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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by M.D. Anderson Cancer Center
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00857389
First received: March 5, 2009
Last updated: July 7, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Thiotepa-Clofarabine-Busulfan With Allogeneic Stem Cell Transplant for High Risk Malignancies

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Relapse-free Survival Rate [ Time Frame: 100 days post-transplant ] [ Designated as safety issue: No ]
    Number of participants out of total participants without detection of histologic diagnosis of recurrent disease on day 100 following stem cell transplant.


Estimated Enrollment: 60
Study Start Date: March 2009
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Mesnex

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00857389

Contacts
Contact: Laura L. Worth, MD, PhD 713-792-6620

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Laura L. Worth, MD, PhD         
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Laura L. Worth, MD, PhD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00857389     History of Changes
Other Study ID Numbers: 2008-0363, NCI-2012-01630
Study First Received: March 5, 2009
Last Updated: July 7, 2014
Health Authority: United States: Institutional Review Board

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

Additional relevant MeSH terms:
Leukemia
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Mesna
Antilymphocyte Serum
Busulfan
Cyclophosphamide
Methotrexate
Thiotepa
Lenograstim
Tacrolimus
Clofarabine
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Immunologic Factors
Immunosuppressive Agents
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antirheumatic Agents
Abortifacient Agents, Nonsteroidal

ClinicalTrials.gov processed this record on August 01, 2014