Bortezomib Plus ICE (BICE) Versus Standard ICE for Patients With Relapsed/Refractory Classical Hodgkin Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00967369
First received: August 25, 2009
Last updated: February 14, 2014
Last verified: February 2014
  Purpose

The goal of this clinical research study is to learn if bortezomib when given in combination with ifosfamide, carboplatin, and etoposide (a routine chemotherapy combination called ICE) can help to control Hodgkin's lymphoma better than ICE when given alone. The safety of this drug combination will also be studied.


Condition Intervention Phase
Hodgkin's Lymphoma
Drug: Bortezomib
Drug: Ifosfamide
Drug: Carboplatin
Drug: Etoposide
Drug: Neulasta (Pegfilgrastim)
Drug: Mesna
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study of Bortezomib Plus ICE (BICE) Versus Standard ICE for Patients With Relapsed/Refractory Classical Hodgkin Lymphoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Complete Remission [ Time Frame: Evaluated for response after 0.75 months after receiving treatment for 3 cycles (21 days per cycle). ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: August 2009
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: B-ICE
B-ICE = Bortezomib + Ifosfamide, Carboplatin, and Etoposide (a routine chemotherapy combination)
Drug: Bortezomib
1.5 mg/m^2 by vein over 5 seconds on Days 1 and 4 of each cycle.
Other Names:
  • Velcade
  • LDP-341
  • MLN341
  • PS-341
Drug: Ifosfamide
5 gm/m^2 by vein over 24 hours on Day 1 of each cycle. With Ifosfamide, receive Mesna 5 gm/m^2 by vein over 24 hours.
Other Name: Ifex
Drug: Carboplatin
Maximum of 800 mg by vein over 1 hour on Day 1 of each cycle.
Other Name: Paraplatin
Drug: Etoposide
100 mg/m^2 by vein over 2 hours each day on Days 1-3 of each cycle.
Other Name: VePesid
Drug: Neulasta (Pegfilgrastim)
6 mg through a needle under the skin on Day 5 (If you are in Group 1) or Day 4 (if you are in Group 2) of each cycle.
Other Name: PEG-G-CSF
Drug: Mesna
2 gm/m2 by vein over 12 hours on Day 2 to start day after Ifosfamide + Mesna.
Other Name: Mesnex
Experimental: ICE
ICE = Ifosfamide, Carboplatin, and Etoposide (a routine chemotherapy combination)
Drug: Ifosfamide
5 gm/m^2 by vein over 24 hours on Day 1 of each cycle. With Ifosfamide, receive Mesna 5 gm/m^2 by vein over 24 hours.
Other Name: Ifex
Drug: Carboplatin
Maximum of 800 mg by vein over 1 hour on Day 1 of each cycle.
Other Name: Paraplatin
Drug: Etoposide
100 mg/m^2 by vein over 2 hours each day on Days 1-3 of each cycle.
Other Name: VePesid
Drug: Neulasta (Pegfilgrastim)
6 mg through a needle under the skin on Day 5 (If you are in Group 1) or Day 4 (if you are in Group 2) of each cycle.
Other Name: PEG-G-CSF
Drug: Mesna
2 gm/m2 by vein over 12 hours on Day 2 to start day after Ifosfamide + Mesna.
Other Name: Mesnex

  Hide Detailed Description

Detailed Description:

The Study Drugs:

Ifosfamide is designed to slow or stop the growth of cancer cells.

Carboplatin is designed to interfere with the growth of cancer cells by stopping cell division, which may cause the cells to die.

Etoposide is designed to block cell growth.

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

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 groups:

  • If you are in Group 1, you will receive bortezomib and ICE.
  • If you are in Group 2, you will receive ICE only.

If you are one of the first 20 patients enrolled in this study, you will have an equal chance of being assigned to either group. If you join the study after 20 patients have been enrolled, you will have a higher chance of being assigned to the group that has been shown to be more effective.

Study Drug Administration:

Every "study cycle" will be made up of about 2 weeks. Cycles may need to be longer to allow for recovery.

You will need to stay in the hospital while you are receiving the study drugs. If you are in Group 1, you will need to be in the hospital for 5-7 days for this. If you are in Group 2, you will need to be in the hospital for 4-6 days for this.

You will receive ifosfamide by vein over 24 hours on Day 1 of each cycle. When you begin receiving ifosfamide, you will also begin receiving mesna by vein over 36 hours. Mesna is a drug that helps to protect the bladder from damage by ifosfamide.

You will receive carboplatin by vein over 1 hour on Day 1 of each cycle.

You will receive etoposide by vein over 2 hours each day on Days 1-3 of each cycle.

You will receive Neulasta (pegfilgrastim) through a needle under the skin on Day 5 (If you are in Group 1) or Day 4 (if you are in Group 2) of each cycle. Pegfilgrastim is a drug that helps low white blood cell counts return to normal levels.

If you are in Group 1, you will also receive bortezomib by vein over 5 seconds on Days 1 and 4 of each cycle.

Study Visits:

At all study visits, you will be asked about any other drugs that you may be taking and about any side effects that you may be experiencing.

Within 3 days of each cycle, the following tests and procedures will be performed:

  • You will have a physical exam.
  • Blood (about 2 teaspoons) will be drawn for routine tests.
  • You will have a chest x-ray and CT scans to check the status of the disease (Cycle 1 only).

On each day that you receive study drugs, blood (about 2 teaspoons each time) will be drawn for routine tests.

One (1) time each week, blood (about 2 teaspoons) will be drawn for routine tests.

On Day 21 (+/- 7 days) of Cycle 3, the following tests and procedures will be performed:

  • You will have a physical exam.
  • Blood (about 2 teaspoons) will be drawn for routine tests.
  • You will have a chest x-ray to check the status of the disease.
  • You will have CT scans of the neck, chest, abdomen, and pelvis to check the status of the disease.
  • You will have a PET/CT scan to check the status of the disease.
  • You will have a bone marrow biopsy to check the status of the disease.

If you are found to be eligible to have a stem cell transplant after this visit, you will be taken off study. Your doctor will describe this procedure to you and you will sign a separate consent form.

Length of Study:

You can receive the study drugs for up to 6 cycles. You will be taken off study if you have intolerable side effects or if the disease gets worse.

End-of-Treatment Visit:

After you have finished receiving the study drugs for any reason, you will have an end-of-treatment visit. At the end-of-treatment visit, the following tests and procedures will be performed:

  • You will have a physical exam.
  • Blood (about 2 teaspoons) will be drawn for routine tests.
  • You will have a chest x-ray to check the status of the disease.
  • You will have CT scans of the neck, chest, abdomen, and pelvis to check the status of the disease.
  • You will have a PET/CT scan to check the status of the disease.
  • If your doctor thinks it is needed, you will have a bone marrow biopsy to check the status of the disease.

Follow-Up Visits:

After the end-of-treatment visit, you will have follow-up visits every 4 months for 2 years. The following tests and procedures will be performed:

  • You will have a physical exam.
  • Blood (about 2 teaspoons) will be drawn for routine tests.
  • You will have a chest x-ray to check the status of the disease.
  • You will have CT scans of the neck, chest, abdomen, and pelvis to check the status of the disease.

This is an investigational study. Bortezomib is FDA approved and commercially available for the treatment of mantle cell lymphoma and myeloma. ICE is FDA approved and commercially available for the treatment of several types of lymphoma, including relapsed and refractory Hodgkins lymphoma. The combination of bortezomib and ICE for the treatment of Hodgkin's lymphoma is investigational.

Up to 50 patients will take part in this study. All will be enrolled at MD Anderson.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Relapsed or refractory classical Hodgkin lymphoma
  2. Patients must have received a front-line standard anthracycline- containing regimen, such as ABVD, Stanford V, or BEACOPP.
  3. Bi-dimensionally measurable disease with at least 1 lesion >= 2.0 cm in a single dimension.
  4. Patients must meet the following required baseline laboratory data: a) absolute neutrophil count (ANC) >= 1,500/microL, b) platelet count >= 100,000/ microL, c) hemoglobin >= 8 g/dL, d) serum bilirubin < 2.0 mg/dL, e) alkaline phosphatase < 2 x upper limits of normal (ULN), f) AST and ALT < 2 x ULN, g) serum creatinine <= 1.5 mg/dL.
  5. Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2.
  6. Age >= 16 years.
  7. Females of childbearing potential must have a negative serum beta-hCG pregnancy test and must agree to use 2 highly effective contraceptive methods (hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) during the study and for 3 months after completion of protocol treatment. Females of non-childbearing potential are those who are postmenopausal for greater than 1 year or whom have had a bilateral tubal ligation or hysterectomy.
  8. Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 3 months after completion of protocol treatment.
  9. Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

Exclusion Criteria:

  1. Lymphocyte predominant Hodgkin lymphoma histology.
  2. More than one prior chemotherapy regimen.
  3. Prior autologous or allogeneic stem cell transplant.
  4. Presence of CNS involvement with Hodgkin lymphoma.
  5. Known HIV infection or AIDS.
  6. Active Hepatitis B or C infection or history of cirrhosis.
  7. Grade 2 or greater peripheral neuropathy within 14 days of enrollment.
  8. Hypersensitivity to boron or mannitol.
  9. Prior bortezomib therapy.
  10. Another primary malignancy (other than squamous cell and basal cell carcinoma of the skin, in situ carcinoma of the cervix, or squamous intraepithelial lesion on PAP smear, or treated prostate cancer with a stable PSA) for which the patient has not been disease-free for at least 3 years.
  11. Patients with congestive heart failure, Class III or IV, by New York Heart Association (NYHA) criteria.
  12. Patients with a myocardial infarction 6 months prior to enrollment, uncontrolled angina, severe uncontrolled ventricular arrythmias , or ECG evidence of acute ischemia or active conduction system abnormalities.
  13. Patient with other medical or psychiatric illness that is likely to interfere with participation in this clinical study.
  14. Female subject that is pregnant or breast-feeding.
  15. Patient that has received other investigational drugs within 14 days of enrollment.
  16. Patients using concurrent therapy with corticosteroids at greater than or equal to 20 mg/day of prednisone equivalent.
  17. Patients with active systemic bacterial, viral, or fungal infections that have required IV antimicrobials within 4 weeks prior to protocol treatment.
  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: NCT00967369

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Study Chair: Michelle A. Fanale, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00967369     History of Changes
Other Study ID Numbers: 2008-0604, NCI-2009-01516
Study First Received: August 25, 2009
Last Updated: February 14, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Lymphoma
Classical Hodgkin Lymphoma
Cancer
Bortezomib
Velcade
Chemotherapy
ICE
Ifosfamide
Ifex
Mesna
Mesnex
Carboplatin
Paraplatin
Etoposide
VePesid
BICE
Pegfilgrastim
Neulasta

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Mesna
Etoposide
Etoposide phosphate
Isophosphamide mustard
Bortezomib
Ifosfamide
Carboplatin
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Protease Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 29, 2014