Trial Outcomes & Findings for Thiotepa-Clofarabine-Busulfan With Allogeneic Stem Cell Transplant for High Risk Malignancies (NCT NCT00857389)

Last Updated: 2020-04-07

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

60 participants

Primary outcome timeframe

100 days post-transplant

Results posted on

2020-04-07

Participant Flow

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.

Of the 60 participants enrolled, 2 participants did not proceed to transplant no data were collected for those two participants

Participant milestones

Participant milestones
Measure	Conditioning Reg- Thiotepa, Busulfan, and Clofarabine Single arm study
Overall Study STARTED	60
Overall Study COMPLETED	58
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Conditioning Reg- Thiotepa, Busulfan, and Clofarabine Single arm study
Overall Study Did not proceed to transplant	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Conditioning Reg- Thiotepa, Busulfan, and Clofarabine n=58 Participants 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
Age, Categorical <=18 years	24 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	34 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	28 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	40 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants
Race (NIH/OMB) White	25 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	21 Participants n=5 Participants
Region of Enrollment United States	58 participants n=5 Participants

PRIMARY outcome

Timeframe: 100 days post-transplant

Outcome measures

Outcome measures
Measure	Conditioning Reg- Thiotepa, Busulfan, and Clofarabine n=58 Participants 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
Number of Participants With Survival Rate at 100 Days Post-transplant	45 Participants

SECONDARY outcome

Timeframe: Up to 2 years post transplant

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

Outcome measures

Outcome measures
Measure	Conditioning Reg- Thiotepa, Busulfan, and Clofarabine n=58 Participants 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
Number of Participants With Disease Free Survival	32 Participants

SECONDARY outcome

Timeframe: Up to 3 years post transplant

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

Outcome measures

Outcome measures
Measure	Conditioning Reg- Thiotepa, Busulfan, and Clofarabine n=58 Participants 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 Survival Rate	320 days Interval 120.0 to 833.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Conditioning Reg- Thiotepa, Busulfan, and Clofarabine n=58 Participants 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
Graft vs Host Disease (GVHD)	34 Participants

SECONDARY outcome

Timeframe: 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 .

Outcome measures

Outcome measures
Measure	Conditioning Reg- Thiotepa, Busulfan, and Clofarabine n=58 Participants 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
Engraftment	52 Participants

SECONDARY outcome

Timeframe: up to 30 days post transplant

Outcome measures

Outcome measures
Measure	Conditioning Reg- Thiotepa, Busulfan, and Clofarabine n=58 Participants 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
Number of Participants With Serious Adverse Events	52 Participants

SECONDARY outcome

Timeframe: Up to 2 years post transplant

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

Outcome measures

Outcome measures
Measure	Conditioning Reg- Thiotepa, Busulfan, and Clofarabine n=58 Participants 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
Relapse Rate of Participants Treated With Thiotepa, Busulfan, and Clofarabine	26 Participants

Adverse Events

Conditioning Reg- Thiotepa, Busulfan, and Clofarabine

Serious events: 52 serious events

Other events: 57 other events

Deaths: 16 deaths

Serious adverse events

Serious adverse events
Measure	Conditioning Reg- Thiotepa, Busulfan, and Clofarabine n=58 participants at risk 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
Respiratory, thoracic and mediastinal disorders ARDS- Acute respiratory Distress Syndrome	1.7% 1/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Blood and lymphatic system disorders Febrile Neutropenia	51.7% 30/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Cardiac disorders Ejection fraction decreased	1.7% 1/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Respiratory, thoracic and mediastinal disorders DAH-diffuse alveolar hemorrhage	5.2% 3/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Investigations ALK increase	3.4% 2/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Immune system disorders Allergic reaction	3.4% 2/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Investigations ALT increase	20.7% 12/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Nervous system disorders Hydrocephalus	1.7% 1/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Investigations Creatinine Increased	8.6% 5/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Nervous system disorders Headache	1.7% 1/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Renal and urinary disorders Hemorrhagic Cystitis	17.2% 10/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Blood and lymphatic system disorders Low granulocyte	5.2% 3/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Respiratory, thoracic and mediastinal disorders Pneumonitis	6.9% 4/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Respiratory, thoracic and mediastinal disorders Pulmonary edema	1.7% 1/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Investigations T bilirubin increased	10.3% 6/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Hepatobiliary disorders VOD	13.8% 8/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Skin and subcutaneous tissue disorders Rash	25.9% 15/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Nervous system disorders Encephalopathy	1.7% 1/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.

Other adverse events

Other adverse events
Measure	Conditioning Reg- Thiotepa, Busulfan, and Clofarabine n=58 participants at risk 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
Gastrointestinal disorders Abodominal Pain	5.2% 3/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Investigations ALK increased	17.2% 10/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Investigations ALT increase	31.0% 18/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Nervous system disorders AMS- altered mental status	3.4% 2/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Blood and lymphatic system disorders Bleeding	1.7% 1/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Eye disorders Blurred Vision	3.4% 2/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Musculoskeletal and connective tissue disorders Bone Pain	8.6% 5/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Respiratory, thoracic and mediastinal disorders Broncholitis Obliterans	3.4% 2/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Cardiac disorders Cardiomyopathy	1.7% 1/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Skin and subcutaneous tissue disorders Cellulitis	1.7% 1/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Nervous system disorders Confusion	1.7% 1/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Investigations Creatinine Increased	15.5% 9/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Renal and urinary disorders Cystitis noninfective	1.7% 1/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Respiratory, thoracic and mediastinal disorders DAH-diffuse alveolar hemorrhage	1.7% 1/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Gastrointestinal disorders Diarrhea	75.9% 44/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Nervous system disorders Diplopia	1.7% 1/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Nervous system disorders Dizziness	3.4% 2/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Eye disorders Dry eye	8.6% 5/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Cardiac disorders Ejection fraction decreased	3.4% 2/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Cardiac disorders Dysrhythmia	1.7% 1/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
General disorders Fever	37.9% 22/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Musculoskeletal and connective tissue disorders Flu like symdrome	1.7% 1/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
General disorders Fluid overload	37.9% 22/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Gastrointestinal disorders Gastrointestinal bleeding	6.9% 4/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	1.7% 1/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Psychiatric disorders Hallucination	1.7% 1/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Skin and subcutaneous tissue disorders Hand Foot syndrom	5.2% 3/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Nervous system disorders Headache	17.2% 10/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Gastrointestinal disorders Hematochezia	1.7% 1/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Renal and urinary disorders Hemorrhagic Cystitis	24.1% 14/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Blood and lymphatic system disorders HSCT related microangiopathy (TA-TMA)	3.4% 2/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Metabolism and nutrition disorders Hyperglycemia	1.7% 1/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Vascular disorders Hypertension	13.8% 8/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Vascular disorders Hypotension	3.4% 2/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Infections and infestations Infection	91.4% 53/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Investigations Low platelet	3.4% 2/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Gastrointestinal disorders Lower GI track obstruction	3.4% 2/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Nervous system disorders Neuropathy	5.2% 3/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Gastrointestinal disorders Oral mucositis	84.5% 49/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Cardiac disorders Pericarditis	1.7% 1/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Respiratory, thoracic and mediastinal disorders Pneumonitis	13.8% 8/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Skin and subcutaneous tissue disorders Pruritis	6.9% 4/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Skin and subcutaneous tissue disorders Rash	39.7% 23/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Blood and lymphatic system disorders Secondary graft failure	5.2% 3/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Nervous system disorders Seizure	5.2% 3/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Skin and subcutaneous tissue disorders SK OTH	1.7% 1/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Investigations T bilirubin increased	24.1% 14/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.
Gastrointestinal disorders Nausea	98.3% 57/58 • Adverse events that were related to the preparative regimen and stem cell infusion unil 30 days post transplant.

Additional Information

Kris M Mahadeo, Associate Professor, Pediatrics - Patient Care

UT MD Anderson Cancer Center

Phone: (713) 792-2873

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place