Full Text View
Tabular View
No Study Results Posted
Related Studies
SAHA + CHOP in Untreated T-cell Non-Hodgkin's Lymphoma
This study is currently recruiting participants.
Verified by M.D. Anderson Cancer Center, October 2009
First Received: November 6, 2008   Last Updated: October 6, 2009   History of Changes
Sponsor: M.D. Anderson Cancer Center
Collaborator: Merck
Information provided by: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00787527
  Purpose

Primary Objectives:

Phase I

  1. Determine the toxicity profile and the maximum tolerated dose (MTD) of vorinostat when administered in combination with Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (CHOP)

    Phase II

  2. To evaluate the progression free survival for patients with T-cell NHL receiving the combination of vorinostat and CHOP

Secondary Objectives (Phase I and II):

  1. To evaluate the response rate for patients with T-cell NHL receiving the combination of vorinostat and CHOP
  2. To assess overall survival in patients with T-cell NHL treated with the combination of vorinostat and CHOP.
  3. Correlative studies will be done to assess the role of vorinostat mediated apoptosis in combination with cytotoxic chemotherapy. Changes in marker expression from baseline to post treatment will be correlated with patient clinical response.
  4. Correlative studies will be done to assess cytokine, gene, and protein array signatures for the various subsets of T-cell NHL.

Condition Intervention Phase
Lymphoma
Drug: Zolinza (vorinostat)
Drug: Cyclophosphamide
Drug: Doxorubicin
Drug: Vincristine
Drug: Prednisone
Phase I
Phase II

Study Type: Interventional
Study Design: Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title: A Phase I/II of Vorinostat Plus CHOP in Untreated T-cell Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) of vorinostat [ Time Frame: Continual reassessment during each 21-day cycle to assess dose limiting toxicity ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 52
Study Start Date: November 2008
Estimated Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
Zolinza (vorinostat) + CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)
Drug: Zolinza (vorinostat)
Starting dose of 100 mg capsules by mouth twice daily on Days 5-14 of 21 day cycle
Drug: Cyclophosphamide
750 mg/m^2 by vien over 1 hour on Day 1 of 21 day cycle
Drug: Doxorubicin
50 mg/m^2 by vien over 15 minutes on Day 1 of 21 day cycle
Drug: Vincristine
1.4 mg/m^2 by vien over 15 minutes on Day 1 of 21 day cycle
Drug: Prednisone
100 mg tablets by mouth once a day on Days 1-5 of 21 day cycle

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must have a new diagnosis of T-cell NHL eligible histologies include:Peripheral T-cell lymphoma (unspecified), CD 30 + anaplastic large cell lymphoma ( ALK-1 positive and ALK-1 negative), angioimmunoblastic T-cell lymphoma, intestinal T-cell lymphoma, subcutaneous panniculitic T-cell lymphoma.
  2. Patients who are eligible for blood and marrow transplant can receive this treatment to maximal reduction of tumor bulk. A minimum of four cycles of therapy will be given before evaluation for to hematopoetic stem cell transplant.
  3. Patients must have at least one clear-cut bi-dimensionally measurable site (> 10mm by spiral computerized tomography - CT - scan or > 20mm by conventional measures). Baseline measurements of measurable sites and evaluation of evaluable disease must be obtained within four weeks prior to registration of this study.
  4. Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
  5. Patients must be age 18 years old and above.There is no dosing or adverse event data are currently available on the use of vorinostat in patients <18 years of age, children are excluded from this study but may be eligible for future pediatric phase 2 combination trials.
  6. Patients are required to have adequate bone marrow reserve as indicated: Absolute neutrophil count (ANC) >/= 1000/mm^3, Platelets >/= 80,000/mm^3, Hemoglobin >/= 8g/dL. If there is bone marrow involvement by lymphoma then there is no minimum level of counts required. These values must be obtained within two weeks before protocol entry.
  7. Patients must have adequate liver function as indicated by: Bilirubin </= 1.5 times the upper limit of normal (ULN), Alanine transaminase (ALT) </=2 times the (ULN) or aspartate transaminase (AST) </= 2 times the ULN. These values must be obtained within two weeks before protocol entry.
  8. Patients are required to have adequate renal function as indicated by a serum creatinine </= 2.5 mg/dL. This value must be obtained within two weeks before protocol entry.
  9. Left ventricular ejection fraction must be evaluated by nuclear medicine scan or echocardiography and measure >/= 50%.
  10. Concomitant steroids may continue provided they have been on a stable dosage for at least 3 months prior to enrollment. Patients may continue to receive systemic corticosteroids as premedications for chemotherapy, antibiotics, and transfusions.
  11. Male patients must agree to use a barrier method of contraception or agree to abstain from heterosexual activity for the duration of the study
  12. Female patients must be willing to use two adequate barrier methods of contraception to prevent pregnancy or agree to abstain from heterosexual activity throughout the study or be post menopausal (free from menses > two years or surgically sterilized).
  13. Female patients of childbearing potential must have a negative serum pregnancy test (Beta hCG) within 72 hours of receiving the first dose of vorinostat.
  14. Patients must have the ability able to give informed consent.

Exclusion Criteria:

  1. 1. Patients with a) T-cell lymphoma with skin involvement only are excluded if they have no evidence of systemic disease b)T-cell prolymphocytic leukemia (T-PLL) c) T-cell large granular lymphocytic leukemia d) Primary cutaneous CD30+ disorders: anaplastic large cell lymphoma and lymphomatoid papulosis e) Angiocentric/nasal type T/NK-cell lymphoma f) Hepatosplenic gamma-delta T-cell lymphoma
  2. Patients with active Hepatitis B and/or Hepatitis C infection.
  3. Patients with known HIV infection are excluded. a) These patients are excluded secondary to potential to target activated T-cells, in a population of patients already at risk for T-cell depletion, would be a contraindication to therapy.
  4. Patients with active infections requiring specific anti-infective therapy are not eligible until all signs of infections are resolved.
  5. Patients with pre-existing cardiovascular disease requiring ongoing treatment. This includes:a) Congestive heart failure, b) Severe CAD, c) Cardiomyopathy, d) Uncontrolled cardiac arrhythmia, e) Unstable angina pectoris, f) Recent MI (within 6 months).
  6. Patients with prior exposure to either vorinostat (including other HDAC inhibitors except valproic acid) or anthracyclines: a) Patients who have received valproic acid (VPA) for the treatment of seizures may be enrolled on this study, but must not have received VPA within 30 days of study enrollment.
  7. Patients who are pregnant or breast-feeding. a)Effects of this treatment on the fetus and young children are unknown at this time.
  8. Patients who have had an invasive solid tumor malignancy in the past five years except non-melanoma skin cancers or cervical carcinoma in situ or ductal/lobular carcinoma in situ of the breast who is currently without evidence of disease.
  9. Patients undergoing anti-neoplastic chemotherapy, radiation, hormonal (excluding contraceptives) or immunotherapy, or investigational medications within the past four weeks.
  10. Patients with deep vein thrombosis within three months.
  11. Patient with concurrent use of complementary or alternative medicines.
  12. Patients with psychiatric illness and/or social situations that would limit compliance with the study medication and requirements.
  13. Patients with grade 2 or more neuropathy.
  14. Patients with known CNS lymphoma.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00787527

Contacts
Contact: Barbara Pro, MD 713-792-2860

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Barbara Pro, MD            
Sponsors and Collaborators
M.D. Anderson Cancer Center
Merck
Investigators
Principal Investigator: Barbara Pro, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: UT MD Anderson Cancer Center ( Barbara Pro, MD/Associate Professor )
Study ID Numbers: 2008-0484
Study First Received: November 6, 2008
Last Updated: October 6, 2009
ClinicalTrials.gov Identifier: NCT00787527     History of Changes
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Lymphoma
Non-Hodgkin's Lymphoma
SAHA
Vorinostat
Suberoylanilide Hydroxamic Acid
MSK-390
CHOP
Cyclophosphamide
Doxorubicin
AD
Hydroxydaunomycin hydrochloride
Cytoxan
Neosar
Vincristine
Prednisone
Untreated T-cell
T-cell NHL
Peripheral T-cell lymphoma
PTCL
CD 30
Anaplastic large cell lymphoma
Angioimmunoblastic T-cell lymphoma
Intestinal T-cell lymphoma
Subcutaneous panniculitic T-cell lymphoma

Additional relevant MeSH terms:
Anticarcinogenic Agents
Anti-Inflammatory Agents
Prednisone
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Cyclophosphamide
Antibiotics, Antineoplastic
Hormones
Sensory System Agents
Lymphoma, T-Cell
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Lymphoma
Alkylating Agents
Immunoproliferative Disorders
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Mitosis Modulators
Vorinostat
Vincristine
Enzyme Inhibitors
Antimitotic Agents
Protective Agents
Glucocorticoids
Immunosuppressive Agents

ClinicalTrials.gov processed this record on November 20, 2009