Thiotepa-Clofarabine-Busulfan With Allogeneic Stem Cell Transplant for High Risk Malignancies
2 other identifiers
interventional
60
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Mar 2009
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 2, 2009
CompletedFirst Submitted
Initial submission to the registry
March 5, 2009
CompletedFirst Posted
Study publicly available on registry
March 6, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 9, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
March 9, 2019
CompletedResults Posted
Study results publicly available
April 7, 2020
CompletedApril 7, 2020
March 1, 2020
10 years
March 5, 2009
March 13, 2020
March 25, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
100 days post-transplant
Secondary Outcomes (6)
Number of Participants With Disease Free Survival
Up to 2 years post transplant
Overall Survival Rate
Up to 3 years post transplant
Graft vs Host Disease (GVHD)
Up to 30 days post transplant
Engraftment
up to 100 days post transplant
Number of Participants With Serious Adverse Events
up to 30 days post transplant
- +1 more secondary outcomes
Study Arms (1)
Thio-Clo-Bu with Allo SCT
EXPERIMENTALPre-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.
Interventions
5 mg/kg through a central venous catheter (CVC) over 2 hours on Day -8.
40 mg/m\^2 through a central venous catheter (CVC) over 1 hour daily on 4 consecutive days (Days -6 through -3).
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.
Infusion of stem cells through through a central venous catheter (CVC) On Day 0.
1.25 mg/kg by vein on Day -4 and 1.75 mg/kg on Day -3.
5 µg/kg Injection under the skin once a day, starting 1 week after transplant, until blood cell levels return to normal.
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.
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.
Post haploidentical stem cell transplant participants: 50 mg/kg by vein on Days + 3 and + 4.
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.
Eligibility Criteria
You may qualify if:
- 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
- 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.
- +3 more criteria
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Kris M Mahadeo, Associate Professor, Pediatrics - Patient Care
- Organization
- UT MD Anderson Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Kris M. Mahadeo, MD
M.D. Anderson Cancer Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 5, 2009
First Posted
March 6, 2009
Study Start
March 2, 2009
Primary Completion
March 9, 2019
Study Completion
March 9, 2019
Last Updated
April 7, 2020
Results First Posted
April 7, 2020
Record last verified: 2020-03