Allogeneic Stem Cell Transplant for Chronic Lymphocytic Leukemia (CLL)
The goal of this clinical research study is to learn the highest tolerable dose of gemcitabine (out of 4 possible doses) that can be given in combination with busulfan and clofarabine before an allogeneic stem cell transplant. Researchers also want to learn if this combination can help to control CLL. The safety of this treatment will also be studied.
Busulfan is designed to bind to DNA (the genetic material of cells), which may cause cancer cells to die. It is commonly used in stem cell transplants.
Clofarabine and gemcitabine are designed to block the growth of cancer cells, which may cause the cancer cells to die.
Procedure: Allogeneic Stem Cell Transplantation
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Clofarabine, Gemcitabine and Busulfan Followed by Allogeneic Stem Cell Transplantation for Chronic Lymphocytic Leukemia (CLL)|
- Maximum Tolerated Dose (MTD) of Gemcitabine with Busulfan and Clofarabine [ Time Frame: 30 days after allogeneic stem cell transplant ] [ Designated as safety issue: Yes ]Toxicity defined as any of the three events grade 4 mucositis, grade 4 skin toxicity, or death from any cause, occurring within 30 days from transplant.
- Success Rate [ Time Frame: 100 days ] [ Designated as safety issue: No ]Success rate defined as all of three efficacy outcomes that patient is (i) alive, (ii) engrafted, and (ii) without grade 3 or 4 (i.e., severe) graft versus host disease (GVHD) at 100 days post allogeneic transplant. Overall survival (OS), progression free survival (PFS), and time-to-engraftment all are defined from day of allogeneic transplant, to day of event.
|Study Start Date:||November 2012|
|Estimated Primary Completion Date:||November 2017 (Final data collection date for primary outcome measure)|
Experimental: Busulfan + Clofarabine + Gemcitabine + Transplant
Clofarabine administered at dose of 30 mg/m2 by vein infused over 1 hour on Days -6 through -3. Busulfan test dose of 32 mg/m2 based on actual body weight given by vein over 60 minutes. Busulfan administered at dose calculated to achieve a systemic exposure dose of 4000 µMol-min in normal saline over 3 hours by vein every 24 hours on Days -6 to -3, starting immediately after the completion of Clofarabine. Gemcitabine dosing begin at 275 mg/m2/dose by vein preceded by a loading dose of 75 mg/m2 administered as a bolus: 75 mg/m2 + (10mg/m2/ min × 10 min) = 175 mg/m2 .
Patients receiving a graft from a matched unrelated donor receive Thymoglobulin; 0.5 mg/kg on Day -3, 1.5 mg/kg on Day -2 and 2.0 mg/kg on Day -1.
Allogeneic hematopoietic cell transplantation on Day 0.
32 mg/m2 test dose by vein based on actual body weight given between Day -15 and Day -8.
Busulfan administered at dose calculated to achieve a systemic exposure dose of 4000 µMol-min in normal saline over 3 hours by vein every 24 hours on Days -6 to -3, starting one hour after the completion of Clofarabine.
Other Names:Drug: Clofarabine
30 mg/m2 diluted in NS to produce a final concentration of 0.4mg/mL by vein on Days -6 through -3.
Other Names:Drug: Gemcitabine
Phase I Starting Dose: 275 mg/m2 by vein preceded by a loading dose of 75 mg/m2 administered as a bolus on Days -6 and -4.
Phase II Starting Dose: Maximum tolerated dose (MTD) from Phase I.
Other Names:Drug: Thymoglobulin
0.5 mg/kg by vein on Day -3, 1.5 mg/kg on Day -2 and 2.0 mg/kg on Day -1 for patients receiving a graft from a matched unrelated donor.
Other Names:Procedure: Allogeneic Stem Cell Transplantation
Fresh or cryopreserved bone marrow or peripheral blood progenitor cells infused on Day 0.Drug: Filgrastim
5 mcg/kg subcutaneously 1 time each day starting 1 week after the transplant until blood cell levels return to normal.
Other Names:Drug: Tacrolimus
Starting dose of 0.015 mg/kg by vein as a 24 hour continuous infusion daily beginning on Day -2, adjusted to achieve a therapeutic level of 5-15 ng/ml. Tacrolimus is changed to oral dosing when tolerated and can be tapered off after day +90 if no GVHD is present.
Other Name: PrografDrug: Methotrexate
5 mg/m2 by vein on Days +1, +3, +6 and +11 post transplant.
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01629511
|Contact: Chitra M. Hosing, MD||713-792-8750|
|United States, Texas|
|University of Texas MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Chitra M. Hosing, MD||M.D. Anderson Cancer Center|