Phase I/II Study of Plerixafor and Clofarabine in Previously Untreated Older (>/=60 Years) Adult Patients With Acute Myelogenous Leukemia (AML) With Two or More Unfavorable Prognostic Factors for Whom Standard Induction Chemotherapy is Unlikely to be of Benefit
The Study Drugs:
Plerixafor is designed to block a protein on cancer cells from attaching to cells in the
bone marrow. This may allow cells in the bone marrow to be more effectively treated by
chemotherapy.
Clofarabine is designed to interfere with the growth and development of cancer cells.
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a study
group based on when you joined this study. Up to 3 groups of up to 6 participants will be
enrolled in the Part 1 portion of the study, and up to 48 participants will be enrolled in
Part 2.
If you are enrolled in Part 1, the dose of plerixafor you receive will depend on when you
joined this study. The first group of participants will receive the lowest dose level of
plerixafor. Each new group will receive a higher dose of plerixafor than the group before
it, if no intolerable side effects were seen.
If you are enrolled in Part 2, you will receive plerixafor at the highest dose that was
tolerated in Part 1.
All participants will receive the same doses of clofarabine.
Study Drug Administration:
Cycles in this study are 28 days long, or possibly longer depending on your blood counts,
any side effects, and the status of the disease.
On Days 1-5 of each cycle, you will receive plerixafor through a needle under the skin of
your abdomen.
On Days 1-5 of each cycle, you will receive clofarabine by vein over about 1 hour. The dose
will begin about 4 to 6 hours after the plerixafor injection. You will be watched for side
effects while you receive clofarabine.
If the doctor thinks it is in your best interest, the dose level of plerixafor may be
lowered.
Cycle 1 is called Induction. If the disease goes into remission (responds well) after the
Induction cycle, you will start the Consolidation part of the study. In the Consolidation
cycles, the schedule of administration of the drugs will be the same as in the Induction
cycle, but the doses of clofarabine will be lower. If the disease does not go into remission
after the Induction cycle, you will have a Reinduction cycle before you can begin the
Consolidation part of the study. The goal of the Induction cycle and possible Reinduction
cycle is to affect the bone marrow a certain way that may help control the disease. The
goal of Consolidation is also to help control the disease.
Study Visits:
Induction (Cycle 1) On Day 1 of Induction, blood (about ½ tablespoon each time) will be
drawn for routine tests before the plerixafor injection and 3 times during the 8 hours after
the injection.
On Days 2-5 of Induction, blood (about ½ tablespoon each time) will be drawn for routine
tests before the plerixafor injection and again at 8 hours after the injection.
Starting in Week 2 of Induction, blood (about 2 tablespoons) will be drawn at least 2 times
a week for routine tests.
You will have a bone marrow aspiration and/or biopsy to check the status of the disease on
Day 21 of Induction and every 2 weeks after that, until the Induction cycle is over.
Reinduction:
If you have a Reinduction cycle, blood (about 2 tablespoons) will be drawn at least 2 times
a week during Reinduction for routine tests. You will have a bone marrow aspiration and/or
biopsy to check the status of the disease on Day 21 of Reinduction and every 2 weeks after
that, until the Reinduction cycle is over.
Consolidation:
Blood (about 2 tablespoons) will be drawn 1 time a day for routine tests on Days 1-5 of
Consolidation.
Starting in Week 2 of each Consolidation cycle, blood (about 2 tablespoons) will be drawn
for routine tests every week for the rest of each Consolidation cycle.
You will have a bone marrow aspiration and/or biopsy to check the status of the disease
anytime during Consolidation that the doctor decides it is needed.
Induction, Reinduction, and Consolidation:
The blood tests and/or bone marrow aspirations/biopsies may be performed more often than
listed if the doctor thinks it is needed. Also, you will have an ECG anytime during the
study if the doctor thinks it is needed.
Length of Study:
You may continue taking the study drugs for up to 5 Consolidation cycles, if the doctor
thinks it is in your best interest. You will no longer be able to take the study drugs if
the disease gets worse or intolerable side effects occur.
Your participation on the study will be over once you have completed the follow-up visits.
Follow-Up Visits:
At 1 and 3 months after you stop taking the study drugs:
- Blood (about 2 tablespoon) will be drawn for routine tests.
- If the doctor decides it is needed, you will have a bone marrow aspiration to check the
status of the disease.
If the disease responds (if it goes into complete or partial remission), you will have
follow-up visits every 3 months for up to 2 years after you stop taking the study drugs.
The follow-up visits will stop if the disease gets worse, or if you start a new cancer
therapy and the disease has not gotten worse. The following tests and procedures will be
performed at the follow-up visits:
- Blood (about 2 tablespoon) will be drawn for routine tests.
- If the doctor decides it is needed, you will have a bone marrow aspiration to check the
status of the disease.
This is an investigational study. Clofarabine is FDA approved and commercially available to
treat acute lymphoblastic leukemia (ALL) in children after the disease has gotten worse a
second time. Plerixafor is FDA approved to be given with G-CSF and is commercially
available for use in moving stem cells into the bloodstream before a stem cell transplant to
treat non-Hodgkin's lymphoma or multiple myeloma. The combination of clofarabine and
plerixafor is investigational.
Up to 66 patients will take part in this study. All will be enrolled at M. D. Anderson.
Interventional
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of Participants in Phase I with First Cycle Dose Limiting Toxicities (DLT) Observed
Dose limiting toxicity (DLT) consists of participants who developed DLT during maximum tolerated dose (MTD) estimation period or who completed the MTD estimation period without DLTs. DLTs observed during dose escalation used to develop MTD.
First cycle of treatment, i.e. first 4 weeks on study
Yes
Jan A. Burger, MD
Study Chair
UT MD Anderson Cancer Center
United States: Food and Drug Administration
2009-0536
NCT01160354
August 2010
Name | Location |
---|---|
UT MD Anderson Cancer Center | Houston, Texas 77030 |