Arsenic Trioxide in Treating Patients With Relapsed or Refractory Lymphoma or Leukemia

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Terminated

CT.gov ID

NCT00005786

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

Brief Summary

Phase II trial to study the effectiveness of arsenic trioxide in treating patients who have relapsed or refractory lymphoma or leukemia. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die

Condition or Disease	Intervention/Treatment	Phase
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Nodal Marginal Zone B-cell Lymphoma Prolymphocytic Leukemia Recurrent Adult Diffuse Small Cleaved Cell Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Small Lymphocytic Lymphoma Refractory Chronic Lymphocytic Leukemia Splenic Marginal Zone Lymphoma Waldenström Macroglobulinemia	Drug: arsenic trioxide Other: laboratory biomarker analysis	N/A

Detailed Description

PRIMARY OBJECTIVES:

To evaluate the safety and toxicity profile of arsenic trioxide in patients with relapsed or refractory low-grade lymphomas.
To determine the incidence of complete and partial responses to arsenic trioxide in patients with previously treated low-grade lymphomas.
To evaluate basic science correlates of arsenic trioxide activity in order to improve our understanding of the mechanism of action for arsenic trioxide in patients with low-grade lymphomas.

OUTLINE: This is a nonrandomized, open-label study.

Patients receive arsenic trioxide IV over 1-4 hours on days 1-5. Treatment repeats every 21 days for a maximum of 6 courses in the absence of unacceptable toxicity or disease progression. Patients with responding or stable disease may receive 6 additional courses.

Patients are followed every 3 months for up to 2 years.

Study Design

Study Type:

Interventional

Actual Enrollment :

25 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Pilot Study of Arsenic Trioxide in the Treatment of Relapsed and Refractory Indolent Lymphomas

Study Start Date :

Jan 1, 2001

Actual Primary Completion Date :

Nov 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (arsenic trioxide) Patients receive arsenic trioxide IV over 1-4 hours on days 1-5. Treatment repeats every 21 days for a maximum of 6 courses in the absence of unacceptable toxicity or disease progression. Patients with responding or stable disease may receive 6 additional courses.	Drug: arsenic trioxide Given IV Other Names: Arsenic (III) Oxide Arsenic Sesquioxide Arsenous Acid Anhydride AS2O3 Trisenox Other: laboratory biomarker analysis Correlative studies

Arm

Intervention/Treatment

Experimental: Treatment (arsenic trioxide)

Drug: arsenic trioxide

Given IV

Other Names:

Arsenic (III) Oxide

Arsenic Sesquioxide

Arsenous Acid Anhydride

AS2O3

Trisenox

Other: laboratory biomarker analysis

Correlative studies

Outcome Measures

Primary Outcome Measures

Toxicity as assessed by Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria version 2.0 [Up to 2 years after completion of study treatment]
Incidence of complete and partial response [Up to 2 years]

Secondary Outcome Measures

Potential surrogate of arsenic trioxide clinical activity [From baseline to up to 2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients must have a diagnosis of relapsed or refractory low-grade lymphoma
Patients must have disease that has relapsed from or is refractory to standard cytotoxic therapy; patients must have received at least one standard cytotoxic drug regimen; there is no limit on the number of prior therapies, including high dose chemotherapy regimens, provided the patient has recovered from prior toxicities; relapsed disease is defined as the development of lymphadenopathy, splenomegaly, malignant lymphocytosis greater than 5,000, or infiltration of the bone marrow with malignant lymphocytes in a patient who had previously achieved a response of at least six months in duration; refractory disease is defined as never achieving a PR or a CR or PR that is less than six months in duration; prior total body irradiation is not allowed; radiation to individual site is permitted, and is not included as a regimen
Serum creatinine =< 2.0 mg/dl
Total bilirubin =< 2.0 mg/dl
Serum SGOT, SGPT =< 2.5 times the upper limit of institutional normal
Patients who are female and have childbearing potential must have a negative pregnancy test; all patients who are engaging in sexual intercourse that may result in a pregnancy must use appropriate contraception while receiving treatment on this protocol
Patients must have sufficient mental capacity to understand the explanation of the study and to give his or her informed signed consent
Patients must display Karnofsky performance status of 60% or greater
Patients should have a life expectancy of > 12 weeks so as to permit adequate follow-up of toxicity
Patients must have recovered from the toxicity of recent therapy prior to enrollment in this study
Absolute neutrophil count > 1500/uL, unless cytopenias are the result of bone marrow infiltration by lymphoma; permission of the protocol PI is required in this situation
Platelet count > 75,000/uL, unless cytopenias are the result of bone marrow infiltration by lymphoma; permission of the protocol PI is required in this situation; patients with thrombocytopenia secondary to active ITP or anemia secondary to an active autoimmune hemolytic anemia at the time of evaluation are excluded

Exclusion Criteria:

Pregnant or lactating women; arsenic compounds could be transferred to the fetus or child with resultant harm
Concurrent treatment with cytotoxic chemotherapy, radiation or investigational agents; this exclusion does not include concurrent glucocorticoids fro brief durations; patients must have recovered from the toxicity of prior therapy prior to enrollment in this study
Active serious infections not controlled by antibiotics
Inability to comply with the treatment protocol or follow-up testing
Patients with HIV infection; there are currently insufficient data to support the safety of administering arsenic compounds in combination with anti-retroviral drugs
Patients with active viral or autoimmune hepatitis
Patients with history of cardiac arrhythmia, heart block, or myocardial infarction within the past 6 months
Patients with known CNS disease
Patients requiring amphotericin B therapy
Patients with significant peripheral neuropathy (>= grade 3), regardless of cause