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

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ClinicalTrials.gov Identifier: NCT00857389
Recruitment Status : Active, not recruiting
First Posted : March 6, 2009
Last Update Posted : April 18, 2018
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
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 : March 2009
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine


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 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




Primary Outcome Measures :
  1. Relapse-free Survival Rate [ Time Frame: 100 days post-transplant ]
    Number of participants out of total participants without detection of histologic diagnosis of recurrent disease on day 100 following stem cell transplant.



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Ages Eligible for Study:   up to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00857389


Locations
United States, Texas
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

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00857389     History of Changes
Other Study ID Numbers: 2008-0363
NCI-2012-01630 ( Registry Identifier: NCI CTRP )
First Posted: March 6, 2009    Key Record Dates
Last Update Posted: April 18, 2018
Last Verified: April 2018

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

Additional relevant MeSH terms:
Cyclophosphamide
Methotrexate
Tacrolimus
Busulfan
Thymoglobulin
Thiotepa
Antilymphocyte Serum
Clofarabine
Lenograstim
Mesna
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Antimetabolites
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Calcineurin Inhibitors
Adjuvants, Immunologic