cell Transplantation and Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential participant. The goal of this clinical research study is to learn if thiotepa, busulfan, and clofarabine, when given before an allogeneic (bone marrow , blood, or cord blood cells) or haploidentical (bone marrow) stem cell… Read more about this study
- Who is it for?
- Ages Up to 60 years
- Conditions the study is for
- Stem Cell Transplantation, Leukemia, Lymphoma
- What is being tested?
- Thiotepa, Clofarabine and Busulfan
- 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
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Mar 2009to 9 Mar 2019
- 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 Up to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosed with one of the following diseases:
- Acute myelogenous leukemia (AML) in induction failure, relapse, past first remission, or CR1 considered at risk for relapse
- Myelodysplastic syndromes with International Prognostic Scoring System score (IPSS score) >/= 2 or myelodysplasia that has not responded to chemotherapy
- Biphenotypic leukemia
- Acute lymphocytic leukemia with induction failure, first complete remission with high risk cytogenetics (e.g. Philadelphia positive chromosome, t(4:11) Remission requiring more than 2 chemotherapy to achieve remission, or any stage beyond CR1
- Chronic Myelogenous Leukemia (CML): second chronic phase, accelerated phase or blast crises with less than 10% blasts in the bone marrow, or CR1 and resistance to Gleevec or other tyrosine kinase inhibitors
Show all 18Show fewer
- Non-Hodgkin's Lymphoma - induction failures, second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant)
- Hodgkin's disease - induction failure, second or later complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant).
- Chronic Lymphocytic Leukemia that has failed induction therapy or Rai Stages 2-4
- Related or unrelated donor which is HLA-matched or mismatched in 1 HLA A, B, C, DR, or DQ locus is acceptable (i.e. >/= 9/10 matched related or unrelated donor, matched with molecular high-resolution technique per current std. for BMT program). Cord blood units must match patient at 4, 5, or 6/6 HLA class 1 serological \& II molecular antigens with a min. of 2 x 10e7 TNC/kg recipient weight in the pre-thawed fraction. For patient lacking a matched related or unrelated donor or acceptable cord blood unit(s), a related haploidentical donor (</= 7/8 allele matched at A, B, C, DR loci) may be used.
- Age </= 60 years.
- Lansky performance score >/= 50% for patients </= 16 years of age, or Zubrod performance status score of 0-2 for patients > 16 years of age.
- Cardiac function - left ventricular ejection fraction >/= 40%.
- Pulmonary function - diffusion capacity of at least 50% predicted. Children unable to perform pulmonary function tests (e.g. less than 7 years old) pulse oximetry of >/= 92% on room air.
- Serum creatinine < 1.6 mg/dL or creatinine clearance >/= 50 ml/min.
- SGPT </= 200 IU/mL, serum bilirubin < 1.5 x normal.
- Written informed consent and assent as is age appropriate.
- No active infection.
Who cannot join
- Pregnancy in women of child bearing potential (pregnancy test performed within 2 weeks of study entry).
- HIV positive (highly immunosuppressive treatment)
- Active CNS leukemia
- Chronic or active Hepatitis B or Hepatitis C. If questions about liver health discuss with PI and strongly consider liver biopsy.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential participant.
The goal of this clinical research study is to learn if thiotepa, busulfan, and clofarabine, when given before an allogeneic (bone marrow , blood, or cord blood cells) or haploidentical (bone marrow) stem cell transplantation can help to control cancers of the bone marrow and lymph node system. The safety of this treatment will also be studied.
Read more
This is an investigational study. Thiotepa and clofarabine are FDA approved and commercially available for the treatment of leukemia. Busulfan is FDA approved and commercially available for use in stem cell transplantation. The combination of thiotepa, clofarabine, and busulfan together with a stem cell transplant is investigational.
Up to 60 participants will take part in this study. All will be enrolled at M. D. Anderson.
Read the detailed description
The Study Drugs:
Thiotepa and busulfan are designed to bind to DNA (genetic material of cells), which may cause cancer cells to die. They are commonly used in stem cell transplants.
Clofarabine is designed to interfere with the growth and development of cancer cells.
Study Drug Administration:
If you are found to be eligible to take part in this study, you will begin receiving the study drugs before you receive the stem cell transplant.
The days before you receive your stem cells are called minus days, such as Day -2 and Day -1. The day you receive the stem cells is called Day 0. The days after you receive the stem cells are called plus days, such as Day +1 and Day +2.
On Day -8 (8 days before you receive the stem cell transplant), you will receive thiotepa through a central venous catheter (CVC) over 2 hours. A CVC is a sterile, flexible tube that will be placed into a large vein while you are under local anesthesia. 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.
On Day -7, you will receive busulfan through a CVC. This dose of busulfan is a low level "test" dose to check how your blood levels change over time. This information will be used to decide the next dose level of busulfan.
Blood (about 1 teaspoon each time) will be drawn 6-11 times total over Days -7 and -5 for pharmacokinetic (PK) testing. PK testing measures the amount of busulfan in the body at different time points. This PK testing will be done to find the dose of busulfan needed for your body size on the other days that you receive busulfan. A heparin lock line will be placed in a vein to lower the number of needed sticks performed for draws. If you cannot have the blood level tests performed for any reason, you will receive the standard busulfan dose.
On Days -6, -5, -4, and -3, you will receive clofarabine through a CVC over 1 hour.
On Days -5, -4, and -3, you will receive busulfan through a CVC over 3 hours.
If you will receive stem cells from a donor whose cells do not match your own cells closely, on Days -4 and -3 you will also receive antithymocyte globulin (ATG) by vein over 4 hours. This will help to reduce the risk of your body rejecting the transplant. If your transplant will involve haploidentical stem cells, you will not receive ATG on Days -4 and -3.
On Days -2 and -1, you will "rest," which means you will not be given any drugs, but your CVC will remain in place.
If thiotepa is not available:
If thiotepa is not available, or if you doctor thinks it is in your best interest, you will receive the following study drugs and total body irradiation (TBI) before you receive the stem cell transplant. TBI involves the delivery of high doses of radiation designed to destroy cancer cells and/or lower the immune system in order to lower the risk of the body rejecting the new stem cells.
Between Days -16 and -7, you will receive a low-level "test" dose of busulfan by vein over about 45 minutes to 1 hour. Test doses are used to study how your body breaks down busulfan and decide the dose of busulfan that you will receive. You may receive the test dose before Day -6 as an outpatient in the clinic, or on Day -6 as an inpatient in the hospital.
Blood (about 1 teaspoon each time) will then be drawn for PK testing up to 11 times over the 11 hours after the busulfan test dose and on Day -4. PK testing measures the amount of study drug in the body at different time points. The study staff will tell you more about the PK testing schedule.
A heparin lock line will be placed in your vein before the PK testing to lower the number of needle sticks needed for these draws. If for any reason it is not possible for the PK tests to be performed, you will receive the standard dose of busulfan.
On Day -7 or Day -6, you will be admitted to the hospital and given fluids through a CVC to hydrate you.
On Days -5, -4, -3, and -2, you will receive clofarabine through a CVC over 1 hour.
On Days -4, -3, and -2, you will receive busulfan through a CVC over 3 hours.
If you will receive stem cells from a donor whose cells do not match your own cells closely, on Days -3 and -2 you will also receive antithymocyte globulin (ATG) by vein over 4 hours. This will help to reduce the risk of your body rejecting the transplant. If your transplant will involve haploidentical stem cells, you will not receive ATG on Days -3 and -2.
On Day -1, you will receive TBI one time.
Stem Cell Transplant:
On Day 0, you will have an allogeneic or haploidentical stem cell transplant through the CVC. Allogeneic stem cells come from a donor whose cells closely match your own cells. Haploidentical stem cells come from a donor whose cells do not match your own cells as closely, but they are specially processed to help prevent graft versus host disease (GVHD).
Receiving stem cells is similar to receiving a blood transfusion. The time required to receive the stem cells will depend on the type of cells you are receiving. Receiving cord blood stem cells can take several minutes. Receiving bone marrow and blood stem cells may take several hours.
You will receive G-CSF (filgrastim) (which helps to produce white blood cells) as an injection under the skin once a day, starting 1 week after the transplant, until your blood cell levels return to normal.
You will receive drugs (mycophenolate mofetil (MMF), tacrolimus and/or methotrexate) to help prevent side effects, such as GVHD. You will receive methylprednisolone if you develop GVHD.
You will stay in the hospital for about 4 weeks after the stem cell transplantation.
If you had a haploidentical stem cell transplant, on Days 3 and 4 after your stem cell transplant, you will receive cyclophosphamide through a CVC over 3 hours. Mesna will be given by vein at the same time you are given each dose of cyclophosphamide, to help protect your bladder from bleeding.
Study Visits:
Beginning on Day -9, once a day while you are in the hospital:
- You will have a physical exam, including measurements of your vital signs.
- You will be asked if you have had any side effects.
- Blood (about 4 tablespoons) will be drawn to test your blood cell counts. Two (2) times a week, this blood will be also be used for routine tests.
After you are out of the hospital, 2 times a month until it has been 100 days after the transplant:
- You will have a physical exam, including measurements of your vital signs and weight.
- You will be asked if you have had any side effects.
- Blood (about 4 tablespoons) will be drawn for routine tests.
About 1, 3, 6, and 12 months after the transplant, blood (about 4 tablespoons) will be drawn to check the status of the disease. You will also have bone marrow aspirations to check the status of the disease. You will also have a physical exam.
If the doctor thinks it is necessary, you may have extra tests and procedures.
Length of Study:
You will be on study for about 1 year. You will be taken off study if the disease gets worse or needs further treatment.
Follow-Up:
If you live close to M. D. Anderson, you will return to the clinical once every several months for a physical exam. At these visits, blood (about 3 teaspoons) will be drawn for routine tests.
You and/or your local doctor will be called every several months and asked about your health status and if the leukemia or MDS has come back.
- Conditions
- Stem Cell Transplantation, Leukemia, Lymphoma
- Being tested
- Thiotepa, Clofarabine, Busulfan, Allogeneic Stem Cell Transplantation, Thymoglobulin (ATG)
- Keywords
- Cancer, Blood And Marrow Transplantation, Stem Cell, Leukemia, Lymphoma, Pediatrics, Bone marrow, Lymph node system, Allogeneic Stem Cell Transplant, ASCT, Busulfan, Busulfex, Myleran, Clofarabine, Clofarex, Clolar, Thiotepa, Antithymocyte globulin, ATG, Thymoglobulin
- Medical subject headings
- Leukemia, Lymphoma, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ThiotepaDrug
Also called Thio
5 mg/kg through a central venous catheter (CVC) over 2 hours on Day -8.
ClofarabineDrug
Also called Clo, Clofarex, Clolar
40 mg/m^2 through a central venous catheter (CVC) over 1 hour daily on 4 consecutive days (Days -6 through -3).
BusulfanDrug
Also called Busulfex, Myleran
Test dose of 0.5 mg/kg through a central venous catheter (CVC)over 30 minutes on Day -7.
High dose 5,000 µMol-min through a central venous catheter (CVC) over 3 hours on Days -5, -4, and -3.
Allogeneic Stem Cell TransplantationProcedure or surgery
Also called ASCT, SCT
Infusion of stem cells through through a central venous catheter (CVC) On Day 0.
Thymoglobulin (ATG)Drug
Also called Antithymocyte globulin
1.25 mg/kg by vein on Day -4 and 1.75 mg/kg on Day -3.
G-CSF (Filgrastim)Drug
Also called Neupogen
5 µg/kg Injection under the skin once a day, starting 1 week after transplant, until blood cell levels return to normal.
TacrolimusDrug
Also called Prograf
Starting dose of 0.015 mg/kg (ideal body weight) as a 24 hour continuous infusion daily, to be changed to oral dosing when tolerated. Tacrolimus is to be tapered as indicated after transplant day 90, if no GVHD is present. Tacrolimus is adjusted trough level of 5-15 ng/mL.
MethotrexateDrug
5 mg/m2 by vein on Days 1, 3 and 6 and Day +11 post transplant. The Day 11 methotrexate dose may be held as indicated if mucositis is present.
CyclophosphamideDrug
Also called Cytoxan, Neosar
Post haploidentical stem cell transplant participants: 50 mg/kg by vein on Days + 3 and + 4.
MesnaDrug
Also called Mesnex
Post haploidentical stem cell transplant participants: 10 mg/kg by vein just prior to the first dose of cyclophosphamide, repeated every 4 hours for a total of ten (10) doses.
| Study group | Role | What they receive |
|---|---|---|
| Thio-Clo-Bu with Allo SCT | Experimental | Pre-transplant conditioning regimen:
Thiotepa (Thio) + Clofarabine (Clo) + Busulfan (Blu) + Allogeneic Stem Cell Transplantation (Allo SCT) + ATG + G-CSF
Post haploidentical stem cell transplant participants:
Cyclophosphamide 50 mg/kg by vein on Days + 3 and + 4. Mesna 10 mg/kg by vein just prior to the first dose of cyclophosphamide, repeated every 4 hours for a total of ten (10) doses. Receives: Drug: Thiotepa; Drug: Clofarabine; Drug: Busulfan; Procedure: Allogeneic Stem Cell Transplantation; Drug: Thymoglobulin (ATG); Drug: G-CSF (Filgrastim); Drug: Tacrolimus; Drug: Methotrexate; Drug: Cyclophosphamide; Drug: Mesna |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Survival Rate at 100 Days Post-transplant
The toxicities will be monitored and scored on a daily basis following the methods of Simon R. Practical Bayesian Guideline for Phase IIB Clinical Trials. A Bayesian stopping rule will be used to stop the trial if there is a 90% chance that the true toxicity rate exceeds the target toxicity rate of 0.25.
Measured: 100 days post-transplant
Secondary outcomes (6)
Number of Participants With Disease Free Survival
Kaplan-Meier product limit method to estimate the disease free survival.
Measured: Up to 2 years post transplant
Overall Survival Rate
Overall Survival Rate will be estimated using the Kaplan-Meier method.
Measured: Up to 3 years post transplant
Graft vs Host Disease (GVHD)
Severity of toxicities graded according to the NCI Common Toxicity Criteria Adverse Effects (CTCAE) v3.0. Standard reporting guidelines followed for adverse events. Safety data summarized by category, severity and frequency.
Measured: Up to 30 days post transplant
Engraftment
Engraftment is most commonly defined as the first of three consecutive days of achieving a sustained peripheral blood neutrophil count of >500 × 10^6/L .
Measured: up to 100 days post transplant
Number of Participants With Serious Adverse Events
Severity of toxicities graded according to the NCI Common Toxicity Criteria Adverse Effects (CTCAE) v3.0. Standard reporting guidelines followed for adverse events. Safety data summarized by category, severity and frequency.
Measured: up to 30 days post transplant
Relapse Rate of Participants Treated With Thiotepa, Busulfan, and Clofarabine
Relapse Rate will be estimated using the Kaplan-Meier method.
Measured: Up to 2 years post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2009 (estimated)
- Study start2 Mar 2009
- Primary completion9 Mar 2019
- Study completion9 Mar 2019
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 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kris M. Mahadeo, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00857389
- Sponsor's protocol ID
- 2008-0363
- Other IDs
- NCI-2012-01630
- Status last verified
- Mar 2020
- First submitted
- 5 Mar 2009
- Last updated
- 7 Apr 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Thiotepa-Clofarabine-Busulfan With Allogeneic Stem Cell Transplant for High Risk Malignancies
- ClinicalTrials.gov ID
- NCT00857389
- Acronym / sponsor ID
- 2008-0363
- Conditions
- Stem Cell Transplantation, Leukemia, Lymphoma
- Keywords
- Cancer, Blood And Marrow Transplantation, Stem Cell, Leukemia, Lymphoma, Pediatrics, Bone marrow, Lymph node system
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- 2 Mar 2009 (actual)
- Primary completion
- 9 Mar 2019 (actual)
- Study completion
- 9 Mar 2019 (actual)
- First posted
- 6 Mar 2009 (estimated)
- Results
- Posted 7 Apr 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential participant.
The goal of this clinical research study is to learn if thiotepa, busulfan, and clofarabine, when given before an allogeneic (bone marrow , blood, or cord blood cells) or haploidentical (bone marrow) stem cell transplantation can help to control cancers of the bone marrow and lymph node system. The safety of this treatment will also be studied.
This is an investigational study. Thiotepa and clofarabine are FDA approved and commercially available for the treatment of leukemia. Busulfan is FDA approved and commercially available for use in stem cell transplantation. The combination of thiotepa, clofarabine, and busulfan together with a stem cell transplant is investigational.
Up to 60 participants will take part in this study. All will be enrolled at M. D. Anderson.
Detailed description
The Study Drugs:
Thiotepa and busulfan are designed to bind to DNA (genetic material of cells), which may cause cancer cells to die. They are commonly used in stem cell transplants.
Clofarabine is designed to interfere with the growth and development of cancer cells.
Study Drug Administration:
If you are found to be eligible to take part in this study, you will begin receiving the study drugs before you receive the stem cell transplant.
The days before you receive your stem cells are called minus days, such as Day -2 and Day -1. The day you receive the stem cells is called Day 0. The days after you receive the stem cells are called plus days, such as Day +1 and Day +2.
On Day -8 (8 days before you receive the stem cell transplant), you will receive thiotepa through a central venous catheter (CVC) over 2 hours. A CVC is a sterile, flexible tube that will be placed into a large vein while you are under local anesthesia. 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.
On Day -7, you will receive busulfan through a CVC. This dose of busulfan is a low level "test" dose to check how your blood levels change over time. This information will be used to decide the next dose level of busulfan.
Blood (about 1 teaspoon each time) will be drawn 6-11 times total over Days -7 and -5 for pharmacokinetic (PK) testing. PK testing measures the amount of busulfan in the body at different time points. This PK testing will be done to find the dose of busulfan needed for your body size on the other days that you receive busulfan. A heparin lock line will be placed in a vein to lower the number of needed sticks performed for draws. If you cannot have the blood level tests performed for any reason, you will receive the standard busulfan dose.
On Days -6, -5, -4, and -3, you will receive clofarabine through a CVC over 1 hour.
On Days -5, -4, and -3, you will receive busulfan through a CVC over 3 hours.
If you will receive stem cells from a donor whose cells do not match your own cells closely, on Days -4 and -3 you will also receive antithymocyte globulin (ATG) by vein over 4 hours. This will help to reduce the risk of your body rejecting the transplant. If your transplant will involve haploidentical stem cells, you will not receive ATG on Days -4 and -3.
On Days -2 and -1, you will "rest," which means you will not be given any drugs, but your CVC will remain in place.
If thiotepa is not available:
If thiotepa is not available, or if you doctor thinks it is in your best interest, you will receive the following study drugs and total body irradiation (TBI) before you receive the stem cell transplant. TBI involves the delivery of high doses of radiation designed to destroy cancer cells and/or lower the immune system in order to lower the risk of the body rejecting the new stem cells.
Between Days -16 and -7, you will receive a low-level "test" dose of busulfan by vein over about 45 minutes to 1 hour. Test doses are used to study how your body breaks down busulfan and decide the dose of busulfan that you will receive. You may receive the test dose before Day -6 as an outpatient in the clinic, or on Day -6 as an inpatient in the hospital.
Blood (about 1 teaspoon each time) will then be drawn for PK testing up to 11 times over the 11 hours after the busulfan test dose and on Day -4. PK testing measures the amount of study drug in the body at different time points. The study staff will tell you more about the PK testing schedule.
A heparin lock line will be placed in your vein before the PK testing to lower the number of needle sticks needed for these draws. If for any reason it is not possible for the PK tests to be performed, you will receive the standard dose of busulfan.
On Day -7 or Day -6, you will be admitted to the hospital and given fluids through a CVC to hydrate you.
On Days -5, -4, -3, and -2, you will receive clofarabine through a CVC over 1 hour.
On Days -4, -3, and -2, you will receive busulfan through a CVC over 3 hours.
If you will receive stem cells from a donor whose cells do not match your own cells closely, on Days -3 and -2 you will also receive antithymocyte globulin (ATG) by vein over 4 hours. This will help to reduce the risk of your body rejecting the transplant. If your transplant will involve haploidentical stem cells, you will not receive ATG on Days -3 and -2.
On Day -1, you will receive TBI one time.
Stem Cell Transplant:
On Day 0, you will have an allogeneic or haploidentical stem cell transplant through the CVC. Allogeneic stem cells come from a donor whose cells closely match your own cells. Haploidentical stem cells come from a donor whose cells do not match your own cells as closely, but they are specially processed to help prevent graft versus host disease (GVHD).
Receiving stem cells is similar to receiving a blood transfusion. The time required to receive the stem cells will depend on the type of cells you are receiving. Receiving cord blood stem cells can take several minutes. Receiving bone marrow and blood stem cells may take several hours.
You will receive G-CSF (filgrastim) (which helps to produce white blood cells) as an injection under the skin once a day, starting 1 week after the transplant, until your blood cell levels return to normal.
You will receive drugs (mycophenolate mofetil (MMF), tacrolimus and/or methotrexate) to help prevent side effects, such as GVHD. You will receive methylprednisolone if you develop GVHD.
You will stay in the hospital for about 4 weeks after the stem cell transplantation.
If you had a haploidentical stem cell transplant, on Days 3 and 4 after your stem cell transplant, you will receive cyclophosphamide through a CVC over 3 hours. Mesna will be given by vein at the same time you are given each dose of cyclophosphamide, to help protect your bladder from bleeding.
Study Visits:
Beginning on Day -9, once a day while you are in the hospital:
- You will have a physical exam, including measurements of your vital signs.
- You will be asked if you have had any side effects.
- Blood (about 4 tablespoons) will be drawn to test your blood cell counts. Two (2) times a week, this blood will be also be used for routine tests.
After you are out of the hospital, 2 times a month until it has been 100 days after the transplant:
- You will have a physical exam, including measurements of your vital signs and weight.
- You will be asked if you have had any side effects.
- Blood (about 4 tablespoons) will be drawn for routine tests.
About 1, 3, 6, and 12 months after the transplant, blood (about 4 tablespoons) will be drawn to check the status of the disease. You will also have bone marrow aspirations to check the status of the disease. You will also have a physical exam.
If the doctor thinks it is necessary, you may have extra tests and procedures.
Length of Study:
You will be on study for about 1 year. You will be taken off study if the disease gets worse or needs further treatment.
Follow-Up:
If you live close to M. D. Anderson, you will return to the clinical once every several months for a physical exam. At these visits, blood (about 3 teaspoons) will be drawn for routine tests.
You and/or your local doctor will be called every several months and asked about your health status and if the leukemia or MDS has come back.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Thio-Clo-Bu with Allo SCT | Experimental | Drug: Thiotepa, Drug: Clofarabine, Drug: Busulfan, Procedure: Allogeneic Stem Cell Transplantation, Drug: Thymoglobulin (ATG), Drug: G-CSF (Filgrastim), Drug: Tacrolimus, Drug: Methotrexate, Drug: Cyclophosphamide, Drug: MesnaPre-transplant conditioning regimen: Thiotepa (Thio) + Clofarabine (Clo) + Busulfan (Blu) + Allogeneic Stem Cell Transplantation (Allo SCT) + ATG + G-CSF Post haploidentical stem cell transplant participants: Cyclophosphamide 50 mg/kg by vein on Days + 3 and + 4. Mesna 10 mg/kg by vein just prior to the first dose of cyclophosphamide, repeated every 4 hours for a total of ten (10) doses. |
Who may qualify
- Ages
- Up to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (18 listed)
- Diagnosed with one of the following diseases:
- Acute myelogenous leukemia (AML) in induction failure, relapse, past first remission, or CR1 considered at risk for relapse
- Myelodysplastic syndromes with International Prognostic Scoring System score (IPSS score) >/= 2 or myelodysplasia that has not responded to chemotherapy
- Biphenotypic leukemia
- Acute lymphocytic leukemia with induction failure, first complete remission with high risk cytogenetics (e.g. Philadelphia positive chromosome, t(4:11) Remission requiring more than 2 chemotherapy to achieve remission, or any stage beyond CR1
Key exclusion criteria (4 listed)
- Pregnancy in women of child bearing potential (pregnancy test performed within 2 weeks of study entry).
- HIV positive (highly immunosuppressive treatment)
- Active CNS leukemia
- Chronic or active Hepatitis B or Hepatitis C. If questions about liver health discuss with PI and strongly consider liver biopsy.
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 |
|---|---|---|
| ThiotepaAlso: Thio5 mg/kg through a central venous catheter (CVC) over 2 hours on Day -8. | Drug | Thio-Clo-Bu with Allo SCT |
| ClofarabineAlso: Clo, Clofarex, Clolar40 mg/m^2 through a central venous catheter (CVC) over 1 hour daily on 4 consecutive days (Days -6 through -3). | Drug | Thio-Clo-Bu with Allo SCT |
| BusulfanAlso: Busulfex, MyleranTest dose of 0.5 mg/kg through a central venous catheter (CVC)over 30 minutes on Day -7. High dose 5,000 µMol-min through a central venous catheter (CVC) over 3 hours on Days -5, -4, and -3. | Drug | Thio-Clo-Bu with Allo SCT |
| Allogeneic Stem Cell TransplantationAlso: ASCT, SCTInfusion of stem cells through through a central venous catheter (CVC) On Day 0. | Procedure or surgery | Thio-Clo-Bu with Allo SCT |
| Thymoglobulin (ATG)Also: Antithymocyte globulin1.25 mg/kg by vein on Day -4 and 1.75 mg/kg on Day -3. | Drug | Thio-Clo-Bu with Allo SCT |
| G-CSF (Filgrastim)Also: Neupogen5 µg/kg Injection under the skin once a day, starting 1 week after transplant, until blood cell levels return to normal. | Drug | Thio-Clo-Bu with Allo SCT |
| TacrolimusAlso: PrografStarting dose of 0.015 mg/kg (ideal body weight) as a 24 hour continuous infusion daily, to be changed to oral dosing when tolerated. Tacrolimus is to be tapered as indicated after transplant day 90, if no GVHD is present. Tacrolimus is adjusted trough level of 5-15 ng/mL. | Drug | Thio-Clo-Bu with Allo SCT |
| Methotrexate5 mg/m2 by vein on Days 1, 3 and 6 and Day +11 post transplant. The Day 11 methotrexate dose may be held as indicated if mucositis is present. | Drug | Thio-Clo-Bu with Allo SCT |
| CyclophosphamideAlso: Cytoxan, NeosarPost haploidentical stem cell transplant participants: 50 mg/kg by vein on Days + 3 and + 4. | Drug | Thio-Clo-Bu with Allo SCT |
| MesnaAlso: MesnexPost haploidentical stem cell transplant participants: 10 mg/kg by vein just prior to the first dose of cyclophosphamide, repeated every 4 hours for a total of ten (10) doses. | Drug | Thio-Clo-Bu with Allo SCT |
Primary outcome
Number of Participants With Survival Rate at 100 Days Post-transplant
Time frame: 100 days post-transplant
The toxicities will be monitored and scored on a daily basis following the methods of Simon R. Practical Bayesian Guideline for Phase IIB Clinical Trials. A Bayesian stopping rule will be used to stop the trial if there is a 90% chance that the true toxicity rate exceeds the target toxicity rate of 0.25.
6 secondary outcomes
Number of Participants With Disease Free Survival
Time frame: Up to 2 years post transplant
Overall Survival Rate
Time frame: Up to 3 years post transplant
Graft vs Host Disease (GVHD)
Time frame: Up to 30 days post transplant
Engraftment
Time frame: up to 100 days post transplant
Number of Participants With Serious Adverse Events
Time frame: up to 30 days post transplant
Relapse Rate of Participants Treated With Thiotepa, Busulfan, and Clofarabine
Time frame: Up to 2 years post transplant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2020.
- 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.
Kris M. Mahadeo, 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 Thiotepa, Clofarabine and Busulfan in people with Stem Cell Transplantation and Leukemia, 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 18 inclusion and 4 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 7 Apr 2020. 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 7 Apr 2020). 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?
Number of Participants With Survival Rate at 100 Days Post-transplant (time frame: 100 days post-transplant). 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 7 Apr 2020.