Vorinostat With Gemcitabine, Busulfan, and Melphalan With Stem Cell Transplant (SCT) in Relapsed or Refractory Lymphoid Malignancies
|ClinicalTrials.gov Identifier: NCT01421173|
Recruitment Status : Completed
First Posted : August 22, 2011
Last Update Posted : November 18, 2015
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.
|Condition or disease||Intervention/treatment||Phase|
|Lymphoma||Drug: Vorinostat Drug: Gemcitabine Drug: Busulfan Drug: Melphalan Procedure: Stem Cell Infusion Drug: Rituximab Drug: G-CSF Drug: Palifermin Drug: Dexamethasone acetate||Phase 1|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||78 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||August 2011|
|Actual Primary Completion Date :||September 2015|
|Actual Study Completion Date :||September 2015|
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 area under curve (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 cluster of differentiation antigen 20 (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.
Starting dose: 2175 mg/m2 by vein on Days -8 and -3. This includes the gemcitabine 75 mg/m2 loading dose.
AUC: 4,000 micrometer (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.
60 mg/m2 by vein on Days -3 and -2.
Other Name: Alkeran
Procedure: Stem Cell Infusion
Infusion of stem cells by vein on Day 0.
375 mg/m2 on days +1 and +8 for patients with CD20+ tumors.
Other Name: Rituxan
5 mcg/kg/day (rounded up the nearest vial) subcutaneously beginning on Day +5 and continuing until neutrophil recovery is documented.
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: Kepivance
Drug: Dexamethasone acetate
8 mg by vein twice a day from day -8 AM to day -2 PM.
Other Name: Decadron
- Recommended Dose of Vorinostat for combination with Gemcitabine/Busulfan/Melphalan (GemBuMel) based on Dose Limiting Toxicity (DLT) [ Time Frame: About 100 days after the transplant ]
No more than 2 patients enrolled at one time in new dose level, until toxicities of at least 1 of those are assessed & determined not to be DLT, no more patients enrolled at new dose level. Dose escalation of vorinostat starts at level 1a (200 mg/day) and Gemcitabine (2175 mg/m2/day). If level tolerable, dose proceeds from level 2a (300 mg) to level 11a (1000 mg) at increase of 100 mg per level. If level 1a were not tolerable, i.e., greater than 20% DLTs (determined by Continual Reassessment Method (CRM)), a decreased dose of gemcitabine (level 1b 1875 mg/m2) assigned and vorninostat escalation would be up to level 5b (600 mg) at increase of 100 mg per level instead.
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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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|