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Lymphoma, T-CellPhase 1NCT04233697

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

A Phase 1 study testing Copanlisib and Romidepsin in people with Lymphoma, T-Cell, run by Columbia University.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma, T-Cell
What is being tested?
Copanlisib and Romidepsin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Feb 2020to 30 Jul 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • Patients with uncontrolled inter-current illness (e.g. pneumonia).
  • Patients with known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies
  • Adequate Contraception.

Who cannot join

  • 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.
Show all 36Show fewer
  • 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.
  • Patients with uncontrolled inter-current illness (e.g. pneumonia).
  • Patients with known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies
  • Patients with known active concurrent malignancy (except non-melanoma skin cancer, prostatic intraepithelial neoplasia, or carcinoma in situ of the cervix). If there is a history of prior malignancy, the patient must be disease-free for ≥ 3 years.
  • Patients with known active central nervous system (CNS) metastases and/or carcinomatous meningitis and/or known lymphomatous involvement of the central nervous system.
  • Evidence of active non-infectious pneumonitis (NIP).
  • History of concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator).
  • Patients with an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Of note, replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed for patient on study.
  • Uncontrolled Type I or II diabetes mellitus as deemed appropriate by the investigator (suggested guidelines for uncontrolled diabetes: HbA1c> 8.5%).
  • Uncontrolled hypertension, i.e., blood pressure (BP) of ≥ 150/90; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria.
  • Concomitant use of CYP3A4 inhibitors.
  • Congenital long QT syndrome and/or QTc interval ≥ 500 milliseconds.
  • Patients taking drugs leading to significant QT prolongation.
  • Any cardiac arrhythmia requiring an anti-arrhythmic medication, with the exception of stable doses of beta-blockers.
  • Myocardial infarction within 6 months of cycle 1, day 1. [Subjects with a history of myocardial infarction between 6 and 12 months prior to cycle 1, day 1, who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event, may participate].
  • Symptomatic coronary artery disease (CAD), e.g., angina Canadian Class II-IV. In any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present.
  • An ECG recorded at screening showing evidence of cardiac ischemia (ST depression of ≥ 2 mm, measured from isoelectric line to the ST segment). If in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present.
  • Congestive heart failure (CHF) that meets New York Heart Association (NYHA) Class II to IV definitions and/or ejection fraction < 40% by multigated acquisition (MUGA) scan or < 50% by echocardiogram and/or magnetic resonance imaging (MRI);
  • Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes.
  • Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before the start of study medication.
  • Patients requiring dual anti-platelets treatment for cardiac conditions or patients who are on anticoagulation for arterial or venous thrombosis. Patients with known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Patients that are pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through at least 30 days after the last dose of trial treatment.

About this study

Official title: Phase 1B Study of the PI3K Inhibitor Copanlisib in Combination With Romidepsin in the Treatment of Patients With Relapsed or Refractory Mature T-cell Lymphoma

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.

Read the detailed description

The non-Hodgkin lymphomas (NHL) represent 4-5% of all new cancer cases, and is the seventh leading cause of cancer death. In 2015, there were an estimated 71,850 cases in the United States, and approximately 19,790 deaths. An evaluation of the distribution of NHL sub-types was performed on 114,548 cases of lymphoid neoplasms diagnosed between 1992-2001 and reported to the Surveillance Epidemiology and End Results (SEER) registry. Of all NHL, 87,666 were B-cell lymphoid neoplasms, and 6,228 were considered T/Natural Killer (NK) cell neoplasms.

The peripheral T-cell lymphomas (PTCL) are a heterogeneous group of aggressive lymphoid neoplasms and account for 10-15% of all newly diagnosed cases of NHL. The current prevalence of PTCL in the United States is estimated to be approximately 9,500 patients. PTCL-Not Otherwise Specified (NOS), a nodal subtype, is the most common T-cell lymphoma in the United States and Europe. PTCL is associated with a significantly worse prognosis compared to its B-cell counterparts. Treatment options for patients with relapsed/refractory (R/R) PTCL have been limited. The addition of novel drugs to conventional chemotherapy has largely proven unsuccessful. Since 2009, new drugs have entered the therapeutic field for patients with R/R PTCL.

Pralatrexate was the first drug approved for patients with R/R PTCL. Other drugs approved for patients with R/R PTCL include romidepsin and belinostat. These agents appear to exhibit lineage-specific activity in PTCL. Over the past few years, the investigators have focused on exploring rational combinations of these T-cell active agents in an effort to develop novel treatment platforms. Early clinical studies of these combinations have shown very promising activity.

Being tested
Copanlisib, Romidepsin
Keywords
Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), Copanlisib, Romidepsin
Medical subject headings
Lymphoma, T-Cell, Hodgkin Disease, Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CopanlisibDrug

    Also called Aliqopa, 80-6946

    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.

  • RomidepsinDrug

    Also called Istodax

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

Study groups in NCT04233697
Study groupRoleWhat they receive
Copanlisib and RomidepsinExperimentalCopanlisib 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".
Receives: Drug: Copanlisib; Drug: Romidepsin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jan 2020
  2. Study startFeb 2020 (estimated)
  3. Primary completion30 Jul 2022 (estimated)
  4. Study completion30 Jul 2023 (estimated)

Why it stopped: Investigator left institution

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04233697
Sponsor's protocol ID
AAAR5207
Status last verified
Aug 2020
First submitted
15 Jan 2020
Last updated
13 Aug 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Copanlisib and Romidepsin in people with Lymphoma, T-Cell, run by Columbia University.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 13 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose (MTD) (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04233697.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2020.

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