Vorinostat With Gemcitabine, Busulfan, and Melphalan With Stem Cell Transplant (SCT) in Relapsed or Refractory Lymphoid Malignancies
The goal of this clinical research study is to find the highest tolerable dose of vorinostat that can be given with gemcitabine, busulfan, and melphalan with a stem cell transplant. Researchers also want to learn about the safety and level of effectiveness of this combination.
Busulfan and melphalan are designed to kill cancer cells by binding to DNA (the genetic material of cells), which may cause cancer cells to die.
Gemcitabine is designed to disrupt the growth of cancer cells, which may cause cancer cells to die. It may help to increase the effect of busulfan and melphalan on cancer cells by not allowing these cells to repair the DNA damage caused by busulfan or melphalan.
Vorinostat is designed to open up the DNA and allow greater access to drugs that bind to DNA, such as gemcitabine, busulfan and melphalan.
Procedure: Stem Cell Infusion
Drug: Dexamethasone acetate
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Vorinostat (SAHA) Combined With High-Dose Gemcitabine, Busulfan, and Melphalan With Autologous Hematopoietic Cell Support for Patients With Relapsed or Refractory Lymphoid Malignancies|
- Dose Limiting Toxicity (DLT) [ Time Frame: About 100 days after the transplant ] [ Designated as safety issue: Yes ]Bone marrow aspiration and biopsy, CT scan of the neck, chest, abdomen, and pelvis to check the status of the disease. Dose limiting toxicity (DLT) is defined as any grade 4 non-hematological, non-infectious toxicity attributable to the preparative regimen, or any grade 3 mucositis or skin toxicity that lasts more than 3 days at peak severity, or any grade 4 mucositis or skin toxicity of any duration. Unadjusted relapse-free survival (RFS) and overall survival (OS) will be estimated by the method of Kaplan and Meier.
|Study Start Date:||August 2011|
|Estimated Primary Completion Date:||August 2016 (Final data collection date for primary outcome measure)|
Experimental: Vorinostat + GemBuMel
Vorinostat 200 mg by mouth on Days -8 to -2. Gemcitabine loading dose of 75 mg/m2 followed by continuous infusion. Remaining dose is 10 mg/m2/min on Day -8 and -3. Busulfan pharmacokinetics (PK) will be performed with the first dose of 105 mg/m2 by vein on Day -8. The doses of days -6 and -5 will be subsequently adjusted to target an AUC of 4,000 microMol.min-1. In the event that PK adjusting were not possible, a dose of busulfan of 105 mg/m2 will be administered on days -6 and -5. Melphalan 60 mg/m2 by vein on Days -2 and -3. Stem cells by vein over about 30-60 minutes on Day 0. Rituximab 375 mg/m2 on days +1 and +8 for CD20+ tumors. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +5 and continuing until neutrophil recovery is documented. Palifermin 60 mcg/kg by vein daily for 6 doses starting on Day 0. Dexamethasone 8 mg by vein twice a day from day -8 AM to day -2 PM.
Starting dose: 200 mg by mouth on Days -8 to -2.
Other Names:Drug: Gemcitabine
Starting dose: 2175 mg/m2 by vein on Days -8 and -3. This includes the gemcitabine 75 mg/m2 loading dose.
Other Names:Drug: Busulfan
AUC: 4,000 microM.min/day, or 105 mg/m2/day) on Days -8 to -5.
Pharmacokinetics will be performed with the first dose of 32 mg/m2 by vein on Day -8. The doses on Days -6 and -5 will be subsequently adjusted to target an AUC of 4,000 microMol.min-1. In the event that PK adjusting not possible, a dose of busulfan of 105 mg/m2 will be administered on days -6 and -5.
Other Names:Drug: Melphalan
60 mg/m2 by vein on Days -3 and -2.
Other Name: AlkeranProcedure: Stem Cell Infusion
Infusion of stem cells by vein on Day 0.Drug: Rituximab
375 mg/m2 on days +1 and +8 for patients with CD20+ tumors.
Other Name: RituxanDrug: G-CSF
5 mcg/kg/day (rounded up the nearest vial) subcutaneously beginning on Day +5 and continuing until neutrophil recovery is documented.
Other Names:Drug: Palifermin
60 mcg/kg by vein daily for 6 doses. Three doses administrated prior to start chemo (24 hours must elapse between the last dose and first therapeutic dose of chemo) and three doses after the last chemo starting on day 0.
Other Name: KepivanceDrug: Dexamethasone acetate
8 mg by vein twice a day from day -8 AM to day -2 PM.
Other Name: Decadron
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01421173
|United States, Texas|
|University of Texas MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Yago Nieto, MD,PHD||M.D. Anderson Cancer Center|