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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01421173
First received: August 18, 2011
Last updated: January 3, 2014
Last verified: January 2014
  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:


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 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 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

  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:

  1. Age 12 to 65 years
  2. Patients with primary refractory or recurrent NHL or HL that do not qualify for treatment protocols of higher priority.
  3. Patients with double-hit NHL, in any state of the disease.
  4. Patients with peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) in any state of the disease.
  5. Angioimmunoblastic T-cell lymphoma (AITL) in any stage of the disease.
  6. Adequate renal function, as defined by estimated serum creatinine clearance >/=50 ml/min and/or serum creatinine </= 1.8 mg/dL.
  7. 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.
  8. Adequate pulmonary function with FEV1, FVC and DLCO >/= 50% of expected corrected for hemoglobin.
  9. Adequate cardiac function with left ventricular ejection fraction >/= 40%. No uncontrolled arrhythmias or symptomatic cardiac disease.
  10. Zubrod performance status <2.
  11. 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:

  1. Patients with grade >/= 3 non-hematologic toxicity from previous therapy that has not resolved to </= grade 1.
  2. Patients with prior whole brain irradiation
  3. Patients with active hepatitis B, either active carrier (HBsAg +) or viremic (HBV DNA >/=10,000 copies/mL, or >/= 2,000 IU/mL).
  4. Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic hepatitis C or positive hepatitis C serology.
  5. Active infection requiring parenteral antibiotics
  6. HIV infection, unless the patient is receiving effective antiretroviral therapy with undetectable viral load and normal CD4 counts
  7. Patients having received radiation therapy in the month prior to enrollment.
  8. 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
UT MD Anderson Cancer Center
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: January 3, 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:
Neoplasms
Lymphoma
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Gemcitabine
BB 1101
Vorinostat
Busulfan
Melphalan
Rituximab
Dexamethasone
Dexamethasone acetate
Dexamethasone 21-phosphate
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on September 22, 2014