A Phase 1b Study of GDC-0449 following Autologous Transplantation in Patients with High Risk First Remission or Relapsed Multiple Myeloma
â?¢This research is being done to determine if giving a medication that interferes with the Hedgehog pathway after an autologous stem cell transplantation can reduce the risk of your Multiple Myeloma returning. Animal studies have found that blocking the Hedgehog pathway can slow or prevent growth of several different types of human cancer cells grown in animals. In particular, we have found that blocking Hedgehog can slow the growth or kill myeloma cancer stem cells. â?¢GDC-0449, the investigational agent in the form of a pill, has been shown to prevent or slow the growth of several different types of human cancer cells grown in animals. We want to see if it works in humans with multiple myeloma to reduce the chance that the myeloma will come back after a stem cell transplant and to see if it will kill myeloma cancer stem cells in humans.
â?¢Patients must have confirmed multiple myeloma meeting criteria with symptomatic disease requiring treatment. Patients considered to have high risk disease in first remission or Patients with relapsed myeloma responding to salvage therapy based on the International Uniform Response Criteria. â?¢Patients must be planning to proceed to single autologous transplantation according to institutional standards and must receive this transplantation prior to implementation of GDC-0449. â?¢Concomitant bisphosphonate use is allowed as clinically indicated. â?¢Age greater than 18 years â?¢Life expectancy of greater than 6 months. â?¢ECOG performance status less than 2 (Karnofsky greater than 60%; Patients must have adequate liver, kidney and marrow function. â?¢Women of child-bearing potential and men must use two forms of contraception (i.e., barrier contraception and one other method of contraception) at least 4 weeks prior to study entry,for the duration of study participation, and for at least 12 months post-treatment. â?¢Pregnancy Testing. Women of childbearing potential are required to have a negative serum pregnancy test within 24 hours prior to the first dose of GDC-0449 (serum or urine). HIV-positive patients without a prior AIDS-defining illness and a CD4 count greater than 400/millimeter3 and either do not require anti-HIV therapy or are taking anti-HIV therapy that would not interfere with GDC-0449 (e.g. not taking zidovudine, protease inhibitors or non-nucleoside reverse transcriptase inhibitors) are eligible. â?¢Ability to understand and the willingness to sign a written informed consent document. â?¢They are therapeutic on a stable warfarin dose, monitored weekly, with INR target range no greater than 3. Other anticoagulants, including low molecular weight heparin such as Lovenox) and Arixtra)are permitted. â?¢They have no active bleeding or pathological condition that carries high risk of bleeding.
Several tests and procedures are done called â??Screeningâ??. If eligible for this study and agreeable to participation, you will receive an autologous stem cell transplant as part of the standard treatment for your myeloma .Once you and your blood counts recover from the stem cell transplant, your myeloma will be checked again by physical assessment , bone marrow exam and laboratory testing. This period will be approximately between Day 60 and Day 120 after the transplant, If you meet criteria, you will enter the Study Drug Administration period. The study drug (GDC-0449) will be provided in 150-mg capsules. You will take one capsule daily by mouth starting on Day 1 and take for 11 Cycles which is about 365 days. Each cycle is 28 days, and .you will have a study visit every 2 weeks for first 2 cycles, and then once a month for the remaining 9 cycles. At these visits, clinical and research labs, medical history and physical assessments will be done. Bone marrow exams will be several times during the year on study drug. You will be followed up by telephone or be seen in the clinic, for up to four weeks after stop of study drug.
05/22/2013 04:02 AM