Vorinostat With Gemcitabine, Busulfan, and Melphalan With Stem Cell Transplant (SCT) in Relapsed or Refractory Lymphoid Malignancies
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| ClinicalTrials.gov Identifier: NCT01421173 |
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Recruitment Status :
Completed
First Posted : August 22, 2011
Last Update Posted : November 18, 2015
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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) |
| 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 |
| Study Start Date : | August 2011 |
| Actual Primary Completion Date : | September 2015 |
| Actual Study Completion Date : | September 2015 |
| Arm | Intervention/treatment |
|---|---|
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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.
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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 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. 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 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.
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| Ages Eligible for Study: | 12 Years to 65 Years (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Age 12 to 65 years
- Patients with primary refractory or recurrent non-Hodgkin's lymphoma (NHL) or HL that do not qualify for treatment protocols of higher priority.
- Patients with double-hit NHL, in any state of the disease.
- Patients with peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) in any state of the disease.
- Angioimmunoblastic T-cell lymphoma (AITL) in any stage 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 serum glutamate oxaloacetate transaminase (SGOT) and/or serum glutamate pyruvate transaminase (SGPT) </= 3 x upper limit of normal; serum bilirubin and alkaline phosphatase </= 2 x upper limit of normal.
- Adequate pulmonary function with forced expiratory volume at one second (FEV1), forced vital capacity (FVC) and diffusing capacity of lung for carbon monoxide (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 diffusing capacity of lung for carbon monoxide (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 cluster of differentiation 4 (CD4) counts
- Patients having received radiation therapy in the month prior to enrollment.
- Patients with a cQT longer than 500 ms
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): 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 |
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT01421173 History of Changes |
| Other Study ID Numbers: |
2011-0407 NCI-2011-02891 ( Registry Identifier: NCI CTRP ) |
| First Posted: | August 22, 2011 Key Record Dates |
| Last Update Posted: | November 18, 2015 |
| Last Verified: | November 2015 |
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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 |
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Lymphoma Neoplasms Neoplasms by Histologic Type Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Gemcitabine Dexamethasone Dexamethasone acetate Rituximab Melphalan Busulfan Vorinostat BB 1101 |
Lenograstim Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Antineoplastic Agents Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |