Clinical Trial: Phase II Trial of LMB-2, Fludarabine and Cyclophosphamide for Adult T-Cell Leukemia

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional




Official Title: Phase II Trial of LMB-2, Fludarabine and Cyclophosphamide for Adult T-Cell Leukemia

Brief Summary:

BACKGROUND:

  • CD25 (p55, Tac or IL2R alpha) is strongly expressed in virtually 100% of patients with adult T-cell leukemia/lymphoma (ATL), a highly aggressive HTLV-1 related malignancy responding poorly to chemotherapy.
  • In ATL, the humanized anti-CD25 monoclonal antibody (Mab) daclizumab produced 13-14% responses, and the anti-CD52 Mab Alemtuzumab (Campath-1H) produced response lasting greater than 2 months in 30% of 23 patients.
  • LMB-2 is an anti-CD25 recombinant immunotoxin containing variable domains of murine MAb anti-Tac and truncated Pseudomonas exotoxin.
  • In a phase I trial at NCI, the MTD of LMB-2 was 40 microg/Kg IV given every other day for 3 doses (QOD times 3). LMB-2 induced greater than 90% tumor reduction rapidly in all 3 ATL patients on protocol, but achieved only 1 partial response due to rapid tumor progression and/or immunogenicity.
  • In preclinical models, response from recombinant immunotoxins is limited by high concentrations of soluble receptor in the blood and especially in the interstitial space of the tumor. Synergism was observed with chemotherapy and immunotoxins, possibly due to reduction of soluble receptor in tumor interstitium.

OBJECTIVES:

-To determine, in nonrandomized fashion, if after verifying its safety, fludarabine and cyclophosphamide (FC) prior to LMB2 for ATL can result in low immunogenicity and a rate of major response lasting greater than 2 months, which may be an improvement over that demonstrated previously from CAMPATH.

Secondary objectives: