Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Lymphoma

Sclerosis

Hodgkin Disease

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Hodgkin Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Carboplatin

Etoposide

Ifosfamide

Bortezomib

Etoposide phosphate

Isophosphamide mustard

Mesna

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Bortezomib + ICE (Ifosfamide, Carboplatin, Etoposide):

Bortezomib 1.0 mg/m\^2 intravenous (IV) over 5 Seconds on Days 1 and 4; + ICE (Ifosfamide 5 Gm/m\^2 IV continuous infusion on Day 1, Carboplatin 5 AUC IV over 1 Hour Day 1, Etoposide 100 mg/m\^2 IV over 2 Hours Days 1-3) + Mesna 5 mg/m\^2 IV continuous infusion Day 1; 2 Gm/m\^2 IV continuous infusion over 12 Hours.

1.0 mg/m\^2 by Vein Over 5 Seconds on Days 1 and 4

100 mg/m\^2 By Vein Over 2 Hours On Days 1-3

5 Gm/m\^2 By Vein Continuous Infusion Over 24 Hours On Day 1

5 mg/m\^2 IV continuous Infusion over 24 Hours On Day 1; 2 Gm/m\^2 IV continuous infusion over 12 hours starting after completion of Ifosfamide + Mesna 24 hour continuous infusion

Michelle A. Fanale, MD

Primary Objectives:

1. To determine the toxicity profile of multiple doses of bortezomib when given with ICE in patients with relapsed and refractory classical Hodgkin lymphoma (HL).
2. To determine the maximum tolerated dose (MTD) of bortezomib when given in combination with ICE chemotherapy in patients with relapsed and refractory classical Hodgkin lymphoma (HL).

Secondary Objectives:

- To determine the overall response rate and complete response rate in patients with relapsed and refractory classical Hodgkin lymphoma (HL).

Bortezomib is designed to block a protein that plays a role in cell function and growth, which may cause cancer cells to die.

ICE is a combination of chemotherapy drugs that, together, may work more effectively at causing cancer cells to die by stopping cells from dividing.

Mesna is a drug that protects bladder cells from damage by the chemotherapy drug ifosfamide. It is used to decrease the risk of bleeding in the bladder.

Before you can start taking the drugs on this study, you will have "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. These tests may be performed within 28 days of starting the study drugs. If you have had some of these exams, tests, or procedures performed recently, they may not need to be repeated. This will be for your study doctor to decide. You will have a physical exam, including measurement of your vital signs (blood pressure, heart rate, temperature, and breathing rate), height, and weight. You will have x-rays and a bone marrow biopsy to check the status of the disease. To collect a bone marrow biopsy, an area of the hip or chest bone is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle. You will have a computed tomography (CT) scan of your abdomen, chest, and pelvis and a positron emission tomography (PET) scan. Blood (about 2-3 tablespoons) will be drawn for routine tests. Women who are able to have children must have a negative blood (about 1 teaspoon) pregnancy test within 1 month before starting therapy on this study. Because taking part in this study requires that participants' ability to fight off infections be normal, you will have blood drawn (about 1-2 tablespoons) to be tested for HIV within 6 months before starting therapy on this study. If your HIV test results are found to be positive, you will not be able to take part in this study.

All participants will receive bortezomib as a fixed dose, which will not change unless any intolerable side effects occur. At the start of this study, 3 participants will be given a dose of bortezomib. If this dose does not cause intolerable side effects, the dose will be increased as new participants take part in this study. There will be a total of 3 groups (with 3-6 participants per group) entered at increasing dose levels. The dose of bortezomib you receive will depend on when you join this study.

If you are found to be eligible to take part in this study, you will receive bortezomib plus ICE by vein. You will receive bortezomib, on Days 1 and 4, over 5 seconds. The ICE regimen will be given as a continuous infusion over different times as follows. On Day 1, you will receive ifosfamide and mesna over 24 hours. On Day 2, you will receive mesna over 12 hours and carboplatin over 1 hour. On Days 1-3, you will receive etoposide over 2 hours. This schedule for bortezomib plus ICE is considered 1 cycle (2 weeks) and will be repeated every 14 days.

You may have 3-6 cycles of the study drugs, depending on your tolerance of the drugs and the status of the disease. If the disease gets worse or you experience any intolerable side effects, you will be taken off this study.

Blood (about 2-3 tablespoons) will be drawn once a week for routine tests. You will have a study visit before the start of each 2-week cycle. During these visits, you will have a brief questionnaire that will ask about specific side effects you might be experiencing. It should take about 5 minutes to complete this questionnaire.

After completing 3 cycles, you will return for CT scans, bone marrow biopsies (if they were positive for disease before you began on this study), and a PET scan to check the status of the disease.

After completing 3 cycles (if the disease did not worsen and intolerable side effects did not occur), you may continue on this study for 3 more cycles. During Cycles 4-6, you will have the same scans and blood tests as mentioned above.

After completing this study, for every 3-4 months on an indefinite basis, you will have follow-up visits. During these visits, you will have blood drawn (about 2-3 tablespoons) for routine tests. You will also have the same scans that were performed during the screening visit.

This is an investigational study. Bortezomib and ICE are FDA approved and commercially available. The combination of bortezomib plus ICE is considered investigational and authorized for use in research only.

Up to 18 patients will take part in this study. All will be enrolled at M. D. Anderson.

Velcade Plus ICE for Patients With Relapsed Classical Hodgkin Lymphoma

Phase-I Study of Bortezomib (VELCADE) Plus ICE (Ifosfamide, Carboplatin, Etoposide) for Patients With Relapsed Classical Hodgkin Lymphoma

MTD dose escalation stops either at the highest indicated dose of bortezomib (1.5 mg/m2), or when a Dose limiting toxicity (DLT) has been observed in at least one third of the patients at any dose level.

Millennium Pharmaceuticals, Inc.

M.D. Anderson Cancer Center

Antirheumatic Agents

Anti-Inflammatory Agents

Anti-Infective Agents

Gemcitabine

Vinorelbine

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Prednisone

Vincristine

Bleomycin

Vinblastine

Immunosuppressive Agents

Immunologic Factors

Antimetabolites

Anti-Bacterial Agents

Antibiotics, Antitubercular

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Tubulin Modulators

Antimitotic Agents

* Doxorubicin 25 mg/m2 IV w 1,3,5,7,9,11
* Vinblastine 6 mg/m2 IV w 1,3,5,7,9,11
* Cyclophosphamide 750 mg/m2 IV w 1, 5, 9
* Etoposide2 60 mg/mg2 x 2 IV w 3, 7,11
* Vincristine1 1.4 mg/m2 IV w 2,4,6,8,10,12 (cap @ 2mg)
* Bleomycin 5 u/m2 IV w 2,4,6,8,10,12
* Gemcitabine 1250 mg/m2 IV w 13,15,17,19
* Vinorelbine 25 mg/m2 IV w 13,15,17,19
* Prednisone 40 mg/m2 PO qod w 1-10, taper

Vincristine1 1.4 mg/m2 IV w 2,4,6,8,10,12 (cap @ 2mg)

Sandra J. Horning, MD

Patients with 3 or more adverse prognostic factors have a higher relapse rate. Significant anti-tumor activity in Hodgkin's lymphoma has been reported with two new drugs:gemcitabine and vinorelbine. The introduction of these new agents with their different mechanisms of action into the Stanford V regimen may increase effectiveness while maintaining a favorable toxicity profile with respect to fertility and a low risk of secondary leukemia. On this basis, we propose a new regimen, Stanford VI, for patients with bulky and advanced HD with 3 or more risk factors.

Patients will receive chemotherapy weekly for 19 weeks, alone or followed by irradiation as indicated per protocol guidelines.

* Doxorubicin 25 mg/m2 IV w 1,3,5,7,9,11
* Vinblastine 6 mg/m2 IV w 1,3,5,7,9,11
* Cyclophosphamide 750 mg/m2 IV w 1, 5, 9
* Etoposide2 60 mg/mg2 x 2 IV w 3, 7,11
* Vincristine1 1.4 mg/m2 IV w 2,4,6,8,10,12 (cap @ 2mg)
* Bleomycin 5 u/m2 IV w 2,4,6,8,10,12
* Gemcitabine 1250 mg/m2 IV w 13,15,17,19
* Vinorelbine 25 mg/m2 IV w 13,15,17,19
* Prednisone 40 mg/m2 PO qod w 1-10, taper

Combination Chemotherapy +/- Radiation in High Risk Hodgkin's Disease

A Phase II Trial of Stanford VI ± Radiation Therapy in Locally Extensive and Advanced Stage Hodgkin's Disease With 3+ Risk Factors: the G6 Study

National Cancer Institute (NCI)

Stanford University

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Velcade Plus ICE for Patients With Relapsed Classical Hodgkin Lymphoma	NCT00439361	Hodgkin Lymphom... Lymphoma	Bortezomib Carboplatin Etoposide Ifosfamide Mesna	16 Years -	M.D. Anderson Cancer Center
Combination Chemotherapy +/- Radiation in High Risk Hodgkin's Disease	NCT00225173	Hodgkin Disease	Doxorubicin Vinblastine Cyclophosphamid... Etoposide Vincristine Bleomycin Gemcitabine Vinorelbine Prednisone	18 Years - 70 Years	Stanford University

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