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A Phase 2 Study of the Combination of the Bruton's Tyrosine Kinase Inhibitor PCI-32765 and Rituximab in High-Risk Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL) Patients


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Leukemia

Thank you

Trial Information

A Phase 2 Study of the Combination of the Bruton's Tyrosine Kinase Inhibitor PCI-32765 and Rituximab in High-Risk Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL) Patients


Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive rituximab by
vein on Days 1, 8, 15, and 22 of Cycle 1 (+ 3 days) and then on Day 1 (+/- 7 days) of
Cycles 2-6.

Each cycle is 28 days.

You will take PCI-32765 capsules by mouth 1 time each day starting on Day 2 of Cycle 1. You
should take it with 1 cup (8 ounces) of water.

You will also take allopurinol by mouth 1 time each day during the first 1-2 weeks of study
treatment to lower the risk of side effects.

Study Visits:

On Days 7, 14, 21, and 28 of Cycle 1 (+/- 3 days):

- You will have a physical exam, including measurement of your vital signs.

- Blood (about 1 tablespoon) will be drawn for routine tests.

- You will be asked about any drugs you may be taking.

At the end of Cycles 2, 3, 4, 6, 9, and 12 (+/- 1 month):

- You will have a physical exam, including measurement of your vital signs.

- Blood (about 1 tablespoon) will be drawn for routine tests.

- You will be asked about any drugs you may be taking.

At the end of Cycles 3 or 6, and 12 (+/- 1 month), and then every 12 cycles (+/- 1 month)
after that if the doctor thinks it is needed, you will have CT scans of the chest, abdomen
and pelvis to check the status of the disease.

At the end of Cycles 3, 6, and 12 and then every 12 cycles (+/- 1 month) after that, you
will have a bone marrow aspiration to check the status of the disease. If the doctor things
these bone marrow aspirations are no longer needed, you will no longer have to have them.

Every 3 months (+/- 1 month) for Cycles 13-36 and every 6 months (+/- 1 month) after that:

- You will have a physical exam, including measurement of your vital signs.

- Blood (about 1 tablespoon) will be drawn for routine tests.

- You will be asked about any drugs you may be taking.

Length of Treatment:

You may continue taking the study drug combination of rituximab and PCI-32765 for up to 6
cycles, after which PCI-32765 will be continued for up to a total of 12 cycles. It will be
possible to continue with PCI-32765 treatment beyond 12 cycles if the study doctor thinks it
is in your best interest. You will no longer be able to take the study drug if the disease
gets worse, if intolerable side effects occur, or if you are unable to follow study
directions.

This is an investigational study. PCI-32765 is not commercially available or FDA approved.
It is currently being used for research purposes only. Rituximab is FDA approved to treat
CLL and SLL.

Up to 40 patients will take part in this study. All will be enrolled at MD Anderson.


Inclusion Criteria:



1. 1.Patients must have a diagnosis of high-risk CLL/SLL and be previously treated with
up to 3 lines of prior therapy. High-risk CLL and high-risk SLL is defined by the
presence of a 17p deletion or 11q deletion or TP53 mutation. Any CLL and SLL patient
who has a short remission duration of less than 3 years after prior first-line
chemo-immunotherapy, such as the FCR regimen, also fulfills criteria of high-risk
CLL/SLL, regardless of the presence or absence of cytogenetic abnormalities.

2. 2.CLL and SLL patients with 17p deletion or TP53 mutation will not be required to
have received any prior therapy, given the poor outcome of CLL/SLL patients to
standard frontline chemo-immunotherapy, such patients will be eligible if they are
untreated or if they have received up to 3 lines of prior therapy.

3. Patients must have an indication for treatment by 2008 IWCLL Criteria.

4. Patients age > 18 years at the time of signing informed consent. Understand and
voluntarily sign an informed consent. Be able to comply with study procedures and
follow-up examinations.

5. ECOG/WHO performance status of 0-1.

6. Patients of childbearing potential must be willing to practice highly effective birth
control (e.g., condoms, implants, injectables, combined oral contraceptives, some
intrauterine devices [IUDs], sexual abstinence, or sterilized partner) during the
study and for 30 days after the last dose of study drug. Women of childbearing
potential include any female who has experienced menarche and who has not undergone
successful surgical sterilization (hysterectomy, bilateral tubal ligation, or
bilateral oophorectomy) or is not postmenopausal. Post menopause is defined as
follows: Amenorrhea >/= 12 consecutive months without another cause and a documented
serum follicle stimulating hormone (FSH) level >35 mIU/mL; a male of childbearing
potential is any male that has not been surgically sterilized.

7. Adequate renal and hepatic function as indicated by all of the following: Total
bilirubin bilirubin elevation due to Gilbert's disease who will be allowed to participate; an
ALT 30 mL/min, as
calculated by the Cockcroft-Gault equation unless disease related.

8. Free of prior malignancies for 3 years with exception of currently treated basal
cell, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or
breast.

9. A Urine Pregnancy Test (within 7 days of Day 1) is required for women with
childbearing potential

Exclusion Criteria:

1. Pregnant or breast-feeding females.

2. Treatment including chemotherapy, chemo-immunotherapy , monoclonal antibody therapy,
radiotherapy, high-dose corticosteroid therapy (more than 60 mg prednisone or
equivalent daily), or immunotherapy within 21 days prior to enrollment or concurrent
with this trial.

3. Investigational agent received within 30 days prior to the first dose of study drug
or have previously taken PCI-32765. If received any investigational agent prior to
this time point, drug-related toxicities must have recovered to Grade 1 or less prior
to first dose of study drug.

4. Systemic fungal, bacterial, viral, or other infection not controlled (defined as
exhibiting ongoing signs/symptoms related to the infection and without improvement,
despite appropriate antibiotics or other treatment).

5. Patients with uncontrolled Autoimmune Hemolytic Anemia (AIHA) or autoimmune
thrombocytopenia (ITP).

6. Patients with severe hematopoietic insufficiency, as defined by an absolute
neutrophil count of less than 500/micro-L and/or a platelet count of less than
30,000/micro-L at time of screening for this protocol.

7. Any other severe concurrent disease, or have a history of serious organ dysfunction
or disease involving the heart, kidney, liver or other organ system that may place
the patient at undue risk to undergo therapy with PCI-32765 and rituximab.

8. Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias,
congestive heart failure, or myocardial infarction within 6 months of screening, or
any Class 3 or 4 cardiac disease as defined by the New York Heart Association
Functional Classification.

9. Significant screening ECG abnormalities including left bundle branch block, 2nd
degree AV block type II, 3rd degree block, bradycardia, and QTc > 470 msec.

10. Any serious medical condition, laboratory abnormality, or psychiatric illness that
places the subject at unacceptable risk if he/she were to participate in the study.

11. History of stroke or cerebral hemorrhage within 6 months.

12. Evidence of bleeding diathesis or coagulopathy.

13. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 1, anticipation of need for major surgical procedure during the course
of the study.

14. Minor surgical procedures, fine needle aspirations or core biopsies within 7 days
prior to Day 1. Bone marrow aspiration and/or biopsy are allowed.

15. Serious, non-healing wound, ulcer, or bone fracture.

16. Treatment with Coumadin. Patients who recently received Coumadin must be off Coumadin
for at least 7 days prior to start of the study.

17. Any chemotherapy (e.g., bendamustine, cyclophosphamide, pentostatin, or fludarabine),
immunotherapy (e.g., alemtuzumab, or ofatumumab), bone marrow transplant,
experimental therapy, or radiotherapy is prohibited during therapy on this study.

18. Use of medications known to prolong QTc interval or that may be associated with
Torsades de Pointes (refer to Appendix F) are prohibited within 7 days of starting
study drug and during study-drug treatment.

19. Requires treatment with strong CYP3A4/5 and/or CYP2D6 inhibitors.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression Free Survival (PFS)

Outcome Description:

Progression free survival defined as the time interval from treatment to progressive disease or death, whichever happens earlier. Patients in complete remission (CR), partial remission (PR) or stable disease (SD) are all counted as progression-free. Survival or times to progression functions estimated using the Kaplan-Meier method.

Outcome Time Frame:

3 months

Safety Issue:

Yes

Principal Investigator

Jan A. Burger, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2011-0785

NCT ID:

NCT01520519

Start Date:

February 2012

Completion Date:

Related Keywords:

  • Leukemia
  • Leukemia
  • Chronic Lymphocytic Leukemia
  • CLL
  • Small Lymphocytic Lymphoma
  • SLL
  • Rituximab
  • Rituxan
  • PCI-32765
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Lymphoma

Name

Location

UT MD Anderson Cancer Center Houston, Texas  77030