Tipifarnib in Treating Patients With Relapsed or Refractory Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00082888
First received: May 14, 2004
Last updated: May 9, 2014
Last verified: December 2013
  Purpose

This phase II trial studies how well tipifarnib works in treating patients with relapsed or refractory non-Hodgkin's lymphoma. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Tipifarnib may be an effective treatment for non-Hodgkin's lymphoma.


Condition Intervention Phase
Anaplastic Large Cell Lymphoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Nodal Marginal Zone B-cell Lymphoma
Peripheral T-cell Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Small Lymphocytic Lymphoma
Splenic Marginal Zone Lymphoma
Drug: tipifarnib
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Evaluation of FTI (R115777) in Treatment of Relapsed and Refractory Lymphoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Proportion of Confirmed Response (Complete Response, Unconfirmed Complete Response, or Partial Response) During the First 6 Courses of Treatment [ Time Frame: During the first 6 cycles of treatment ] [ Designated as safety issue: No ]
    Confirmed response is at least a 50% decrease in the sum of the products of the greatest diameters (SPD) of the six largest dominant nodes or nodal masses and no increase in the size of other nodes, liver, or spleen and splenic and hepatic nodules must regress by at least 50% in the SPD and no new sites of disease.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Overall survival time was defined as the time from registration to the date of death or last follow-up.

  • Time to Progression [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
    Time to progression was defined as the number of months from registration to the date of disease progression with patients being progression-free being censored on the date of their last evaluation.

  • Duration of Response [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
    Duration of response is defined for all evaluable patients that have achieved an objective response as the date at which the patient's objective status is first noted to be either a complete response or partial response to the date progression is documented.

  • Toxicity [ Time Frame: 3/26/2004 - 2/1/2011 ] [ Designated as safety issue: Yes ]
    Number of patients that experienced a grade 3 or 4 toxicity (adverse events considered at least possibly related to Tipifarnib) as measured by NCI (National Cancer Institute) CTCAE (Common Terminology Criteria for Adverse Events) v3.0


Enrollment: 93
Study Start Date: March 2004
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (tipifarnib)
Patients receive tipifarnib PO BID on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: tipifarnib
Given PO
Other Names:
  • R115777
  • Zarnestra
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess tumor response to R115777 (tipifarnib) in patients with relapsed aggressive non-Hodgkin's lymphoma. (Permanently closed to accrual 6/28/06) II. To assess tumor response to R115777 in patients with relapsed indolent non-Hodgkin's lymphoma. (Permanently closed to accrual 9/26/07) III. To assess tumor response to R115777 in patients with uncommon non-Hodgkin's lymphomas.

IV. To evaluate toxicity associated with this regimen in patients with relapsed non-Hodgkin's lymphoma.

SECONDARY OBJECTIVES:

I. To evaluate known and unknown molecular markers that may predict for response to R115777 in lymphoma tissue.

OUTLINE:

Patients receive tipifarnib orally (PO) twice daily (BID) on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 2 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Biopsy-proven relapsed or refractory lymphomas; previous biopsies =< 6 months prior to treatment on this protocol will be acceptable as long as there has not been intervening therapy; if the patient has received therapy for non-Hodgkin's disease (NHL) between the time of the last biopsy and this protocol, then a re-biopsy is necessary
  • STUDY 1: Aggressive lymphomas (permanently closed to accrual 6/28/06):

    • Transformed lymphomas
    • Diffuse large B cell lymphoma
    • Mantle cell lymphoma
    • Follicular lymphoma grade III STUDY 2: Indolent lymphomas (permanently closed to accrual 9/26/07)
    • Small lymphocytic lymphoma/chronic lymphocytic leukemia
    • Follicular lymphoma, grades 1, 2
    • Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type
    • Nodal marginal zone B-cell lymphoma
    • Splenic marginal zone B-cell lymphoma

STUDY 3: Uncommon lymphomas:

  • Peripheral T cell lymphoma, unspecified
  • Anaplastic large cell lymphoma (T and null cell type)
  • Lymphoplasmacytic lymphoma
  • Mycosis fungoides/ Sezary syndrome
  • Relapsed Hodgkin's disease (patients must be previously treated and either have had a transplant or not be eligible for a transplant)

    • Previously treated (no limitations on the number of prior therapies); patients with aggressive lymphoma (Study 1 - permanently closed to accrual 6/28/06) should have received or be ineligible for potentially curable therapy including stem cell transplant
    • MEASURABLE DISEASE: Must have at least one lesion that has a single diameter of >= 2 cm or tumor cells in the blood >= 5 x10^9/L
    • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
    • Absolute neutrophil count >=1000/mm^3
    • Platelet count >= 75,000
    • Hemoglobin >= 9 g/dL
    • Total bilirubin =< 2 x upper limit of normal (ULN) (if > 2 x ULN direct bilirubin is required and should be =< 1.5 x ULN)
    • Aspartate aminotransferase (AST) =< 3 x ULN (=< 5 x ULN if liver involvement is present)
    • Serum creatinine =< 2 x ULN
    • Expected survival >= 3 months
    • Capable of understanding the investigational nature, potential risks and benefits of the study and able to provide valid informed consent
    • Capable of swallowing intact study medication tablets
    • Capable of following directions regarding taking study medication, or has a daily caregiver who will be responsible for administering study medication

Exclusion Criteria:

  • Any of the following as this regimen may be harmful to a developing fetus or nursing child:

    • Pregnant women
    • Breastfeeding women
    • Men or women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.)
    • NOTE: The effects of R115777 on the developing human fetus at the recommended therapeutic dose are unknown
  • Life-threatening illness (unrelated to tumor)
  • Ongoing radiation therapy or radiation therapy =< 3 weeks prior to study registration unless the acute side effects associated with such therapy are resolved
  • Therapy with myelosuppressive chemotherapy, cytotoxic chemotherapy, or biologic therapy =< 3 weeks (6 weeks for nitrosourea or mitomycin C) or corticosteroids =< 2 weeks, prior to starting R11577; patients may be on corticosteroids or tapering off them up until the day they start R11577 as long as it is clear that they are not having a tumor response to the steroids or that the steroids would confuse the interpretation of response to R11577; patients may be receiving stable (not increased within the last month) chronic doses of corticosteroids with a maximum dose of 20 mg of prednisone per day if they are being given for disorders other than lymphoma such as rheumatoid arthritis, polymyalgia rheumatica, adrenal insufficiency, or intractable symptoms of lymphoma
  • Peripheral neuropathy >= grade 3
  • Serious non-malignant disease such as active infection or other condition which in the opinion of the investigator would compromise other protocol objectives
  • Presence of central nervous system (CNS) lymphoma
  • Other active malignancies
  • Once a patient begins FTI (tipifarnib) treatment, the addition of other cancer treatment will confound the assessment of efficacy and therefore is not allowed; this restriction precludes the addition of cytotoxic, immunologic agents, radiotherapy, or an increase in corticosteroid dose while the patient is in the treatment phase of this protocol
  • Known to be human immunodeficiency virus (HIV) positive; HIV testing is not required but should be done if clinically indicated; HIV patients are excluded because of concerns regarding excess risk of complications of immunosuppressive therapy regimens
  • Known allergy to imidazole drugs such as clotrimazole, ketoconazole, miconazole, econazole, fenticonazole, sulconazole, tioconazole, or terconazole
  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: NCT00082888

Locations
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Investigators
Principal Investigator: Thomas Witzig Mayo Clinic
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00082888     History of Changes
Other Study ID Numbers: NCI-2012-02849, NCI-2012-02849, 6246, LS038B, 6246, P50CA097274
Study First Received: May 14, 2004
Results First Received: November 2, 2011
Last Updated: May 9, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Hodgkin Disease
Lymphoma, Mantle-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Large B-Cell, Diffuse
Lymphoma, B-Cell
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, T-Cell
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma, Large-Cell, Anaplastic
Lymphoma, T-Cell, Peripheral
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Leukemia, Lymphoid
Leukemia
Tipifarnib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014