Carfilzomib Plus Belinostat in Relapsed/Refractory NHL

NCT02142530 | Completed Phase 1 DMC

• 1 other identifier: 14-096
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 3

Brief Summary

This research study is evaluating a drug called carfilzomib used in combination with another drug called belinostat with participants who have relapsed or refractory non-Hodgkin lymphoma (NHL).

Conditions

Non-Hodgkin Lymphoma; Diffuse Large B-cell Lymphoma; Mantle Cell Lymphoma; Follicular Lymphoma; Peripheral T-cell Lymphoma

Keywords

NHL; DLBCL; PTCL; Marginal zone lymphoma; lymphoplasmacytic lymphoma; Waldenstrom's macroglobulinemia

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated doses of carfilzomib and belinostat in combination

  Baseline, 28 days

Secondary Outcomes (3)

• Number of Participants with Serious Adverse Events

  28 days

• Plasma Concentration Time Profiles

  0, 5, 15, 30, 60, 90 min and 2, 4, 6, 8, and 24 hours

• Objective response rate

  8 Weeks

Study Arms (1)

Carfilzomib/ Belinostat

EXPERIMENTAL

Carfilzomib and Belinostat will be administered on a 28-day schedule. * Carfilzomib will be given on days 1-2, 8-9, and 15-16 of each cycle, beginning at a dose of 20 mg/m2 (dose level 0). * Belinostat will be given on days 1-5 beginning at a dose of 600 mg/m2. * Belinostat dosing will precede carfilzomib dosing on days when both drugs are administered. In dose level 1 and beyond, carfilzomib will be given at a dose of 20mg/m2 with cycle 1, and then escalated with cycle 2 * A maximum of four dose levels are planned with carfilzomib escalated no higher than 20/36 mg/m2 and belinostat escalated no higher than 900 mg/m2.

Drug: Carfilzomib; Drug: Belinostat

Interventions

Carfilzomib DRUG

Also known as: Kyprolis®

Carfilzomib/ Belinostat

Belinostat DRUG

Also known as: Beleodaq

Carfilzomib/ Belinostat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have histologically confirmed relapsed or refractory non-Hodgkin lymphoma that is not a candidate for standard curative therapy. NHL subtypes include: Diffuse large B-cell lymphoma (DLBCL), Mantle cell lymphoma, Marginal zone lymphoma, Lymphoplasmacytic lymphoma, Peripheral T-cell lymphomas, and Follicular lymphoma of any grade.
• Patients must have received at least one prior systemic therapy for lymphoma. A washout period of at least 3 weeks is required from the most recent prior therapy.
• Age ≥18 years
• ECOG performance status ≤ 2 (Karnofsky ≥ 60%, see Appendix A)
• Participants must have organ and marrow function as defined below:
• absolute neutrophil count ≥1,000/mcL
• platelets ≥75,000/mcL
• total bilirubin ≤ 2 × institutional upper limit of normal
• AST(SGOT)/ALT(SGPT) ≤ 3 × institutional upper limit of normal
• creatinine ≤1.5 × institutional upper limit of normal
• \--- OR
• creatinine clearance ≥45 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
• Participants may have either measurable or non-measurable disease, but in all cases eligible patients must have disease that can be clinically evaluated for improvement or progression.
• Patients must have fully recovered from major surgery and from the acute toxic effects of prior chemotherapy and radiotherapy (residual grade 1 toxicity, e.g., grade 1 peripheral neuropathy, and residual alopecia are allowed).
• The effects of carfilzomib and belinostat on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of study drug administration.

You may not qualify if:

• Participants who have had chemotherapy or radiotherapy within 3 weeks (8 weeks for radioimmunotherapy) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier.
• Participants who are receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to carfilzomib or belinostat
• Patients with a systemic fungal, bacterial, viral, or other infection not controlled
• Pregnant or lactating patients.
• Prior history of another malignancy (except for non-melanoma skin cancer, in situ cervical or breast cancer, or prostate cancer detectable only by PSA) unless disease free for over one year
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Congestive heart failure of any severity (NYHA class I-IV)
• Any active angina or any unstable angina pectoris or myocardial infarction within one year of study entry.
• Left ventricular ejection fraction below the lower limit of normal
• Greater than grade 1 peripheral neuropathy at baseline
• Congenital long QT syndrome or history of torsades de pointes
• Baseline QTc interval \> 500 msec
• Concomitant medications required on dosing days that increase risk of torsades de pointes
• Subjects with known HIV infection

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Comprehensive Cancer Network: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth-Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Lymphoma, Follicular; Lymphoma, T-Cell, Peripheral; Lymphoma, B-Cell, Marginal Zone; Waldenstrom Macroglobulinemia

Interventions

carfilzomib; belinostat

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Lymphoma, T-Cell; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders

Study Officials

• Jeremy Abramson, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 16, 2014
• First Posted: May 20, 2014
• Study Start: October 1, 2014
• Primary Completion: March 1, 2017
• Study Completion: January 1, 2018
• Last Updated: January 25, 2018

Record last verified: 2018-01

Locations

US (3)