Clinical trial NCT00787527
Conditions: Lymphoma
Keywords: 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
Sponsor: M.D. Anderson Cancer Center
Start date: 2008-11-01; Completion date: 2012-12-01
Enrollment: 14 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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.

Detailed description:
The Study Drugs:

Vorinostat is designed to cause chemical changes in different groups of proteins that are attached to DNA (the genetic material of cells), which may slow the growth of cancer cells or cause the cancer cells to die.

Cyclophosphamide is designed to interfere with the multiplication of cancer cells, which may slow or stop their growth. This may cause the cancer cells to die.

Doxorubicin is designed to stop the growth of cancer cells, which may cause the cells to die.

Vincristine is designed to interfere with the multiplication of cancer cells, which may slow or stop their growth. This may cause the cancer cells to die.

Prednisone is designed to decrease inflammation by preventing white blood cells from completing an inflammatory reaction. This drug can cause lymphocytes, a type of white blood cell, to break apart and die.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will begin to take vorinostat on the first day of treatment which is Day -1. Vorinostat capsules are taken by mouth, either 3 times a day or 2 times a day, depending on what the study doctor thinks is in your best interest. If you are taking vorinostat 3 times a day, it should be taken in the morning, afternoon and evening. If you are taking vorinostat 2 times a day, you will take the capsules in the morning and evening. The capsules must be taken with food (within 30 minutes after a meal). You will receive the vorinostat capsules on the first day of each cycle. You will also receive instructions on how to take the drug. You should return any unused vorinostat capsules back to study staff at the end of each cycle. You will take vorinostat for 5 days (Days -1 through 3) of each cycle and then beginning on Day 1, cyclophosphamide, vincristine, and doxorubicin will be given though a needle in your vein. This will happen for each 21-day study cycle. Cyclophosphamide is given over 1 hour. Vincristine is given over 15 minutes. Doxorubicin is also given over 15 minutes.

The starting dose of vorinostat may change On Days 1-5 of each cycle, you will take prednisone tablets by mouth.

If you begin to experience severe or intolerable side effects, the study drug schedule may be stopped for up to 3 weeks. If the side effects improve, you may be able to receive the study drugs again, with either a lower dose of vorinostat or if you are taking vorinostat three times daily, you may take it twice a day instead. The chemotherapy drugs (cyclophosphamide, doxorubicin, vincristine, and prednisone) may also be lowered depending on what side effects are being experienced. If you continue to have severe or intolerable side effects with the lower dose of vorinostat and chemotherapy, you will taken off study.

Study Visits:

On Day 1 of all cycles, the following tests and procedures will be performed:

* Your medical history will be recorded, including any drugs that you are taking.
* You will be asked about any side effects you may have experienced.
* You will have a physical exam, including measurement of your vital signs and weight.
* Blood (about 5 teaspoons) will be drawn for routine tests.
* Your performance status will be recorded.

On Day 1 of Cycle 2 you will have an ECG.

On or before Day 1 of Cycle 3 the following tests and procedures will be performed if your doctor thinks necessary:

* You will have CT and/or PET scans to check the status of the disease.
* You may have a bone marrow aspirate and/or biopsy to check the status of the disease.

Length of Study:

You will receive the study drugs for up to 6 cycles. You may be taken off study early if the disease gets worse or if severe or intolerable side effects occur.

End-of-Study Visit:

If you go off study treatment for any reason, you will have an end-of-study visit within 4 weeks after your last dose of study drugs or before starting a new treatment. At this visit, the following tests and procedures will be performed:

* You will have a physical exam, including measurement of your vital signs.
* Your performance status will be recorded.
* You will be asked about any side effects you may have experienced.
* Blood (about 5 teaspoons) will be drawn for routine tests.
* You will have CT scans and PET scans to check the status of the disease.
* If you had skin lesions when you began the study, the skin lesions will be photographed.
* If the doctor thinks it is needed, you will have bone marrow biopsy and/or aspirate.

Follow-up Visits:

After you are off study treatment, you will have follow-up visits. You will go to these visits every 3 months for the1st year, every 4 months for the 2nd and 3rd years, and every 6 months for the 4th and 5th years. After this, you will return 1 time each year unless the lymphoma returns. The following tests and procedures will be performed:

* You will have a physical exam, including measurement of your vital signs.
* Your performance status will be recorded
* You will be asked about any side effects you may have experienced.
* Blood (about 5 teaspoons) will be drawn for routine tests.
* You will have CT scans and PET scans to check the status of the disease.
* If you had skin lesions when you began the study, the skin lesions will be photographed.
* If the doctor thinks it is needed, you will have bone marrow biopsy and/or aspirate.

This is an investigational study. Vorinostat is FDA approved and commercially available for the treatment of cutaneous T-cell lymphoma that has not come back or not responded to prior therapy. CHOP is currently FDA approved for treatment of patients with NHL. The use of vorinostat in combination with CHOP in patients with T-cell NHL is investigational.

Up to 52 patients will take part in this study. All will be enrolled at MD Anderson.

Arms: arm 1: Zolinza (vorinostat) + CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)
Interventions: intervention 1: Zolinza (vorinostat) intervention 2: Cyclophosphamide intervention 3: Doxorubicin intervention 4: Vincristine intervention 5: Prednisone
Intervention descriptions: intervention 1: 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. intervention 2: 750 mg/m\^2 by vein over 1 hour on Day 1 of 21 day cycle intervention 3: 50 mg/m\^2 by vein over 15 minutes on Day 1 of 21 day cycle intervention 4: 1.4 mg/m\^2 by vein over 15 minutes on Day 1 of 21 day cycle intervention 5: 100 mg tablets by mouth once a day on Days 1-5 of 21 day cycle

Protocol documents: