A Phase I/II of Vorinostat plus CHOP in untreated T-cell non-Hodgkin's Lymphoma
The goal of this clinical research study is to find out how well the drug Zolinza (vorinostat) works in combination with the drug combination called CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) to treat patients with untreated T-cell NHL. The safety of these drugs in combination and the best dose of vorinostat when given in combination with CHOP will also be studied.
Disease Group: Lymphoma
Treatment Agent: Cyclophosphamide,Doxorubicin,Prednisone,Vincristine,Vorinostat
Treatment Location: Only at MD Anderson
Estimatated Length of Stay in Houston: Pts will receive CHOP on day 1 of every cycle; Cycles will be repeated every 21 ;days.;Up to two capsules of vorinostat are to be administered orally twice daily(in ;am and pm) in repeated 21-day cycles consisting of 10 days dosing starting on ;days 5-14
Return Visit: Days 5 through 14 of each cycle.
Home Care: NA
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.
IRB Review and Approval Date: 04/03/2009
Recruitment Status: Not Accepting
Projected Accrual: N/A
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 biopsy proven disease which can include bone marrow and/or lymph node (cutnaneous only disease is excluded)
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) There is Patients are required to have adequate bone marrow reserve as indicated: Absolute neutrophil count (ANC) >/= 1000/mm^3, Platelets >/= 50,000/mm3, Hemoglobin >/= 8g/dL. If there is bone marrow involvement by lymphoma then there is no minimum level of counts required.
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 are being used for symptom management and not for treatment of lymphoma.
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.
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.
Information and next steps
Phase I/Phase II
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