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Copanlisib and Venetoclax for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma

Primary Purpose

Recurrent Mantle Cell Lymphoma, Refractory Mantle Cell Lymphoma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Copanlisib Hydrochloride
Venetoclax
Sponsored by
City of Hope Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Mantle Cell Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Documented informed consent of the participant and/or legally authorized representative

    • Assent, when appropriate, will be obtained per institutional guidelines
  • Agreement to allow the use of archival tissue from diagnostic tumor biopsies

    • If unavailable, exceptions may be granted with study principal investigator (PI) approval
  • Age: >= 18 years
  • Eastern Cooperative Oncology Group (ECOG) =< 2
  • Life expectancy >= 3 months (per physician assessment)
  • Ability to take oral medication
  • Pathologically confirmed MCL, with documentation of monoclonal B cells showing one of the following:

    • Overexpression of cyclin D1 in association with other relevant markers (e.g., CD19, CD20, PAX5, CD5), OR
    • Chromosomal translocation t(11;14)(q13; q32), as assessed by cytogenetics, fluorescent in situ hybridization (FISH), or polymerase chain reaction (PCR)
  • Documented failure to achieve at least partial response (PR) with, or documented disease progression after the most recent treatment regimen
  • At least 1 prior treatment regimen for MCL which either included chemo-immunotherapy or a targeted agent (i.e., ibrutinib) administered for at least 2 cycles
  • Have radiologically measurable lymphadenopathy or extranodal lesion, (defined as >= 1 lesion that measures >= 2.0 cm in the longest diameter), or splenomegaly, or bone marrow involvement with or without malignant lymphocytosis
  • Absolute neutrophil count (ANC) >= 1,000/mm^3 without bone marrow involvement or ANC >= 500/mm^3 with bone marrow involvement (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  • Platelets >= 50,000/mm^3 without bone marrow involvement or platelets >= 30,000/mm^3 with bone marrow involvement (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)

    • NOTE: Platelet transfusions are not permitted within 7 days of platelet assessment
  • Total bilirubin =< 2 x upper limit of normal (ULN) (unless has Gilbert's disease or documented liver/biliary involvement by the lymphoma) (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  • Aspartate aminotransferase (AST) =< 2.5 x ULN (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  • Alanine aminotransferase (ALT) =< 2.5 x ULN (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  • Creatinine clearance of >= 30 mL/min per 24 hour urine test or the Cockcroft-Gault formula (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  • If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x ULN (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  • If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  • If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) =< 1.5 x ULN (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  • If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  • Left ventricular ejection fraction (LVEF) >= 45% (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)

    • Note: To be performed within 28 days prior to day 1 of protocol therapy
  • Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative) (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)

    • If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed
  • Meets other institutional and federal requirements for infectious disease titer requirements (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)

    • Note Infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy
  • Lipase =< 1.5 ULN (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  • Glycosylated hemoglobin (HbA1c) =< 8.5% (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  • Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)

    • If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 30 days after the last dose of protocol therapy

    • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only) without an alternative medical cause.

Exclusion Criteria:

  • Concurrent enrollment in another therapeutic investigational study
  • Prior treatment with venetoclax (or other investigational small molecule BCL2 inhibitors) or with copanlisib
  • Prior allogeneic stem cell transplant
  • Prior therapeutic intervention with any of the following:

    • Therapeutic anticancer antibodies within 2 weeks
    • Radio- or toxin-immunoconjugates within 10 weeks
    • All other chemotherapy, radiation therapy within 30 days prior to initiation of therapy
    • Targeted therapy within 6 half-lives
  • Vaccinated with live vaccines within 4 weeks of the first dose of study drug
  • Systemic continuous corticosteroid therapy at a daily dose higher than 20 mg prednisone or equivalent is not allowed. Participants may be using topical or inhaled corticosteroids
  • Concurrent administration of medications or food that are strong inhibitors or inducers of CYP3A4 taken within 7 days of starting study treatment
  • Current evidence of central nervous system involvement by the lymphoma
  • Uncontrolled active systemic infection
  • Unresolved toxicities (except alopecia) from prior anticancer therapy (including radiation) that have not resolved to grade =< 1 (per Common Terminology Criteria for Adverse Events [CTCAE] version [v] 5.0), or to the levels dictated in this protocol
  • Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection

    • Participants who are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded
  • History of prior malignancy except:

    • Malignancy treated with curative intent and no known active disease present for >= 2 years prior to initiation of therapy on current study
    • Adequately treated non-melanoma skin cancer or lentigo maligna (melanoma in situ) without evidence of disease
    • Adequately treated in situ carcinomas (e.g., breast, cervical, esophageal, etc.) without evidence of disease
    • Asymptomatic prostate cancer managed with "watch and wait" strategy or hormonal therapy
  • Major surgery within 4 weeks of the first dose of study drug
  • Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months of screening
  • Uncontrolled arterial hypertension despite optimal medical management
  • History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function, such as patients requiring oxygen supplementation
  • Uncontrolled diabetes mellitus despite optimal medical management (per investigator's opinion)
  • Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks) within 3 months before the start of study medication
  • Known hypersensitivity to any of the test drugs, test drug classes, or excipients in the formulation
  • Females only: Pregnant or breastfeeding
  • Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Sites / Locations

  • City of Hope Medical CenterRecruiting
  • Yale University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (copanlisib hydrochloride, venetoclax)

Arm Description

Patients receive copanlisib hydrochloride IV over 1 hour on days 1, 8, and 15, and venetoclax PO QD on days 1-28. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. Copanlisib will be given at 30mg, 45mg, or 60 mg depending on the assigned dose level. Venetoclax will have a weekly dose ramp up from 20mg, 50mg, 100mg, 200mg, and then 400mg thereafter.

Outcomes

Primary Outcome Measures

Incidence of dose limiting toxicities (Phase I)
Toxicities will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Overall response rate (Phase II)
Defined as the proportion of response-evaluable participants that achieve a best response of either complete response (CR) or partial response (PR) during protocol therapy. Will be estimated along with the 2-sided 95% exact binomial confidence interval.

Secondary Outcome Measures

Duration of response
Will be estimated using the Kaplan-Meier product-limit method along with the Greenwood estimator of standard error; 95% confidence interval for the survival timepoint estimates will be constructed based on the log-log transformation. Median survival time will be estimated when available.
Progression-free survival
Will be estimated using the Kaplan-Meier product-limit method along with the Greenwood estimator of standard error; 95% confidence interval for the survival timepoint estimates will be constructed based on the log-log transformation. Median survival time will be estimated when available.
Overall survival
Will be estimated using the Kaplan-Meier product-limit method along with the Greenwood estimator of standard error; 95% confidence interval for the survival timepoint estimates will be constructed based on the log-log transformation. Median survival time will be estimated when available.
Incidence of adverse events
Toxicity and adverse events will be recorded using the NCI CTCAE 5.0 scale. Safety and tolerability of copanlisib in conjunction with venetoclax will be summarized for all patients (evaluable for toxicity) combined and by dose level (if patients were treated at both dose level [DL]1 and DL-1). Adverse events will be tabulated and summarized by major organ category, grade, and drug attribution. Severe adverse event specific incidence and exact 95% confidence interval will be provided where necessary/appropriate.
Plasma pharmacokinetics (PK) of copanlisib (Cmax)
Maximum plasma concentration (Cmax).
Plasma pharmacokinetics (PK) of copanlisib (AUC)
Area under the Curve (AUC).

Full Information

First Posted
May 18, 2021
Last Updated
August 7, 2023
Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT04939272
Brief Title
Copanlisib and Venetoclax for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma
Official Title
A Phase 1/2 Study of Copanlisib and Venetoclax in Patients With Relapsed or Refractory Mantle Cell Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 29, 2022 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase I/II trial studies the side effects, best dose, and effectiveness of copanlisib and venetoclax in treating patients with mantle cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Copanlisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving copanlisib and venetoclax may help treat patients with mantle cell lymphoma.
Detailed Description
PRIMARY OBJECTIVES: I. To assess the safety, tolerability, and the maximum tolerated dose (MTD) of copanlisib hydrochloride (copanlisib) and venetoclax in patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL). (Phase 1) II. To estimate the efficacy (as measured by overall rate of response [ORR]) of copanlisib in combination with venetoclax in patients with R/R MCL. (Phase 2) SECONDARY OBJECTIVES: I. To characterize the safety profile of copanlisib in combination with venetoclax in patients with R/R MCL. (Phase 2) II. To evaluate duration of response (DOR) and progression-free survival (PFS) associated with combined administration of copanlisib/venetoclax. (Phase 2) III. To evaluate an overall survival (OS) associated with combined administration of copanlisib/venetoclax. (Phase 2) IV. To characterize the pharmacokinetics (PK) profile of copanlisib and venetoclax. (Phase 2) EXPLORATORY OBJECTIVES: I. Evaluate the emergence of resistant clones, as determined by the presence of novel mutations and expression of BCL2 family proteins. II. Characterize the T-cell population balance in patients treated with copanlisib/venetoclax. OUTLINE: This is a phase I, dose-escalation study of copanlisib hydrochloride, followed by a phase II study. Patients receive copanlisib hydrochloride intravenously (IV) over 1 hour on days 1, 8, and 15, and venetoclax orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Mantle Cell Lymphoma, Refractory Mantle Cell Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (copanlisib hydrochloride, venetoclax)
Arm Type
Experimental
Arm Description
Patients receive copanlisib hydrochloride IV over 1 hour on days 1, 8, and 15, and venetoclax PO QD on days 1-28. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. Copanlisib will be given at 30mg, 45mg, or 60 mg depending on the assigned dose level. Venetoclax will have a weekly dose ramp up from 20mg, 50mg, 100mg, 200mg, and then 400mg thereafter.
Intervention Type
Drug
Intervention Name(s)
Copanlisib Hydrochloride
Other Intervention Name(s)
5-Pyrimidinecarboxamide, 2-Amino-N-(2,3-dihydro-7-methoxy-8-(3-(4-morpholinyl)propoxy)imidazo(1,2-C)quinazolin-5-yl)-, Hydrochloride (1:2), Aliqopa, BAY 80-6946 Dihydrochloride, BAY-80-6946 Dihydrochloride, Copanlisib Dihydrochloride
Intervention Description
Patients receive copanlisib hydrochloride IV over 1 hour on days 1, 8, and 15 for each cycle. Copanlisib will be given at 30mg, 45mg, or 60 mg depending on the assigned dose level.
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Other Intervention Name(s)
ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto
Intervention Description
Patients receive venetoclax PO QD on days 1-28 for each cycle. Venetoclax will have a weekly dose ramp up in cycle one from 20mg, 50mg, 100mg, 200mg, and then 400mg daily thereafter starting from cycle 2.
Primary Outcome Measure Information:
Title
Incidence of dose limiting toxicities (Phase I)
Description
Toxicities will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Time Frame
Up to end of cycle 2 (1 cycle = 28 days)
Title
Overall response rate (Phase II)
Description
Defined as the proportion of response-evaluable participants that achieve a best response of either complete response (CR) or partial response (PR) during protocol therapy. Will be estimated along with the 2-sided 95% exact binomial confidence interval.
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Duration of response
Description
Will be estimated using the Kaplan-Meier product-limit method along with the Greenwood estimator of standard error; 95% confidence interval for the survival timepoint estimates will be constructed based on the log-log transformation. Median survival time will be estimated when available.
Time Frame
Time from the first achievement of PR or CR to time of progressive disease, start of non-protocol anti-lymphoma therapy, or death, whichever earlier, assessed up to 2 years
Title
Progression-free survival
Description
Will be estimated using the Kaplan-Meier product-limit method along with the Greenwood estimator of standard error; 95% confidence interval for the survival timepoint estimates will be constructed based on the log-log transformation. Median survival time will be estimated when available.
Time Frame
From start of protocol treatment to time of disease relapse/progression, or death due to any cause, whichever occurs earlier, assessed up to 2 years
Title
Overall survival
Description
Will be estimated using the Kaplan-Meier product-limit method along with the Greenwood estimator of standard error; 95% confidence interval for the survival timepoint estimates will be constructed based on the log-log transformation. Median survival time will be estimated when available.
Time Frame
From start of protocol treatment to time of death due to any cause, assessed up to 2 years
Title
Incidence of adverse events
Description
Toxicity and adverse events will be recorded using the NCI CTCAE 5.0 scale. Safety and tolerability of copanlisib in conjunction with venetoclax will be summarized for all patients (evaluable for toxicity) combined and by dose level (if patients were treated at both dose level [DL]1 and DL-1). Adverse events will be tabulated and summarized by major organ category, grade, and drug attribution. Severe adverse event specific incidence and exact 95% confidence interval will be provided where necessary/appropriate.
Time Frame
Up to 90 days after completion of treatment
Title
Plasma pharmacokinetics (PK) of copanlisib (Cmax)
Description
Maximum plasma concentration (Cmax).
Time Frame
From 30 minute before Copanlisib on cycle 2 day 15 through 24 hours after (Each cycle is 28 days)
Title
Plasma pharmacokinetics (PK) of copanlisib (AUC)
Description
Area under the Curve (AUC).
Time Frame
From 30 minute before Copanlisib on cycle 2 day 15 through 24 hours after.(Each cycle is 28 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Documented informed consent of the participant and/or legally authorized representative Assent, when appropriate, will be obtained per institutional guidelines Agreement to allow the use of archival tissue from diagnostic tumor biopsies If unavailable, exceptions may be granted with study principal investigator (PI) approval Age: >= 18 years Eastern Cooperative Oncology Group (ECOG) =< 2 Life expectancy >= 3 months (per physician assessment) Ability to take oral medication Pathologically confirmed MCL, with documentation of monoclonal B cells showing one of the following: Overexpression of cyclin D1 in association with other relevant markers (e.g., CD19, CD20, PAX5, CD5), OR Chromosomal translocation t(11;14)(q13; q32), as assessed by cytogenetics, fluorescent in situ hybridization (FISH), or polymerase chain reaction (PCR) Documented failure to achieve at least partial response (PR) with, or documented disease progression after the most recent treatment regimen At least 1 prior treatment regimen for MCL which either included chemo-immunotherapy or a targeted agent (i.e., ibrutinib) administered for at least 2 cycles Have radiologically measurable lymphadenopathy or extranodal lesion, (defined as >= 1 lesion that measures >= 2.0 cm in the longest diameter), or splenomegaly, or bone marrow involvement with or without malignant lymphocytosis Absolute neutrophil count (ANC) >= 1,000/mm^3 without bone marrow involvement or ANC >= 500/mm^3 with bone marrow involvement (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated) Platelets >= 50,000/mm^3 without bone marrow involvement or platelets >= 30,000/mm^3 with bone marrow involvement (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated) NOTE: Platelet transfusions are not permitted within 7 days of platelet assessment Total bilirubin =< 2 x upper limit of normal (ULN) (unless has Gilbert's disease or documented liver/biliary involvement by the lymphoma) (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated) Aspartate aminotransferase (AST) =< 2.5 x ULN (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated) Alanine aminotransferase (ALT) =< 2.5 x ULN (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated) Creatinine clearance of >= 30 mL/min per 24 hour urine test or the Cockcroft-Gault formula (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated) If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x ULN (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated) If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated) If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) =< 1.5 x ULN (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated) If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated) Left ventricular ejection fraction (LVEF) >= 45% (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated) Note: To be performed within 28 days prior to day 1 of protocol therapy Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative) (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated) If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed Meets other institutional and federal requirements for infectious disease titer requirements (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated) Note Infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy Lipase =< 1.5 ULN (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated) Glycosylated hemoglobin (HbA1c) =< 8.5% (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated) Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated) If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 30 days after the last dose of protocol therapy Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only) without an alternative medical cause. Exclusion Criteria: Concurrent enrollment in another therapeutic investigational study Prior treatment with venetoclax (or other investigational small molecule BCL2 inhibitors) or with copanlisib Prior allogeneic stem cell transplant Prior therapeutic intervention with any of the following: Therapeutic anticancer antibodies within 2 weeks Radio- or toxin-immunoconjugates within 10 weeks All other chemotherapy, radiation therapy within 30 days prior to initiation of therapy Targeted therapy within 6 half-lives Vaccinated with live vaccines within 4 weeks of the first dose of study drug Systemic continuous corticosteroid therapy at a daily dose higher than 20 mg prednisone or equivalent is not allowed. Participants may be using topical or inhaled corticosteroids Concurrent administration of medications or food that are strong inhibitors or inducers of CYP3A4 taken within 7 days of starting study treatment Current evidence of central nervous system involvement by the lymphoma Uncontrolled active systemic infection Unresolved toxicities (except alopecia) from prior anticancer therapy (including radiation) that have not resolved to grade =< 1 (per Common Terminology Criteria for Adverse Events [CTCAE] version [v] 5.0), or to the levels dictated in this protocol Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection Participants who are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded History of prior malignancy except: Malignancy treated with curative intent and no known active disease present for >= 2 years prior to initiation of therapy on current study Adequately treated non-melanoma skin cancer or lentigo maligna (melanoma in situ) without evidence of disease Adequately treated in situ carcinomas (e.g., breast, cervical, esophageal, etc.) without evidence of disease Asymptomatic prostate cancer managed with "watch and wait" strategy or hormonal therapy Major surgery within 4 weeks of the first dose of study drug Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months of screening Uncontrolled arterial hypertension despite optimal medical management History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function, such as patients requiring oxygen supplementation Uncontrolled diabetes mellitus despite optimal medical management (per investigator's opinion) Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks) within 3 months before the start of study medication Known hypersensitivity to any of the test drugs, test drug classes, or excipients in the formulation Females only: Pregnant or breastfeeding Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alexey Danilov
Organizational Affiliation
City of Hope Medical Cneter
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexey V. Danilov
Phone
626-218-2405
Email
adanilov@coh.org
First Name & Middle Initial & Last Name & Degree
Alexey V. Danilov
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shalin Kothari
Phone
203-737-3509
Email
shalin.kothari@yale.edu
First Name & Middle Initial & Last Name & Degree
Shalin Kothari

12. IPD Sharing Statement

Learn more about this trial

Copanlisib and Venetoclax for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma

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