High Dose Interleukin-2 Followed by Intermittent Low Dose Temozolomide in Patients With Melanoma
Condition: Malignant Melanoma
MeSH terms: Melanoma
Intervention: Interleukin-2; Temozolomide
Intervention description: Participants will receive IL-2 up to a maximum of 14 doses at 600,000 IU/kg; Participants receive temozolomide at 75 mg/m2 after completion of the second cycle of high dose IL-2. Participants take the medication at bedtime daily. Four weeks after Cycle 2 of a course, they would take it for 21 days.
Intervention MeSH terms: Temozolomide; Interleukin-2
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Single group, open label study
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic melanoma

Summary:

      The investigators have observed that many patients who had received high dose Interleukin-2
      (IL2) and failed to respond to it but who then go immediately to temozolomide seemed to enjoy
      extremely good responses which seem better quality and longer duration than typically
      observed for temozolomide alone. To date, the investigators have observed 5 sequentially
      treated patients with metastatic melanoma who had failed high dose IL-2 but who then went on
      to receive immediate temozolomide. Two of these patients had complete responses and 3 had
      very strong partial response. In a recent phase II study of extended low dose temozolomide
      alone given in the same manner as the post IL-2 patients noted above, the response rate was
      12.5% and all of these were partial responses only. The responses that the investigators
      observed were at a much higher rate of response as well as much better quality than expected
      for temozolomide. The responses were also better than those observed when temozolomide was
      given first and then followed by high dose IL-2. The investigators concluded that perhaps the
      major benefit the investigators observed was a result of the prior high dose IL-2 therapy
      modulated by the temozolomide and that the sequence of treatment was clearly crucial for this
      response.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pathologically confirmed metastatic malignant melanoma

          -  Age > 18 years

          -  Eastern Cooperative Oncology Group performance status of 0 or 1

          -  Patients considered good candidate for conventional high dose IL-2

          -  No chemotherapy, hormonal therapy, immunotherapy or radiation therapy within 1 month
             of entry

          -  Patients with a history or clinical evidence of brain metastasis must have completed
             radiation therapy or surgical treatment of brain lesions and have no evidence of
             central nervous system progression for at least 8 weeks at the time of enrollment.

          -  Patients may have had prior high dose IL-2 or temozolomide but not together or with
             high dose IL-2 followed by temozolomide

          -  Patients may have had prior high dose interferon as adjuvant treatment for high risk
             melanoma

          -  Serum creatinine < 2 mg/dL

          -  Bilirubin < 2 mg/dL

        Exclusion Criteria:

          -  Inability to provide informed consent

          -  Hypersensitivity to temozolomide or HD IL-2

          -  Active gastrointestinal disorder or cardiac disorders

          -  Ejection fraction < 50% by echocardiogram or corrected diffusing capacity of lung for
             carbon monoxide < 50% on diffusion capacity testing pulmonary function tests

          -  platelets < 100 K, neutrophils < 1000

          -  Serum Creatinine < 2 x the upper limits of normal

          -  Chronic use of steroids other than for simple adrenal replacement