Phase I-II study of Genasense (Bcl-2 Antisense Oligonucleotide) in Patients With Advanced Chronic Lymphocytic Leukemia

Reviewer: Julie Draznin Maltzman, MD
Last Modified: December 7, 2002

Presenter: Kanti R. Rai
Presenter's Affiliation: Long Island Jewish Medical Center
Type of Session: Poster


    Chronic Lymphocytic Leukemia (CLL) is the most common chronic leukemia in adults. It's course is usually slow and insiduous however treatment options are often limited due to severe anemias and thrombocytopenias. A novel therapy by Genta Inc called Genasense is a oligonucleotide that targets and destroys the message RNA for Bcl-2, the anti-apoptotic protien that drives this leukemia. In a previous Phase I trial, 14 patients with refractory or heavily pretreated stage II-IV CLL were given IV infusions of Genasense. Unexpected tumor activity was noted when used as a single agent with decrease in the size and number of lymph nodes as well as a decrease in the size of the spleen.

Materials and Methods

  • 40 patients were entered in the combined phase I and II trials. 14 in phase I and 26 in phase II.
  • Phase I was to determine the maximum tolorated dose (MTD).
  • The goal of phase II trial was to evaluate single agent activity.
  • Patients were given a daily continuous IV infusion of Genesense for 5-7 days every 3-4 weeks. The doses started at 3mg/kg/d and escalated to 7mg/kg/d in the phase I part of the trial and remained at 3mg/kg/d for the phase II.
  • Response was evaluated by CT scans to evaluate lymph node number and size, as well as by the number of circulating CLL cells.


  • 3-4mg/kg/d was found to be a well tolorated dose with only rare toxicity of greater than grade 3. The most common toxicity was low grade fever. Other adverse events include fatigue, night sweats, and mild dyspnea.
  • A reduction in circulating CLL cells of >25% from baseline was seen in 63% of the patients.
  • A decrease in lymphodenopathy was reported in 35% of the patients.
  • A decrease in hepato-splenomegally was noted in 33% of the patients.

Author's Conclusions

    The authors conclude that this supports the previous study that Bcl-2 antisense has anti-tumor activity in CLL even in the absence of other cytotoxic drugs.

Clinical/Scientific Implications

    This is another of the new biologic therapy agents that are being evaluated in the treatment of CLL. Because patients can live many years with CLL without symptoms it is important to find active agents with little toxicity. This early study of Genasense is encouraging. A question that remains is the potential enhancement of cytotoxic chemotherapy with Genasense. Trials looking at Fludarabine+cyclophosphamide with or without Genasense are currently ongoing.

Oncolink's ASH Coverage made possible by an unrestricted Educational Grant from Ortho Biotech.