Vorinostat With Gemcitabine, Busulfan, and Melphalan With Stem Cell Transplant (SCT) in Relapsed or Refractory Lymphoid Malignancies
This study is currently recruiting participants.
Verified May 2013 by M.D. Anderson Cancer Center
Sponsor:
M.D. Anderson Cancer Center
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01421173
First received: August 18, 2011
Last updated: May 2, 2013
Last verified: May 2013
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
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 | Intervention | Phase |
|---|---|---|
|
Lymphoma |
Drug: Vorinostat Drug: Gemcitabine Drug: Busulfan Drug: Melphalan Procedure: Stem Cell Infusion Drug: Rituximab Drug: G-CSF Drug: Palifermin |
Phase 1 |
| Study Type: | Interventional |
| 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 |
Resource links provided by NLM:
Drug Information available for:
Busulfan
Melphalan
Melphalan hydrochloride
Gemcitabine
Filgrastim
Gemcitabine hydrochloride
Lenograstim
Granulocyte colony-stimulating factor
Vorinostat
Palifermin
Rituximab
U.S. FDA Resources
Further study details as provided by M.D. Anderson Cancer Center:
Primary Outcome Measures:
- 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.
| Estimated Enrollment: | 60 |
| Study Start Date: | August 2011 |
| Estimated Primary Completion Date: | August 2015 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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 on Days -12, -11, and -10.
|
Drug: Vorinostat
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: Alkeran
Procedure: 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: Rituxan
Drug: 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 on Days -12, -11, and -10. 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, +1 and +2.
Other Name: Kepivance
|
Show Detailed Description Eligibility| Ages Eligible for Study: | 12 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Age 12 to 65 years
- Patients with primary refractory or recurrent NHL or HL that do not qualify for treatment protocols of higher priority.
- Patients with double-hit NHL, in any state of the disease.
- Adequate renal function, as defined by estimated serum creatinine clearance >/=50 ml/min and/or serum creatinine </= 1.8 mg/dL.
- Adequate hepatic function, as defined by SGOT and/or SGPT </= 3 x upper limit of normal; serum bilirubin and alkaline phosphatase </= 2 x upper limit of normal.
- Adequate pulmonary function with FEV1, FVC and DLCO >/= 50% of expected corrected for hemoglobin.
- Adequate cardiac function with left ventricular ejection fraction >/= 40%. No uncontrolled arrhythmias or symptomatic cardiac disease.
- Zubrod performance status <2.
- Negative Beta HCG text in a woman with child-bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization
Exclusion Criteria:
- Patients with grade >/= 3 non-hematologic toxicity from previous therapy that has not resolved to </= grade 1.
- Patients with prior whole brain irradiation
- Patients with active hepatitis B, either active carrier (HBsAg +) or viremic (HBV DNA >/=10,000 copies/mL, or >/= 2,000 IU/mL).
- Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic hepatitis C or positive hepatitis C serology.
- Active infection requiring parenteral antibiotics
- HIV infection, unless the patient is receiving effective antiretroviral therapy with undetectable viral load and normal CD4 counts
- Patients having received radiation therapy in the month prior to enrollment.
- Patients with a cQT longer than 500 ms
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01421173
Contacts
| Contact: Yago Nieto, MD,PHD | 713-563-7508 |
Locations
| United States, Texas | |
| UT MD Anderson Cancer Center | Recruiting |
| Houston, Texas, United States, 77030 | |
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
| Principal Investigator: | Yago Nieto, MD,PHD | UT MD Anderson Cancer Center |
More Information
Additional Information:
No publications provided
| Responsible Party: | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT01421173 History of Changes |
| Other Study ID Numbers: | 2011-0407 |
| Study First Received: | August 18, 2011 |
| Last Updated: | May 2, 2013 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by M.D. Anderson Cancer Center:
|
Lymphoma Lymphoid malignancies Relapsed Refractory Autologous hematopoietic cell support Stem cell infusion Hodgkin's lymphoma non-Hodgkin's lymphoma Vorinostat SAHA Suberoylanilide Hydroxamic Acid MSK-390 Zolinza Busulfan Busulfex |
Myleran Gemcitabine Gemcitabine Hydrochloride Gemzar Melphalan Alkeran Rituximab Rituxan Dexamethasone Decadron G-CSF Filgrastim NeupogenTM Palifermin Kepivance |
Additional relevant MeSH terms:
|
Neoplasms Lymphoma Neoplasms by Histologic Type Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Busulfan Melphalan Gemcitabine Rituximab Vorinostat Lenograstim Immunosuppressive Agents Immunologic Factors |
Physiological Effects of Drugs Pharmacologic Actions Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Therapeutic Uses Myeloablative Agonists Antimetabolites, Antineoplastic Antimetabolites Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Radiation-Sensitizing Agents Adjuvants, Immunologic |
ClinicalTrials.gov processed this record on May 19, 2013