Phase I Study to Determine the Safety and Tolerability of Escalating Doses of Panobinostat (LBH589) in Patients With Sickle Cell Disease


1 United States site


> 18 Years




Phase 1

Study type








About the study

The goal of this clinical research study is to find out about the safety and effects of a
drug called panobinostat when given to adults with sickle cell disease. Panobinostat is a pan
histone deacetylase (HDAC) inhibitor. HDAC inhibitors have been shown to significantly
increase hemoglobin F induction, which is well documented to improve outcomes in sickle cell
disease. HDAC inhibitors are also known to potently inhibit cell-specific inflammation, which
is a primary contributor to the debilitating effects of sickle cell disease. Given the
relevance of these mechanisms of action in SCD, panobinostat may prove to contribute
significantly to the management of SCD patients, a population in critical need of further
effective treatment options.

participation requirements

1. Male or female patients ages ≥ 18 years

2. Confirmed diagnosis of homozygous SS or S-β0Thalassemia

3. Intolerance to hydroxyurea therapy, refusal of hydroxyurea therapy, or failure to
respond (refractoriness) to hydroxyurea therapy, either clinically or hematologically.

4. Clinically significant sickle cell disease as defined by:

1. At least two hospitalizations over the past twelve months for any complication of
sickle cell disease; or

2. At least three pain crises over the past twelve months that last four or more
hours and require a visit to a medical facility for treatment with oral or
parenteral narcotics; or

3. History of recurrent leg ulcers; or

4. History of Acute Chest Syndrome within the past five years; or

5. History of priapism requiring medical intervention within the past two years; or

6. History of stroke (but not currently on a chronic blood transfusion regimen).

5. Ability to provide written informed consent obtained prior to participation in the
study and any related procedures being performed.

6. Clinically euthyroid. Note: Patients are permitted to receive thyroid hormone
supplements to treat underlying hypothyroidism.

participation restrictions

1. Use of agents that can induce Hb F within 60 days of Day 1 (i.e. hydroxyurea,
butyrates, decitabine, 5-azacytidine, IMiDs®, or erythropoietin). Prior use of HDACi,
including panobinostat, is not an exclusion criterion if discontinued > 60 days.

2. Patients who have had a vaso-occlusive crisis within the past 2 weeks that required
treatment with parenteral medication.

3. Impairment of GI function or GI disease that may significantly alter the absorption of
panobinostat (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea,
malabsorption syndrome, or small bowel resection)

4. Patients on a chronic transfusion regimen, or any patient who has Hb A% > 20% from a
recent transfusion

5. Any of the following laboratory abnormalities derived from the screening visit:

– Absolute neutrophil count (ANC) < 1.5 x 109/L - Hemoglobin < 6 g/dl - Platelets < 100x 109/L - Serum creatinine >1.5 x Upper limits of normal (ULN)

– AST and ALT > 2.5 x ULN

– Serum total bilirubin > 10 mg/dL

– Serum direct bilirubin > 1 mg/dL

– Albumin <3.0 g/dl - Serum potassium < Lower limits of normal (LLN) - Total serum calcium [corrected for serum albumin] or ionized calcium 100 bpm).
Patients with stable atrial fibrillation are eligible, provided they do not meet
any of the other cardiac exclusion criteria.

– Clinically significant resting bradycardia (< 50 bpm) - QTc > 470 msec on screening ECG

– Right bundle branch block + left anterior hemiblock (bifasicular block)

– Angina pectoris 3 months prior to starting study drug

– Acute MI 3 months prior to starting study drug

– Other clinically significant heart disease (e.g., CHF, uncontrolled hypertension,
history of labile hypertension, or history of poor compliance with an
antihypertensive regimen)

7. Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled
diabetes, active or uncontrolled infection, chronic obstructive or chronic restrictive
pulmonary disease) that could cause unacceptable safety risks or compromise compliance
with the protocol

8. Patients who are currently receiving treatment with any study drug or have been on any
study medications within the past 60 days.

9. Patients who have undergone major surgery 2 weeks prior to starting study drug or who
have not recovered from side effects of such therapy.

10. Women of child-bearing potential (WCBP) who are pregnant or breast feeding or who do
not agree to use two methods of birth control, including a barrier method, if they are
sexually active. WCBP, defined as sexually mature women who have not undergone a
hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive
months (i.e., who has had menses any time in the preceding 12 consecutive months),
must have a negative serum pregnancy test at screening and negative urine pregnancy
test within 72 hours prior to starting study treatment. In addition, all sexually
active WCBP must agree to use double method of contraception (oral, injectable, or
implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier
contraceptive with spermicide; or vasectomized partner) during the study and 3 months
after the end of treatment. One of these methods of contraception must be a barrier

11. Male patients whose sexual partners are WCBP not using a double method of
contraception during and 3 months after the end of treatment. Males must agree to use
a condom during any sexual contact with WCBP during study drug treatment, during dose
interruptions, and for 3 months after the end of treatment.

12. Known diagnosis of HIV infection, Hepatitis B; or acute/chronic, active Hepatitis C

13. Patients with a prior malignancy with in the last 5 years (except for basal or
squamous cell carcinoma, or in situ cancer of the cervix)

14. Patients with any significant history of non-compliance to medical regimens or
unwilling or unable to comply with the instructions given to him/her by the study

15. Patients who are currently receiving treatment with certain prohibited medications and
cannot either discontinue this treatment or switch to a different medication prior to
study enrollment.


  • Augusta, Georgia, United States, Augusta University, 30912