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A Study of BBI608 in Adult Patients With Advanced, Refractory Hematologic Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02352558
Recruitment Status : Completed
First Posted : February 2, 2015
Last Update Posted : October 1, 2019
Sponsor:
Information provided by (Responsible Party):
Sumitomo Dainippon Pharma Oncology, Inc

Brief Summary:
This is a multicenter, open label, Phase 1 dose-escalation study of BBI608 administered to patients with relapsed, refractory hematologic malignancies, including multiple myeloma, lymphoma, and others.

Condition or disease Intervention/treatment Phase
Hematologic Malignancy Drug: BBI608 Drug: Dexamethasone Drug: Bortezomib Drug: Imatinib Drug: Ibrutinib Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib Clinical Study of BBI608 for Adult Patients With Advanced, Refractory Hematologic Malignancies
Study Start Date : May 2015
Actual Primary Completion Date : December 14, 2018
Actual Study Completion Date : May 16, 2019


Arm Intervention/treatment
Experimental: Arm 1
Patients with multiple myeloma treated with BBI608
Drug: BBI608
Patients will receive BBI608 orally twice daily, with doses separated by approximately 12 hours. The starting dose for all cohorts will be 240 mg twice daily. Subsequently, cohorts at alternate dose-levels (480 mg twice daily) may be enrolled as determined by the criteria for dose-escalation.
Other Names:
  • Napabucasin
  • BB608
  • BBI-608

Experimental: Arm 2
Patients with lymphoma treated with BBI608
Drug: BBI608
Patients will receive BBI608 orally twice daily, with doses separated by approximately 12 hours. The starting dose for all cohorts will be 240 mg twice daily. Subsequently, cohorts at alternate dose-levels (480 mg twice daily) may be enrolled as determined by the criteria for dose-escalation.
Other Names:
  • Napabucasin
  • BB608
  • BBI-608

Experimental: Arm 3
Patients with acute myeloid leukemia or myelo-dysplastic syndrome treated with BBI608
Drug: BBI608
Patients will receive BBI608 orally twice daily, with doses separated by approximately 12 hours. The starting dose for all cohorts will be 240 mg twice daily. Subsequently, cohorts at alternate dose-levels (480 mg twice daily) may be enrolled as determined by the criteria for dose-escalation.
Other Names:
  • Napabucasin
  • BB608
  • BBI-608

Experimental: Arm 4
Patients with chronic myeloid leukemia treated with BBI608
Drug: BBI608
Patients will receive BBI608 orally twice daily, with doses separated by approximately 12 hours. The starting dose for all cohorts will be 240 mg twice daily. Subsequently, cohorts at alternate dose-levels (480 mg twice daily) may be enrolled as determined by the criteria for dose-escalation.
Other Names:
  • Napabucasin
  • BB608
  • BBI-608

Experimental: Arm 5
Patients with multiple myeloma treated with BBI608 and dexamethasone
Drug: BBI608
Patients will receive BBI608 orally twice daily, with doses separated by approximately 12 hours. The starting dose for all cohorts will be 240 mg twice daily. Subsequently, cohorts at alternate dose-levels (480 mg twice daily) may be enrolled as determined by the criteria for dose-escalation.
Other Names:
  • Napabucasin
  • BB608
  • BBI-608

Drug: Dexamethasone
Dexamethasone will be taken orally at a dose level of 40 mg once weekly, on Days 1, 8, 15, and 22 of each Cycle. Patients over the age of 75 years are allowed to begin dexamethasone at a dose of 20 mg once weekly, on Days 1, 8, 15, and 22 of each Cycle. Dexamethasone should be taken with food or milk, and a minimum of 2 hours should separate a dose of dexamethasone from a dose of BBI608.

Experimental: Arm 6
Patients with multiple myeloma treated with BBI608 and bortezomib
Drug: BBI608
Patients will receive BBI608 orally twice daily, with doses separated by approximately 12 hours. The starting dose for all cohorts will be 240 mg twice daily. Subsequently, cohorts at alternate dose-levels (480 mg twice daily) may be enrolled as determined by the criteria for dose-escalation.
Other Names:
  • Napabucasin
  • BB608
  • BBI-608

Drug: Bortezomib
Bortezomib will be administered at 1.3 mg/m2/dose as a 3-5 second bolus intravenous (IV) injection or subcutaneous injection twice weekly for 2 weeks (Day 1, 4, 8, and 11) followed by a 10-day rest period (Day 12-21).
Other Name: Velcade

Experimental: Arm 7
Patients with chronic myeloid leukemia treated with BBI608 and imatinib
Drug: BBI608
Patients will receive BBI608 orally twice daily, with doses separated by approximately 12 hours. The starting dose for all cohorts will be 240 mg twice daily. Subsequently, cohorts at alternate dose-levels (480 mg twice daily) may be enrolled as determined by the criteria for dose-escalation.
Other Names:
  • Napabucasin
  • BB608
  • BBI-608

Drug: Imatinib
Imatinib will be taken orally once daily with a meal and a large glass of water. For patients having difficulty swallowing, imatinib can be dissolved in water or apple juice for intake. The dose of imatinib is 400 mg for CML patients in the chronic phase and 600 mg for CML patients in the accelerated phase or in blast crisis. A minimum of 2 hours should separate a dose of imatinib from a dose of BBI608.
Other Name: Gleevec

Experimental: Arm 8
Patients with chronic lymphocytic leukemia treated with BBI608
Drug: BBI608
Patients will receive BBI608 orally twice daily, with doses separated by approximately 12 hours. The starting dose for all cohorts will be 240 mg twice daily. Subsequently, cohorts at alternate dose-levels (480 mg twice daily) may be enrolled as determined by the criteria for dose-escalation.
Other Names:
  • Napabucasin
  • BB608
  • BBI-608

Experimental: Arm 9
Patients with chronic lymphocytic leukemia treated with BBI608 and ibrutinib
Drug: BBI608
Patients will receive BBI608 orally twice daily, with doses separated by approximately 12 hours. The starting dose for all cohorts will be 240 mg twice daily. Subsequently, cohorts at alternate dose-levels (480 mg twice daily) may be enrolled as determined by the criteria for dose-escalation.
Other Names:
  • Napabucasin
  • BB608
  • BBI-608

Drug: Ibrutinib
Ibrutinib will be taken orally once daily with water. Do not open, break, or chew the capsules. The dose of ibrutinib is 420 mg for patients with normal liver function and is 140 mg for patients with mild liver impairment (Child-Pugh class A). A minimum of 2 hours should separate a dose of ibrutinib from a dose of BBI608.
Other Name: Imbruvica




Primary Outcome Measures :
  1. Determination of the safety and tolerability of BBI608 administered as monotherapy and in combination with dexamethasone, bortezomib, imatinib or ibrutinib by assessing dose-limiting toxicities (DLTs) [ Time Frame: 4 weeks ]

Secondary Outcome Measures :
  1. Pharmacokinetic profile of BBI608 when administered in monotherapy and in combination with dexamethasone, bortezomib, imatinib or ibrutinib as assessed by maximum plasma concentration and area under the curve [ Time Frame: -5min, 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, 11, 12 hours on day 1, cycles 1 and 2 ]
  2. Pharmacodynamic activity of BBI608 when administered in monotherapy and in combination with dexamethasone, bortezomib, imatinib or ibrutinib as assessed by biomarker analysis [ Time Frame: 20 weeks ]
    Histopathology and Cancer Stem Cell assays will be performed to provide information of the biomarkers on patient blood samples collected on-study, as well as on (if available) bone marrow, other biopsied patient tumor tissue, and archival samples.

  3. Assessment of the preliminary anti-tumor activity by performing tumor assessments [ Time Frame: 20 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Major Inclusion Criteria:

  1. Signed written informed consent must be obtained and documented according to the International Conference on Harmonisation (ICH) and be in accordance with local regulatory requirements
  2. A histologically confirmed hematologic malignancy that is advanced, relapsed, or refractory to standard, currently available anti-cancer treatment options
  3. ≥ 18 years of age
  4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 at dose escalation phase and of ≤ 2 at dose expansion phase
  5. Male or female patients of child-producing potential must agree to use contraception or avoidance of pregnancy measures during the study and for 30 days after their last dose
  6. Females of childbearing potential must have a negative serum pregnancy test
  7. Aspartate transaminase (AST) ≤ 2.5 x upper limit of normal (ULN) and alanine transaminase (ALT) ≤ 2.5 × upper limit of normal (ULN). Patients whose disease involves the liver and who have laboratory values of AST ≤ 3.5 ULN, AST ≤ 3.5 ULN, and albumin ≥ 35g/L may be enrolled if agreed upon by the Principal Investigator and Medical Monitor for the Sponsor
  8. Total bilirubin < 1.5 x ULN, except for cases in which elevation of total bilirubin is due to elevated levels of unconjugated bilirubin consistent with a diagnosis of Gilbert's Syndrome
  9. Life expectancy ≥ 3 months

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02352558


Locations
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United States, Colorado
Rocky Mountain Cancer Centers
Denver, Colorado, United States, 80218
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Tennessee
West Clinic
Germantown, Tennessee, United States, 38138
United States, Texas
Cancer Care Centers of South Texas
San Antonio, Texas, United States, 78217
Cancer Care Centers of South Texas - HOAST
San Antonio, Texas, United States, 78229
United States, Virginia
Virginia Cancer Specialists, P.C.
Fairfax, Virginia, United States, 22031
Virginia Oncology Associates
Norfolk, Virginia, United States, 23502
United States, Washington
Northwest Cancer Specialists, PC
Vancouver, Washington, United States, 98684
Sponsors and Collaborators
Sumitomo Dainippon Pharma Oncology, Inc
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Responsible Party: Sumitomo Dainippon Pharma Oncology, Inc
ClinicalTrials.gov Identifier: NCT02352558    
Other Study ID Numbers: BBI608-103HEME
BBI608-103HEM ( Other Identifier: Boston Biomedical, Inc. )
First Posted: February 2, 2015    Key Record Dates
Last Update Posted: October 1, 2019
Last Verified: September 2019
Keywords provided by Sumitomo Dainippon Pharma Oncology, Inc:
Multiple Myeloma
Lymphoma
Acute Myeloid Leukemia
Myelo-Dysplastic Syndrome
Chronic Myeloid Leukemia
Chronic Lymphocytic Leukemia
Additional relevant MeSH terms:
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Hematologic Neoplasms
Neoplasms
Neoplasms by Site
Hematologic Diseases
Dexamethasone
Bortezomib
Imatinib Mesylate
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action