17-AAG in Treating Patients With Relapsed or Refractory Anaplastic Large Cell Lymphoma, Mantle Cell Lymphoma, or Hodgkin's Lymphoma

PRIMARY OBJECTIVE:

I. Determine the complete and partial response rates and time to treatment failure in patients with relapsed or refractory anaplastic large cell lymphoma, mantle cell lymphoma, or classical Hodgkin's lymphoma treated with 17-N-allylamino-17-demethoxygeldanamycin (17-AAG).

SECONDARY OBJECTIVES:

I. Determine the safety of this drug in these patients. II. Determine the biologic effect of this drug on selected molecular targets in primary lymphoma cells from these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to disease type (anaplastic large cell lymphoma vs mantle cell lymphoma vs Hodgkin's lymphoma).

Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 1 hour on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing disease regression after completion of 8 courses may receive 2 additional courses of treatment beyond their maximal response.

After completion of study treatment, patients are followed every 3 months until disease progression.

Inclusion criteria

• Negative pregnancy test
• Fertile patients must use effective contraception prior to and during study treatment
• Must have normal organ and marrow function
• Not a candidate for stem cell transplantation
• ECOG 0-2 OR Karnofsky 60-100%
• Bilirubin normal
• Creatinine normal
• Histologically or cytologically confirmed relapsed or refractory mantle cell lymphoma, anaplastic large cell lymphoma (CD30-positive disease), or classical Hodgkin's lymphoma
• Recovered from prior biologic therapy or autologous stem cell transplantation
• Prior antibody therapy within the past 3 months allowed
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• More than 4 weeks since prior radiotherapy (12 weeks for radioimmunotherapy) and recovered
• Recovered from prior investigational drugs
• Recovered from prior surgery
• More than 4 weeks since other prior anticancer therapy
• Concurrent low-molecular weight heparin is allowed
• Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm
• Absolute neutrophil count >= 1,500/mm3
• Received >= 1, but =< 3, prior treatment regimens for lymphoma (salvage therapy followed immediately by stem cell transplantation is considered 1 regimen). Single-agent monoclonal antibody therapy, cytokine therapy, or involved field radiotherapy are not considered prior treatment regimens. All prior treatments and prior antibody therapy within the past 3 months are recorded.
• Platelet count >= 75,000/mm3
• AST and ALT =< 1.5 times upper limit of normal
• Understand and provide signed informed consent.

Exclusion criteria

• No cardiac arrhythmia or uncontrolled dysrhythmia
• No history of myocardial infarction within the past year
• No New York Heart Association class III or IV heart failure
• No other significant cardiac disease
• No paroxysmal nocturnal dyspnea
• No oxygen requirement
• No AIDS
• No history cardiac toxicity after receiving anthracyclines (e.g., doxorubicin hydrochloride, daunorubcin hydrochloride, mitoxantrone, bleomycin, or carmustine)
• No pulmonary lymphoma
• No known CNS lymphoma
• QTc >/= 450 msec for men
• QTc >/= 470 msec for women
• LVEF </= 40% by MUGA
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No symptomatic pulmonary disease requiring medication
• No significant pulmonary disease including chronic obstructive or restrictive pulmonary disease
• No dyspnea on or off exertion
• No history of pulmonary toxicity after receiving anthracyclines (e.g., doxorubicin hydrochloride, daunorubcin hydrochloride, mitoxantrone, bleomycin, or carmustine)
• Not pregnant or nursing
• No other uncontrolled illness
• No other active* malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix
• No prior allogeneic stem cell transplantation
• No history of allergic reaction to eggs
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No prior chest radiation or prior radiation that potentially included the heart in the field (e.g.,mantle).
• No concurrent medications that prolong or may prolong QTc
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational agents
• No other concurrent anticancer therapy
• No prior cardiac symptoms >= grade 2
• No sufficiently compromised pulmonary status (i.e., DLCO =< 80%)
• No history of serious ventricular arrhythmia (e.g., ventricular tachycardia or ventricular fibrillation >= 3 beats in a row)
• No prior pulmonary symptoms >= grade 2
• HIV negative
• No active ischemic heart disease within 12 months.
• No congenital long QT syndrome.
• No left bundle branch block.