Thiotepa-Clofarabine-Busulfan With Allogeneic Stem Cell Transplant for High Risk Malignancies

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00857389
• Collaborator: (none)
• Enrollment: 60
• Location: 1
• Arm: 1
• Actual Duration (Months): 120.2
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief 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 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.

Condition or Disease	Intervention/Treatment	Phase
Stem Cell Transplantation; Leukemia; Lymphoma	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	Phase 2

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

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Thiotepa-Clofarabine-Busulfan With Allogeneic Stem Cell Transplant for High Risk Malignancies
• Actual Study Start Date: Mar 2, 2009
• Actual Primary Completion Date: Mar 9, 2019
• Actual Study Completion Date: Mar 9, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Thio-Clo-Bu with Allo SCT 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.

Drug: Thiotepa; 5 mg/kg through a central venous catheter (CVC) over 2 hours on Day -8.; Other Names: Thio ; Drug: Clofarabine; 40 mg/m^2 through a central venous catheter (CVC) over 1 hour daily on 4 consecutive days (Days -6 through -3).; Other Names: Clo Clofarex Clolar ; Drug: Busulfan; 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.; Other Names: Busulfex Myleran ; Procedure: Allogeneic Stem Cell Transplantation; Infusion of stem cells through through a central venous catheter (CVC) On Day 0.; Other Names: ASCT SCT ; Drug: Thymoglobulin (ATG); 1.25 mg/kg by vein on Day -4 and 1.75 mg/kg on Day -3.; Other Names: Antithymocyte globulin ; Drug: G-CSF (Filgrastim); 5 µg/kg Injection under the skin once a day, starting 1 week after transplant, until blood cell levels return to normal.; Other Names: Neupogen ; Drug: Tacrolimus; 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.; Other Names: Prograf ; Drug: Methotrexate; 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.; Drug: Cyclophosphamide; Post haploidentical stem cell transplant participants: 50 mg/kg by vein on Days + 3 and + 4.; Other Names: Cytoxan Neosar ; Drug: Mesna; 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.; Other Names: Mesnex

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Survival Rate at 100 Days Post-transplant [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.

Secondary Outcome Measures

1. Number of Participants With Disease Free Survival [Up to 2 years post transplant]

   Kaplan-Meier product limit method to estimate the disease free survival.

2. Overall Survival Rate [Up to 3 years post transplant]

   Overall Survival Rate will be estimated using the Kaplan-Meier method.

3. Graft vs Host Disease (GVHD) [Up to 30 days post transplant]

   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.

4. Engraftment [up to 100 days post transplant]

   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 .

5. Number of Participants With Serious Adverse Events [up to 30 days post transplant]

   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.

6. Relapse Rate of Participants Treated With Thiotepa, Busulfan, and Clofarabine [Up to 2 years post transplant]

   Relapse Rate will be estimated using the Kaplan-Meier method.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Diagnosed with one of the following diseases:

2. Acute myelogenous leukemia (AML) in induction failure, relapse, past first remission, or CR1 considered at risk for relapse

3. Myelodysplastic syndromes with International Prognostic Scoring System score (IPSS score) >/= 2 or myelodysplasia that has not responded to chemotherapy

4. Biphenotypic leukemia

5. 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

6. 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

7. Non-Hodgkin's Lymphoma - induction failures, second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant)

8. Hodgkin's disease - induction failure, second or later complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant).

9. Chronic Lymphocytic Leukemia that has failed induction therapy or Rai Stages 2-4

10. 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.

11. Age </= 60 years.

12. Lansky performance score >/= 50% for patients </= 16 years of age, or Zubrod performance status score of 0-2 for patients > 16 years of age.

13. Cardiac function - left ventricular ejection fraction >/= 40%.

14. 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.

15. Serum creatinine < 1.6 mg/dL or creatinine clearance >/= 50 ml/min.

16. SGPT </= 200 IU/mL, serum bilirubin < 1.5 x normal.

17. Written informed consent and assent as is age appropriate.

18. No active infection.

Exclusion Criteria:

1. Pregnancy in women of child bearing potential (pregnancy test performed within 2 weeks of study entry).

2. HIV positive (highly immunosuppressive treatment)

3. Active CNS leukemia

4. Chronic or active Hepatitis B or Hepatitis C. If questions about liver health discuss with PI and strongly consider liver biopsy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center

Investigators

• Principal Investigator: Kris M. Mahadeo, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 11, 2013

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00857389
• Other Study ID Numbers: 2008-0363; NCI-2012-01630
• First Posted: Mar 6, 2009
• Last Update Posted: Apr 7, 2020
• Last Verified: Mar 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by M.D. Anderson Cancer Center: 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; G-CSF; Filgrastim; Neupogen; Cyclophosphamide; Cytoxan; Neosar; Mesna; Mesnex; Tacrolimus; Prograf; Methotrexate
• Additional relevant MeSH terms: Leukemia; Cyclophosphamide; Busulfan; Thiotepa; Methotrexate; Clofarabine; Tacrolimus; Thymoglobulin; Antilymphocyte Serum

Study Results

Participant Flow

Recruitment Details	This study received IRB approval October 1, 2008 and was opened to recruitment March 2, 2009. The study remained open to recruitment until August 4, 2015. The study was terminated by the local IRB on April 09, 2019.
Pre-assignment Detail	Of the 60 participants enrolled, 2 participants did not proceed to transplant no data were collected for those two participants

Arm/Group Title	Conditioning Reg- Thiotepa, Busulfan, and Clofarabine
Arm/Group Description	Single arm study
Period Title: Overall Study
STARTED	60
COMPLETED	58
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Conditioning Reg- Thiotepa, Busulfan, and Clofarabine
Arm/Group Description	The 5 mg/kg over 1 hr. Busulfan was administered x 3 days over 3 hr to a daily AUC of 5,000 mcMol-min +/-10%. Clofarabine 40mg/m2 was infused over 1 hr daily x 4 days
Overall Participants	58
Age (Count of Participants)
<=18 years	24 41.4%
Between 18 and 65 years	34 58.6%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	28 48.3%
Male	30 51.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	18 31%
Not Hispanic or Latino	0 0%
Unknown or Not Reported	40 69%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	4 6.9%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	8 13.8%
White	25 43.1%
More than one race	0 0%
Unknown or Not Reported	21 36.2%
Region of Enrollment (participants) [Number]
United States	58 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Survival Rate at 100 Days Post-transplant
Description	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.
Time Frame	100 days post-transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Conditioning Reg- Thiotepa, Busulfan, and Clofarabine
Arm/Group Description	The 5 mg/kg over 1 hr. Busulfan was administered x 3 days over 3 hr to a daily AUC of 5,000 mcMol-min +/-10%. Clofarabine 40mg/m2 was infused over 1 hr daily x 4 days
Measure Participants	58
Count of Participants [Participants]	45 77.6%

2. Secondary Outcome

Title	Number of Participants With Disease Free Survival
Description	Kaplan-Meier product limit method to estimate the disease free survival.
Time Frame	Up to 2 years post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Conditioning Reg- Thiotepa, Busulfan, and Clofarabine
Arm/Group Description	The 5 mg/kg over 1 hr. Busulfan was administered x 3 days over 3 hr to a daily AUC of 5,000 mcMol-min +/-10%. Clofarabine 40mg/m2 was infused over 1 hr daily x 4 days
Measure Participants	58
Count of Participants [Participants]	32 55.2%

3. Secondary Outcome

Title	Overall Survival Rate
Description	Overall Survival Rate will be estimated using the Kaplan-Meier method.
Time Frame	Up to 3 years post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Conditioning Reg- Thiotepa, Busulfan, and Clofarabine
Arm/Group Description	The 5 mg/kg over 1 hr. Busulfan was administered x 3 days over 3 hr to a daily AUC of 5,000 mcMol-min +/-10%. Clofarabine 40mg/m2 was infused over 1 hr daily x 4 days
Measure Participants	58
Median (Full Range) [days]	320

4. Secondary Outcome

Title	Graft vs Host Disease (GVHD)
Description	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.
Time Frame	Up to 30 days post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Conditioning Reg- Thiotepa, Busulfan, and Clofarabine
Arm/Group Description	The 5 mg/kg over 1 hr. Busulfan was administered x 3 days over 3 hr to a daily AUC of 5,000 mcMol-min +/-10%. Clofarabine 40mg/m2 was infused over 1 hr daily x 4 days
Measure Participants	58
Count of Participants [Participants]	34 58.6%

5. Secondary Outcome

Title	Engraftment
Description	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 .
Time Frame	up to 100 days post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Conditioning Reg- Thiotepa, Busulfan, and Clofarabine
Arm/Group Description	The 5 mg/kg over 1 hr. Busulfan was administered x 3 days over 3 hr to a daily AUC of 5,000 mcMol-min +/-10%. Clofarabine 40mg/m2 was infused over 1 hr daily x 4 days
Measure Participants	58
Count of Participants [Participants]	52 89.7%

6. Secondary Outcome

Title	Number of Participants With Serious Adverse Events
Description	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.
Time Frame	up to 30 days post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Conditioning Reg- Thiotepa, Busulfan, and Clofarabine
Arm/Group Description	The 5 mg/kg over 1 hr. Busulfan was administered x 3 days over 3 hr to a daily AUC of 5,000 mcMol-min +/-10%. Clofarabine 40mg/m2 was infused over 1 hr daily x 4 days
Measure Participants	58
Count of Participants [Participants]	52 89.7%

7. Secondary Outcome

Title	Relapse Rate of Participants Treated With Thiotepa, Busulfan, and Clofarabine
Description	Relapse Rate will be estimated using the Kaplan-Meier method.
Time Frame	Up to 2 years post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Conditioning Reg- Thiotepa, Busulfan, and Clofarabine
Arm/Group Description	The 5 mg/kg over 1 hr. Busulfan was administered x 3 days over 3 hr to a daily AUC of 5,000 mcMol-min +/-10%. Clofarabine 40mg/m2 was infused over 1 hr daily x 4 days
Measure Participants	58
Count of Participants [Participants]	26 44.8%

Adverse Events

Time Frame	Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Arm/Group Title	Conditioning Reg- Thiotepa, Busulfan, and Clofarabine
Arm/Group Description	The 5 mg/kg over 1 hr. Busulfan was administered x 3 days over 3 hr to a daily AUC of 5,000 mcMol-min +/-10%. Clofarabine 40mg/m2 was infused over 1 hr daily x 4 days
All Cause Mortality
	Conditioning Reg- Thiotepa, Busulfan, and Clofarabine
	Affected / at Risk (%)	# Events
Total	16/58 (27.6%)
Serious Adverse Events
	Conditioning Reg- Thiotepa, Busulfan, and Clofarabine
	Affected / at Risk (%)	# Events
Total	52/58 (89.7%)
Blood and lymphatic system disorders
Febrile Neutropenia	30/58 (51.7%)
Low granulocyte	3/58 (5.2%)
Cardiac disorders
Ejection fraction decreased	1/58 (1.7%)
Hepatobiliary disorders
VOD	8/58 (13.8%)
Immune system disorders
Allergic reaction	2/58 (3.4%)
Investigations
ALK increase	2/58 (3.4%)
ALT increase	12/58 (20.7%)
Creatinine Increased	5/58 (8.6%)
T bilirubin increased	6/58 (10.3%)
Nervous system disorders
Hydrocephalus	1/58 (1.7%)
Headache	1/58 (1.7%)
Encephalopathy	1/58 (1.7%)
Renal and urinary disorders
Hemorrhagic Cystitis	10/58 (17.2%)
Respiratory, thoracic and mediastinal disorders
ARDS- Acute respiratory Distress Syndrome	1/58 (1.7%)
DAH-diffuse alveolar hemorrhage	3/58 (5.2%)
Pneumonitis	4/58 (6.9%)
Pulmonary edema	1/58 (1.7%)
Skin and subcutaneous tissue disorders
Rash	15/58 (25.9%)
Other (Not Including Serious) Adverse Events
	Conditioning Reg- Thiotepa, Busulfan, and Clofarabine
	Affected / at Risk (%)	# Events
Total	57/58 (98.3%)
Blood and lymphatic system disorders
Bleeding	1/58 (1.7%)
HSCT related microangiopathy (TA-TMA)	2/58 (3.4%)
Secondary graft failure	3/58 (5.2%)
Cardiac disorders
Cardiomyopathy	1/58 (1.7%)
Ejection fraction decreased	2/58 (3.4%)
Dysrhythmia	1/58 (1.7%)
Pericarditis	1/58 (1.7%)
Eye disorders
Blurred Vision	2/58 (3.4%)
Dry eye	5/58 (8.6%)
Gastrointestinal disorders
Abodominal Pain	3/58 (5.2%)
Diarrhea	44/58 (75.9%)
Gastrointestinal bleeding	4/58 (6.9%)
Hematochezia	1/58 (1.7%)
Lower GI track obstruction	2/58 (3.4%)
Oral mucositis	49/58 (84.5%)
Nausea	57/58 (98.3%)
General disorders
Fever	22/58 (37.9%)
Fluid overload	22/58 (37.9%)
Infections and infestations
Infection	53/58 (91.4%)
Investigations
ALK increased	10/58 (17.2%)
ALT increase	18/58 (31%)
Creatinine Increased	9/58 (15.5%)
Low platelet	2/58 (3.4%)
T bilirubin increased	14/58 (24.1%)
Metabolism and nutrition disorders
Hyperglycemia	1/58 (1.7%)
Musculoskeletal and connective tissue disorders
Bone Pain	5/58 (8.6%)
Flu like symdrome	1/58 (1.7%)
Generalized muscle weakness	1/58 (1.7%)
Nervous system disorders
AMS- altered mental status	2/58 (3.4%)
Confusion	1/58 (1.7%)
Diplopia	1/58 (1.7%)
Dizziness	2/58 (3.4%)
Headache	10/58 (17.2%)
Neuropathy	3/58 (5.2%)
Seizure	3/58 (5.2%)
Psychiatric disorders
Hallucination	1/58 (1.7%)
Renal and urinary disorders
Cystitis noninfective	1/58 (1.7%)
Hemorrhagic Cystitis	14/58 (24.1%)
Respiratory, thoracic and mediastinal disorders
Broncholitis Obliterans	2/58 (3.4%)
DAH-diffuse alveolar hemorrhage	1/58 (1.7%)
Pneumonitis	8/58 (13.8%)
Skin and subcutaneous tissue disorders
Cellulitis	1/58 (1.7%)
Hand Foot syndrom	3/58 (5.2%)
Pruritis	4/58 (6.9%)
Rash	23/58 (39.7%)
SK OTH	1/58 (1.7%)
Vascular disorders
Hypertension	8/58 (13.8%)
Hypotension	2/58 (3.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.