Study to Determine the Maximum Tolerated Dose, Safety and Effectiveness of Pomalidomide for Patients With Sickle Cell Disease (SCD-001)

A Prospective, Multi-Center, Open-Label, Dose-Escalation Study to Determine the Maximum Tolerated Dose, Safety and Effect on Induction of Fetal Hemoglobin of CC-4047 In Subjects With Sickle Cell Disease

The purpose of the study is to determine the maximum tolerated dose, safety and effect on induction of fetal hemoglobin of pomalidomide in patients with Sickle Cell Disease.

Study Overview

• Status: Completed
• Conditions: Anemia, Sickle Cell
• Intervention / Treatment: Drug: pomalidomide

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48201-2097
      • Karmanos Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ages 18 to 60 years, inclusive, at the time of signing the informed consent form
• Clinically significant Sickle Cell Disease (SCD) documented as Sickle Cell Anemia or Sickle Beta-Zero Thalassemia
• Clinically significant SCD defined as at least 1 documented pain episode per year averaged over the past 3 years or one episode of active leg ulcers, priapism, or acute chest syndrome over the past 3 years
• Failed to achieve at least an absolute 5% increase in hemoglobin F while taking Hydroxyurea (HU) or unable to tolerate HU as described by the treating physician and may include but is not limited to lack of efficacy (such as people who have continued to have pain episodes more than 2 times a year or who have had acute chest or multiorgan failure syndromes or an episode of priapism), or other severe side effects while on HU (severe side effects include significant myelosuppression; skin cancer; or cytotoxicity evidenced by gastrointestinal symptoms, dermatological reactions, hepatic enzyme elevations, pulmonary fibrosis or neurological disturbances), or refusal of hydroxyurea therapy by the informed patient
• Able to adhere to the study visit schedule and other protocol requirements
• Females must be surgically sterile (post hysterectomy or bilateral oophorectomy) or naturally postmenopausal for at least 24 consecutive months (i.e., have not had menses at any time in the preceding 24 consecutive months)
• Male subjects must agree to use a latex condom during any sexual contact with females of child bearing potential (FCBP) during study drug treatment, during dose interruptions, and for at least 28 days following discontinuation of study drug even if they have undergone a successful vasectomy. Counseling about the requirement for latex condom use during sexual contact with FCBP and the potential risks of fetal exposure must be conducted at a minimum of every 28 days.
• Male subjects must agree to abstain from donating semen or sperm while taking study drug and for 28 days after stopping study drug.
• Both males and females must agree to abstain from donating blood while taking study drug and for 28 days after stopping study drug.
• Both males and females must agree that they will not share study drug and will be counseled about the potential risks of fetal exposure.

Exclusion Criteria:

• Known positive status for human immune virus (HIV), Hepatitis B; or acute/chronic, active Hepatitis C
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
• Females of childbearing potential, pregnant or lactating females
• Any condition, including the presence of laboratory abnormalities, which place the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
• Subjects unlikely to comply with birth control, medication dosing, or study visit requirements
• Subjects with severe or life threatening, active, unresolved infections

• Any of the following laboratory abnormalities derived from the Screening Visit:

  • Platelet count or white blood cell count (WBC) less than the lower limit of normal (LLN)
  • Total hemoglobin less than or equal to 6.0 g/dL
  • Hemoglobin A (HbA) from transfusion greater than 20% at baseline
  • Creatinine greater than Upper Limit of Normal (ULN)
  • Alanine Aminotransferase / Serum Glutamic Pyruvic Transaminase (ALT/SGPT) greater than 3 x ULN
  • Total bilirubin greater than 10 mg/dL
• Subjects on a chronic transfusion program
• History of non-catheter related Deep Vein Thrombosis (DVT) or stroke
• Chronic symptomatic constipation
• History of cancer (except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix or breast) unless the subject has been free of disease for at least three years.
• Use of agents that can induce fetal hemoglobin within 90 days (three months) of Day 1 (i.e. HU, butyrates, decitabine, 5-azacytidine, or erythropoietin)
• Use of experimental drug or treatment within 30 days of the first dose of study drug
• History of allergic reaction to thalidomide or lenalidomide
• Prior desquamating (blistering) rash while taking thalidomide or lenalidomide
• Greater than or equal to a Grade 2 neuropathy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cohort 1: 0.5 mg pomalidomide; 0.5 mg pomalidomide orally daily for 84 days	Drug: pomalidomide; Pomalidomide orally for 84 days daily in doses ranging from 0.5 mg to 4.0 mg; Other Names: CC-4047
EXPERIMENTAL: Cohort 2: 1.0 mg pomalidomide; 1.0 mg pomalidomide orally daily for 84 days	Drug: pomalidomide; Pomalidomide orally for 84 days daily in doses ranging from 0.5 mg to 4.0 mg; Other Names: CC-4047
EXPERIMENTAL: Cohort 3: 2.0 mg pomalidomide; 2.0 mg pomalidomide orally daily for 84 days	Drug: pomalidomide; Pomalidomide orally for 84 days daily in doses ranging from 0.5 mg to 4.0 mg; Other Names: CC-4047
EXPERIMENTAL: Cohort 4: 3.0 mg pomalidomide; 3.0 mg pomalidomide orally daily for 84 days	Drug: pomalidomide; Pomalidomide orally for 84 days daily in doses ranging from 0.5 mg to 4.0 mg; Other Names: CC-4047
EXPERIMENTAL: Cohort 5: 4.0 mg pomalidomide; 4.0 mg pomalidomide orally daily for 84 days	Drug: pomalidomide; Pomalidomide orally for 84 days daily in doses ranging from 0.5 mg to 4.0 mg; Other Names: CC-4047

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD)	Maximum Tolerated Dose	Up to 84 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Type, frequency, and severity of adverse events, and relationship of adverse events to pomalidomide	Up to 169 days
Absolute fetal hemoglobin change	Percent of subjects with an absolute increase of 5% in percent fetal hemoglobin levels during study treatment	UP to 169 days
% total hemoglobin	Percent change in total hemoglobin from baseline to highest level	Up to 169 days
Rate of total hemoglobin change	Rate of change of total hemoglobin from baseline to highest level	Up to 169 days
Inflammation markers and cytokines	Change in serum inflammation markers and cytokines from baseline, during and at end of study treatment	Up to 169 days

Collaborators and Investigators

• Sponsor: Celgene

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2007
• Primary Completion (ACTUAL): October 1, 2012
• Study Completion (ACTUAL): December 1, 2013

Study Registration Dates

• First Submitted: January 27, 2012
• First Submitted That Met QC Criteria: January 27, 2012
• First Posted (ESTIMATE): January 31, 2012

Study Record Updates

• Last Update Posted (ACTUAL): November 8, 2019
• Last Update Submitted That Met QC Criteria: November 6, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Pomalidomide; Sickle Cell Disease; Fetal Hemoglobin
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Pomalidomide
• Other Study ID Numbers: CC-4047-SCD-001