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

Hematologic Malignancy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02352558
• Other study ID #: BBI608-103HEME
• Secondary ID: BBI608-103HEM
• Status: Completed
• Phase: Phase 1
• Start date: May 2015
• Est. completion date: May 16, 2019

Study information

• Verified date: November 2023
• Source: Sumitomo Pharma America, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: May 16, 2019
• Est. primary completion date: December 14, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hematologic Malignancy
• Hematologic Neoplasms
• Neoplasms

Intervention

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.
• 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.
• 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).
• 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.
• 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.

Locations

Country	Name	City	State
United States	Rocky Mountain Cancer Centers	Denver	Colorado
United States	Virginia Cancer Specialists, P.C.	Fairfax	Virginia
United States	West Clinic	Germantown	Tennessee
United States	Indiana University	Indianapolis	Indiana
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Cancer Care Centers of South Texas	San Antonio	Texas
United States	Cancer Care Centers of South Texas - HOAST	San Antonio	Texas
United States	Northwest Cancer Specialists, PC	Vancouver	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Sumitomo Pharma America, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Assessment of the preliminary anti-tumor activity by performing tumor assessments		20 weeks