Thalidomide in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
Thalidomide in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
Phase II trial to study the effectiveness of thalidomide in treating patients who have
 relapsed or refractory low-grade non-Hodgkin's lymphoma. Thalidomide may stop the growth of
 non-Hodgkin's lymphoma by stopping blood flow to the tumor
PRIMARY OBJECTIVES:

 I. To estimate the response rate and time-to-progression (TTP) in previously treated patients
 with low grade non-Hodgkin's lymphoma treated with thalidomide.

 II. To evaluate the effect of thalidomide on microvascular density in the bone marrow of
 patients with low grade cell non-Hodgkin's lymphoma.

 III. To evaluate the effects of thalidomide on bFGF levels in serum and urine.

 OUTLINE:

 Patients receive oral thalidomide once daily. Treatment continues in the absence of disease
 progression or unacceptable toxicity.

 Patients are followed every 6 months for 2 years and then annually for 3 years.

 PROJECTED ACCRUAL: A total of 21-45 patients will be accrued for this study.
Inclusion Criteria:

 -  Histologically documented non-Hodgkin's lymphoma; core biopsies are acceptable if they
 contain adequate tissue for primary diagnosis and immunophenotyping; bone marrow
 biopsies as the sole means of diagnosis are not acceptable for follicular lymphomas;
 patients with NHL must have one of the following World Health Organization (WHO)
 histologic subtypes:

 -  Follicular, grade 1

 -  Follicular, grade 2

 -  Follicular, grade 3

 -  B-cell small lymphocytic lymphoma

 -  Note: Patients diagnosed more than one year prior to entry on protocol must have
 a repeat lymph node biopsy; in the event of rapid tumor growth, rising LDH, or
 the onset of B symptoms in a period of time less than one year a rebiopsy is also
 required; patients are ineligible for this study if a separate lymph node biopsy
 shows a lymphoma with a higher grade; failure to submit pathology slides within
 60 days of patient registration will result in patient being declared ineligible

 -  No known lymphomatous involvement of the CNS including either parenchymal or
 leptomeningeal involvement (lumbar puncture prior to study is not required in the
 absence of neurologic symptoms) or any seizure disorders or prior brain injury which
 could precipitate seizures

 -  Measurable disease must be present either on physical examination or imaging studies;
 evaluable disease alone is not acceptable; any tumor mass reproducibly measurable in
 two perpendicular diameters and > 1x1 cm by physical examination, X-ray, computerized
 tomography (CT), or magnetic resonance imaging (MRI) is acceptable; whenever CT is
 specified, it should be understood that MRI may be substituted as long as the
 measurements for tumor response are made on two successive studies employing the same
 procedure; the following lesions are not considered measurable:

 -  Barium studies

 -  Ascites or pleural effusion

 -  Bony disease (lesions if present should be noted)

 -  Bone marrow

 -  Patients must have received no more than 3 prior chemotherapy regimens and no more
 than 2 prior antibody treatments; patients who have failed to respond to 3 regimens of
 prior chemotherapy (i.e., refractory to 3 regimens) are not eligible

 -  NCI CTC performance status of 0 or 1

 -  Pregnant and nursing women are not eligible for treatment on this protocol; women of
 childbearing potential must agree to abstain from all intercourse or use two methods
 of birth control for 28 days prior to treatment and while under treatment with
 thalidomide and for four weeks after completing therapy; one of the methods of birth
 control must be highly active (IUD, hormonal, tubal ligation or partner's vasectomy)
 and used concomitantly with one additional method (e.g., latex condom, diaphragm or
 cervical cap); these precautions are required even in patients with a history of
 infertility unless due to hysterectomy or because the patient has been post menopausal
 or has had no menses for at least 24 consecutive months; in addition, women of
 childbearing potential must have serum B-HCG performed prior to treatment, weekly for
 the first 4 weeks of treatment and then every four weeks if menses are regular and
 every two weeks if menses are irregular; men must agree to abstain from unprotected
 sexual intercourse; male patients should request that female partners use a second
 method of birth control in addition to the male barrier method

 -  No known HIV disease; patients with a history of intravenous drug abuse or any other
 behavior associated with an increased risk of HIV infection should be tested for
 exposure to the HIV virus; because peripheral neuropathies are a common toxicity of
 antiviral therapy and of viral infection in HIV patients, as well as a common
 significant toxicity with thalidomide, patients who test positive or who are known to
 be infected are not eligible; an HIV test is not required for entry on protocol, but
 is required if the patient is perceived to be at risk

 -  No peripheral neuropathy > grade 1

 -  Patients requiring the use of bisphosphonates (e.g., zoledronic acid) are not
 eligible; patients who receive thalidomide in combination with zoledronic acid are
 potentially at increased risk of renal dysfunction; patients enrolled on study prior
 to 15 September 2003 who are receiving bisphosphonates may continue to receive
 thalidomide and bisphosphonate but must have serum creatinine monitored prior to each
 bisphonate infusion; in addition, please inform these patients of the potential for
 renal dysfunction with this combination; this discussion must be documented in the
 patient record

 -  ANC ≥ 750/μL

 -  βHCG negative (in female patients unless S/P hysterectomy or menopausal or no menses
 for 24 consecutive months); assay must have a sensitivity of at least 50 mIU/mL

 -  Creatinine ≤ 2 x normal

 -  Bilirubin ≤ within institutional normal limits

 -  AST and ALT ≤ 2.5 x upper limit of normal