Vorinostat With Gemcitabine, Busulfan, and Melphalan With Stem Cell Transplant (SCT) in Relapsed or Refractory Lymphoid Malignancies - Full Text View

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 Drug: Dexamethasone acetate	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:

MedlinePlus related topics: Cancer

Drug Information available for: Dexamethasone Busulfan Melphalan Dexamethasone sodium phosphate Melphalan hydrochloride Dexamethasone acetate Gemcitabine Filgrastim Gemcitabine hydrochloride Vorinostat Palifermin Rituximab

Genetic and Rare Diseases Information Center resources: Hodgkin Lymphoma Lymphosarcoma

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:	80
Study Start Date:	August 2011
Estimated Primary Completion Date:	August 2016 (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 for 6 doses starting on Day 0. Dexamethasone 8 mg by vein twice a day from day -8 AM to day -2 PM.	Drug: Vorinostat Starting dose: 200 mg by mouth on Days -8 to -2. Other Names: SAHA Suberoylanilide Hydroxamic Acid MSK-390 Zolinza 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: Gemcitabine Hydrochloride Gemzar 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: Busulfex Myleran 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: Filgrastim NeupogenTM 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

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 for 6 doses starting on Day 0. Dexamethasone 8 mg by vein twice a day from day -8 AM to day -2 PM.

Drug: Vorinostat

Starting dose: 200 mg by mouth on Days -8 to -2.

Other Names:

SAHA
Suberoylanilide Hydroxamic Acid
MSK-390
Zolinza

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:

Gemcitabine Hydrochloride
Gemzar

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:

Busulfex
Myleran

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:

Filgrastim
NeupogenTM

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

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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.
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 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01421173

Locations


United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Investigators


Principal Investigator:	Yago Nieto, MD,PHD	M.D. Anderson Cancer Center

More Information

Additional Information:

UT MD Anderson Website This link exits the ClinicalTrials.gov site

No publications provided


Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT01421173 History of Changes
Other Study ID Numbers:	2011-0407, NCI-2011-02891
Study First Received:	August 18, 2011
Last Updated:	November 5, 2014
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:


Busulfan Dexamethasone Dexamethasone acetate Gemcitabine Melphalan Vorinostat Alkylating Agents Anti-Infective Agents Anti-Inflammatory Agents Antiemetics Antimetabolites Antimetabolites, Antineoplastic Antineoplastic Agents Antineoplastic Agents, Alkylating Antineoplastic Agents, Hormonal	Antiviral Agents Autonomic Agents Central Nervous System Agents Enzyme Inhibitors Gastrointestinal Agents Glucocorticoids Histone Deacetylase Inhibitors Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Immunologic Factors Immunosuppressive Agents Molecular Mechanisms of Pharmacological Action Myeloablative Agonists Peripheral Nervous System Agents Pharmacologic Actions

ClinicalTrials.gov processed this record on March 03, 2015