SL-11047 in Treating Patients With Relapsed or Refractory Lymphoma

Progen Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Lymphoma

Treatments: Drug: polyamine analogue PG11047

Study type: Interventional

Funder types: Industry; NIH

Identifiers

NCT00293488

PROGEN-SL002

UCSF-H1956-21906-02

UCSF-SL002

CDR0000463738 (Registry Identifier)

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as SL-11047, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase I trial is studying the side effects and best dose of SL-11047 in treating patients with relapsed or refractory lymphoma.

Full description

OBJECTIVES:

Primary

• Determine the maximum tolerated dose (MTD) of SL-11047 in patients with relapsed or refractory lymphoma.
• Describe and quantify the toxicity of SL-11047 administered to patients with relapsed or refractory lymphoma.

Secondary

• Describe the pharmacokinetics of SL-11047 administered as a 30-minute IV infusion.
• Assess the response rate and duration of response in patients treated with SL-11047.
• Assess the level of SL-11047 within tumor tissues following intravenous administration of the drug.
• Determine the sensitivity of abnormal circulating macrophages to SL-11047.

OUTLINE: This is an open-label, nonrandomized, dose-escalation study.

Patients receive SL-11047 IV over 30 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of SL-11047 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Enrollment: 20 estimated patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically* confirmed Hodgkin's or non-Hodgkin's lymphoma (NHL) of any histology

  • The following NHL types are eligible:

    • Diffuse large B-cell lymphoma
    • Follicular lymphoma
    • Mantle Cell lymphoma
    • Marginal zone lymphoma (including lymphoma of mucosa-associated tissue [MALT])
    • Anaplastic large cell lymphoma
    • Peripheral T-cell lymphoma
    • Cutaneous T-cell lymphoma
    • T/NK cell lymphoma
    • Angioimmunoblastic lymphadenopathy-type T-cell lymphoma
    • Burkitt's lymphoma NOTE: * If histologic confirmation was made at initial diagnosis, confirmation of relapsed or refractory disease can be made by repeat histologic evaluation OR by evidence of regrowth at a site of disease that was previously histologically confirmed

• Relapsed after or refractory to ≥ 2 prior therapeutic regimens OR patient is ineligible to receive potentially curative therapy

• Bidimensionally measurable or evaluable (e.g., bone marrow or infiltrative organ involvement) disease by physical exam or radiographic study

• No suspicion or evidence of lymphomatous meningitis

PATIENT CHARACTERISTICS:

• Life expectancy ≥ 12 weeks

• ECOG performance status 0-4

• Not pregnant

• Negative pregnancy test

• Fertile patients must use medically prescribed contraception

• Absolute neutrophil count ≥ 1,000/mm^3*

• Platelet count ≥ 50,000/mm^3*

• Hemoglobin ≥ 8 g/dL*

• Serum creatinine ≤ 2.0 mg/dL

• Total bilirubin ≤ 2.0 mg/dL**

• Transaminases < 5 times upper limit of normal**

• No other malignancy within the past 5 years other than curatively treated non-metastatic skin cancer or in situ cervical carcinoma

• No history of significant or symptomatic cardiac arrhythmia

• No history of myocardial infarction

• No significant ventricular conduction abnormality by ECG or Holter monitoring, as evidenced by any of the following:

  • Prior myocardial infarction
  • Three or more premature ventricular contractions in a row

• No history of pancreatitis

• No history of recent gastrointestinal bleeding

  • Must have heme-negative stool at enrollment NOTE: *Cytopenias due to direct lymphomatous involvement allowed

NOTE: **Elevated due to direct lymphomatous involvement allowed

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• More than 3 weeks since prior chemotherapy
• Recovered from prior chemotherapy (alopecia or anemia allowed)
• More than 3 weeks since prior investigational drugs
• No prophylactic antiemetics during course 1
• No other concurrent investigational drugs