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

A Phase Ib Clinical Study of BBI608 for Adult Patients With Advanced, Refractory Hematologic Malignancies

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.

Study Overview

• Status: Completed
• Conditions: Hematologic Malignancy
• Intervention / Treatment: Drug: BBI608; Drug: Dexamethasone; Drug: Bortezomib; Drug: Imatinib; Drug: Ibrutinib

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Centers
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • West Clinic
  • Texas
    • San Antonio, Texas, United States, 78217
      • Cancer Care Centers of South Texas
    • San Antonio, Texas, United States, 78229
      • Cancer Care Centers of South Texas - HOAST
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists, P.C.
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates
  • Washington
    • Vancouver, Washington, United States, 98684
      • Northwest Cancer Specialists, PC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / 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; BBI-608; BB608
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; BBI-608; BB608
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; BBI-608; BB608
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; BBI-608; BB608
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; BBI-608; BB608; 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; BBI-608; BB608; 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 Names: 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; BBI-608; BB608; 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 Names: 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; BBI-608; BB608
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; BBI-608; BB608; 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 Names: Imbruvica

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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)	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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		-5min, 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 8, 11, 12 hours on day 1, cycles 1 and 2
Pharmacodynamic activity of BBI608 when administered in monotherapy and in combination with dexamethasone, bortezomib, imatinib or ibrutinib as assessed by biomarker analysis	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.	20 weeks
Assessment of the preliminary anti-tumor activity by performing tumor assessments		20 weeks

Collaborators and Investigators

• Sponsor: Sumitomo Pharma America, Inc.

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): December 14, 2018
• Study Completion (Actual): May 16, 2019

Study Registration Dates

• First Submitted: January 26, 2015
• First Submitted That Met QC Criteria: January 28, 2015
• First Posted (Estimated): February 2, 2015

Study Record Updates

• Last Update Posted (Actual): November 14, 2023
• Last Update Submitted That Met QC Criteria: November 13, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; Multiple Myeloma; Lymphoma; Chronic Myeloid Leukemia; Chronic Lymphocytic Leukemia; Myelo-Dysplastic Syndrome
• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protein Kinase Inhibitors; Dexamethasone; Bortezomib; Imatinib Mesylate
• Other Study ID Numbers: BBI608-103HEME; BBI608-103HEM (Other Identifier: Sumitomo Dainippon Pharma Oncology, Inc.)