SAHA + CHOP in Untreated T-cell Non-Hodgkin's Lymphoma

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00787527
First received: November 6, 2008
Last updated: September 2, 2014
Last verified: September 2014
  Purpose

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 Non-Hodgkin's Lymphoma (NHL). The safety of these drugs in combination and the best dose of vorinostat when given in combination with CHOP will also be studied.


Condition Intervention Phase
Lymphoma
Drug: Zolinza (vorinostat)
Drug: Cyclophosphamide
Drug: Doxorubicin
Drug: Vincristine
Drug: Prednisone
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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:
  • Phase I Maximum Tolerated Dose (MTD) of Vorinostat [ Time Frame: 21 Days ] [ Designated as safety issue: Yes ]
    MTD of Vorinostat when administered in combination with Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (CHOP) defined as highest dose level in which 6 patients have been treated with less than 2 instances of dose limiting toxicity (DLT). Continual reassessment during each 21-day cycle to assess dose limiting toxicity. Two schedules of Vorinostat were investigated: Phase I A) daily doses on days 5 to 14, or Phase II B) three times a day on days -2 to 3 of standard CHOP every 21 days. Vorinostat was administered orally on days 5 to 14 (Schedule A), first at 300 mg orally once daily (total doses of 3000 mg over 10 days per cycle), and next at 200 mg orally twice daily (total doses of 4000 mg over 10 days per cycle); and for Phase II Schedule B Vorinostat administered orally 300 mg orally three times daily from days -2 to 3 (4500 mg over 5 days per cycle).

  • Number of Participants With Dose Limiting Toxicity for Determination Phase I (Schedule A) MTD of Vorinostat [ Time Frame: 21 Days ] [ Designated as safety issue: Yes ]
    MTD of Vorinostat defined as highest dose level in which 6 patients have been treated with less than 2 instances of DLT. Continual reassessment during each 21-day cycle to assess DLT. Vorinostat was administered orally on days 5 to 14 (Schedule A), first at 300 mg orally once daily (total doses of 3000 mg over 10 days per cycle), and next at 200 mg orally twice daily (total doses of 4000 mg over 10 days per cycle. The dose of Vorinostat escalated in successive 3+3 cohorts of participants to determine the MTD.

  • Phase II MTD of Vorinostat [ Time Frame: 21 Days ] [ Designated as safety issue: Yes ]
    MTD of Vorinostat when administered in combination with Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (CHOP) defined as highest dose level in which 6 patients have been treated with less than 2 instances of dose limiting toxicity (DLT). Continual reassessment during each 21-day cycle to assess dose limiting toxicity. Two schedules of Vorinostat were investigated: Phase I A) daily doses on days 5 to 14, or Phase II B) three times a day on days -2 to 3 of standard CHOP every 21 days. Vorinostat was administered orally on days 5 to 14 (Schedule A), first at 300 mg orally once daily (total doses of 3000 mg over 10 days per cycle), and next at 200 mg orally twice daily (total doses of 4000 mg over 10 days per cycle); Schedule B Vorinostat administered orally 300 mg orally three times daily from days -2 to 3 (4500 mg over 5 days per cycle).


Enrollment: 14
Study Start Date: November 2008
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Zolinza + CHOP
Zolinza (vorinostat) + CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)
Drug: Zolinza (vorinostat)
Up to two 100 mg capsules of Vorinostat (dosage will vary from 100 mg orally (PO) twice daily (BID), 300 mg PO every evening and 200 mg PO BID with the starting dose at 300 mg PO every evening for the phase I trial) are to be administered orally twice daily (once in the morning and once in the evening, or if in the daily dosing cohort once in the evening) in repeated 21-day cycles consisting of 10 days dosing starting on days 5 through 14 followed by a 7-day rest period, during which no vorinostat will be administered.
Other Names:
  • vorinostat
  • SAHA
  • Suberoylanilide Hydroxamic Acid
  • MSK-390
Drug: Cyclophosphamide
750 mg/m^2 by vein over 1 hour on Day 1 of 21 day cycle
Other Names:
  • Cytoxan
  • Neosar
Drug: Doxorubicin
50 mg/m^2 by vein over 15 minutes on Day 1 of 21 day cycle
Other Names:
  • AD
  • Hydroxydaunomycin hydrochloride
Drug: Vincristine
1.4 mg/m^2 by vein 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) (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 (cutaneous 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 human chorionic gonadotropin (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/Natural Killer (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 histone deacetylase (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 central nervous system (CNS) lymphoma.
  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: NCT00787527

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Yasuhiro Oki, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00787527     History of Changes
Other Study ID Numbers: 2008-0484
Study First Received: November 6, 2008
Results First Received: September 2, 2014
Last Updated: September 2, 2014
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:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Prednisone
Vincristine
Vorinostat
Alkylating Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Enzyme Inhibitors
Glucocorticoids
Histone Deacetylase Inhibitors
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors

ClinicalTrials.gov processed this record on October 20, 2014