Copanlisib in Combination With Romidepsin in Patients With Relapsed or Refractory Mature T-cell Lymphoma

NCT04233697 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: AAAR5207
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is an open label, Phase IB dose-escalation study of the PI3K inhibitor copanlisib in combination with romidepsin in patients with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL). The primary objective of the phase I study is to determine the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), and dose limiting toxicities (DLTs) of the combination of copanlisib and romidepsin in patients with R/R, NHL or HL.

Conditions

Lymphoma, T-Cell

Keywords

Hodgkin lymphoma (HL); non-Hodgkin lymphoma (NHL); Copanlisib; Romidepsin

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  The estimated MTD would be the highest dose at which 0 out of 3 or 1 out of 6 subjects experience a dose-limiting toxicity (DLT), i.e. dose with an observed DLT rate of less than 0.33.

  2 years

Study Arms (1)

Copanlisib and Romidepsin

EXPERIMENTAL

Copanlisib and romidepsin will be both administered via IV (through a vein in arm) on days 1, 8, and 15 every 28 days, also called a "cycle".

Drug: Copanlisib; Drug: Romidepsin

Interventions

Copanlisib DRUG

Novel, pan-class phosphatidylinositol 3-kinase (PI3K) inhibitor with potent activity against both the δ and α isoforms9. Copanlisib has been evaluated for the treatment of a wide variety of malignancies, including lymphoma, either as a single agent or in combination with other investigational agents.

Also known as: Aliqopa, 80-6946

Copanlisib and Romidepsin

Romidepsin DRUG

Indicated for treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy.

Also known as: Istodax

Copanlisib and Romidepsin

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent for the trial.
• Be ≥18 years of age on day of signing informed consent.
• Have measurable disease based on the Lugano Criteria.
• Phase I: patient must have histologically confirmed R/R NHL or HL (defined by World Health Organization (WHO) criteria).
• Expansion phase: patients must have histologically confirmed R/R mature T-cell lymphoma (defined by WHO criteria).
• Patient must have received at least two prior lines of therapy prior to enrollment in this study.
• Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Left Ventricular Ejection Fraction (LVEF) \> 50%.
• Demonstrate adequate organ function. All screening labs should be performed within 10 days of treatment initiation. The following treatments are prohibited: (a) Chemotherapy, monoclonal antibody within 4 weeks; (b) radiotherapy within 2 weeks prior to entering the study; (c) systemic steroids that have not been stabilized (≥ 5 days) to the equivalent of ≤10 mg/day prednisone prior to the start of the study drugs; (d) other concurrent investigational agents within 4 weeks prior to entering the study; (e) use of copanlisib or romidepsin within the past 3 months.
• Patients that have not recovered from adverse events due to chemotherapy agents administered more than 4 weeks earlier.
• Hypersensitivity to copanlisib or romidepsin or any of its excipients.
• Patients that received major surgery and have not recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Patients with active, clinically serious infections \> CTCAE Grade 2.
• Patients with Cytomegalovirus (CMV) PCR positive at baseline.
• Patients with active infections including: active tuberculosis (TB), Hepatitis B (e.g., HBsAg reactive), Hepatitis C, Hepatitis A.

You may not qualify if:

• The following treatments are prohibited: (a) Chemotherapy, monoclonal antibody within 4 weeks; (b) radiotherapy within 2 weeks prior to entering the study; (c) systemic steroids that have not been stabilized (≥ 5 days) to the equivalent of ≤10 mg/day prednisone prior to the start of the study drugs; (d) other concurrent investigational agents within 4 weeks prior to entering the study; (e) use of copanlisib or romidepsin within the past 3 months.
• Patients that have not recovered from adverse events due to chemotherapy agents administered more than 4 weeks earlier.
• Hypersensitivity to copanlisib or romidepsin or any of its excipients.
• Patients that received major surgery and have not recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Patients with active, clinically serious infections \> CTCAE Grade 2.
• Patients with CMV PCR positive at baseline.
• Patients with active infections including: active TB (Mycobacterium Tuberculosis), Hepatitis B (e.g., HBsAg reactive), Hepatitis C (e.g., HCV RNA \[qualitative\] is detected), Hepatitis A.
• Patients with uncontrolled inter-current illness (e.g. pneumonia).
• Patients with known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies The following treatments are prohibited: (a) Chemotherapy, monoclonal antibody within 4 weeks; (b) radiotherapy within 2 weeks prior to entering the study; (c) systemic steroids that have not been stabilized (≥ 5 days) to the equivalent of ≤10 mg/day prednisone prior to the start of the study drugs; (d) other concurrent investigational agents within 4 weeks prior to entering the study; (e) use of copanlisib or romidepsin within the past 3 months.
• Patients that have not recovered from adverse events due to chemotherapy agents administered more than 4 weeks earlier.
• Hypersensitivity to copanlisib or romidepsin or any of its excipients.
• Patients that received major surgery and have not recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Patients with active, clinically serious infections \> CTCAE Grade 2.
• Patients with CMV PCR positive at baseline.
• Patients with active infections including: active TB (Mycobacterium Tuberculosis), Hepatitis B (e.g., HBsAg reactive), Hepatitis C (e.g., HCV RNA \[qualitative\] is detected), Hepatitis A.

Sponsors & Collaborators

• Columbia University: lead
• Bayer: collaborator

MeSH Terms

Conditions

Lymphoma, T-Cell; Hodgkin Disease; Lymphoma, Non-Hodgkin

Interventions

copanlisib; romidepsin

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Changchun Deng, MD, PhD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2020
• First Posted: January 18, 2020
• Study Start: February 1, 2020
• Primary Completion: July 30, 2022
• Study Completion: July 30, 2023
• Last Updated: August 13, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share