Hi Shane,
SKI-606 is known as a SARC inhibitor, it inhibits SRC kinases and it
also inhibits BCR-ABL. I do not think SKI is explicitly recruiting
patients for T315I but it is not listed in the exclusion criteria so we
may have to wait for Phase I trial results to see if it actually works
for T315I patients as well, like we had to wait for Dasatinib and
AMN107 Phase I trial results to find out that these drugs,
unfortunately, does not work for T315I in human trials. I know a
patient on SKI and I know it is opening worldwide trials. The SKI-606
publication addressing T315I is a preclinical study and there are two
analogs of SKI which are much more potent against T315I than SKI,
itself. Whether these will be actually developed or not is anyone's
guess. I just think it is encouraging that so many drug companies have
taken up the issue of Gleevec resistance.
It is also important to remember that T315I patients can also have
other BCR-ABL point mutations like I know a patient who had F359V and
T315I so drugs are needed targeting all mutations as well as wild-type
BCR-ABL. And again, there can be Gleevec resistance that is primary
and which has nothing to do with mutations and this area needs
addressing as well.
VX-680 is very different from the other inhibitors, it is an Aurora
kinase inhibitor with potent activity against T315I. If I were a
patient harboring only T315I as the predominant path of Gleevec
resistance, I would certainly discuss this drug with my treating
physician.
It is interesting Celtic mentions about VX-680 in tablet form. Being
very ignorant on these issues, I wonder if good responses (I will let
the data speak and I have not seen that yet) from a drug as an infusion
will have equal effect as oral pills and whether separate clinical
trials are to be designed to recognize that. Meaning, once you have
good responses in human trials of a drug given as an infusion, would
FDA approve that drug in pill form based on infusion results without
carrying on a separate trial where patients take the pill. One reason
I bring this point up is that patients obviously want to take the pill
as out of state patients can only stay at a trial center for a short
time due to financial burdens and with an infusion type trial, this
poses a problem to patients coming from places outside the trial
center.
Going by Homoharringtonine, I believe it was given as an infusion first
but separate trials had to be conducted with it in subcutaneous
injection form. So, I think this is an interesting question.
Well, this has been an interesting discussion, all I can say is that
I am very hopeful for Gleevec resistant patients and that they will be
helped by one of these drugs. Also, I am encouraged that the drugs are
coming from different drug companies and competition can bring the
price down of drugs which is an added and important benefit for CML
patients. I have given the SKI trial criteria below and I do hope that
the clinical trials website updates the VX-680 criteria as the last
time I looked, it was still recruiting for blast phase patients.
Clinical trial info reaches worldwide so it is good to keep updating
them.
Best Wishes,
Anjana
caregiver to Roy
400mg Gleevec
Study Evaluating SKI-606 in Philadelphia Chromosome Positive Leukemias
This study is currently recruiting patients.
Verified by Wyeth January 2006
Sponsored by: Wyeth
Information provided by: Wyeth
ClinicalTrials.gov Identifier: NCT00261846
Purpose
This is an open-labeled, continuous daily dosing, two-part safety and
efficacy study of SKI-606 in Philadelphia chromosome positive leukemias
(Ph+). Part 1 is a dose-escalation study in chronic phase Chronic
Myelogenous Leukemia (CML) subjects to establish the Maximum tolerated
dose (MTD) in this subject population. Part 2 will begin after the
completion of Part 1 and after a clear MTD has been established for the
compound in chronic phase subjects. Part 2 will include patients in all
phases of Ph+ CML and Ph+ Acute Lymphocytic Leukemia (ALL). The
protocol will test the hypotheses that oral daily dosing of SKI-606 at
the MTD, or a lower dose will attain; (1) Major Cytogenetic Response
(McyR) in chronic phase patients and (2) a return to chronic phase in
advanced leukemia patients. Each phase of the disease will be evaluated
as a separate cohort.
Condition Intervention Phase
Leukemia, Myeloid, Chronic
Drug: SKI-606
Phase I
Phase II
MedlinePlus related topics: Leukemia, Adult Acute; Leukemia, Adult
Chronic; Leukemia, Childhood
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled,
Single Group Assignment, Safety/Efficacy Study
Official Title: A Phase 1/2 Study of SKI-606 in Philadelphia Chromosome
Positive Leukemias
Further study details as provided by Wyeth:
Expected Total Enrollment: 100
Study start: January 2005
Eligibility
Ages Eligible for Study: 18 Years and above, Genders Eligible for
Study: Both
Criteria
Inclusion Criteria:
Ph+ CML or Ph+ ALL who are primarily refractory to full-dose imatinib
(600 mg), have disease progression/relapse while on full-dose imatinib,
or are intolerant of any dose of imatinib.
At least 4 months post stem cell transplantation
Able to take daily oral capsules reliably
Exclusion Criteria:
Subjects with Philadelphia chromosome, and bcr-abl negative CML
Overt leptomeningeal leukemia
Subjects without evidence of leukemia in bone marrow (extramedullary
disease only)
Location and Contact Information
Please refer to this study by ClinicalTrials.gov identifier
NCT00261846
Trial Manager [EMAIL PROTECTED]
New York
Rochester, New York, 14642, United States; Not yet recruiting
See Central Contact
Valhalla, New York, 10595, United States; Not yet recruiting
See Central Contact
Texas
Houston, Texas, 77030, United States; Recruiting
See Central Contact
Study chairs or principal investigators
Medical Monitor, Study Director, Wyeth Research
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