- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04431635
Dose De-escalation Study of the PI3k Alpha/Delta Inhibitor, Copanlisib Given in Combination With the Immunotherapeutic Agents, Nivolumab and Rituximab in Patients With Relapsed/Refractory Indolent Lymphoma
Phase IB Dose De-escalation Study of the PI3k Alpha/Delta Inhibitor, Copanlisib Given in Combination With the Immunotherapeutic Agents, Nivolumab and Rituximab in Patients With Relapsed/Refractory Indolent Lymphoma.Big Ten Cancer Research Consortium BTCRC-LYM17-145
Patients with relapsed or refractory follicular or marginal zone lymphoma who have received at least one prior line of therapy will receive
- Copanlisib IV: day 1, 8, 15 every 28 days
- Nivolumab IV: Cycle 1 days 1 and 15; then day 1 only
- Rituximab IV: Cycle 1 days 1, 8, 15, 22; then day 1 (C2-6); then Q2 cycles (8-12)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Yasmin H Karimi, MD
- Phone Number: 734-764-8195
- Email: karimiy@med.umich.edu
Study Contact Backup
- Name: Milena Petkov
- Phone Number: 40 317-634-5842
- Email: mpetkov@hoosiercancer.org
Study Locations
-
-
Illinois
-
Chicago, Illinois, United States, 60612
- University of Illinois Cancer Center
-
-
Michigan
-
Ann Arbor, Michigan, United States, 48109
- University of Michigan Comprehensive Cancer Center
-
Ann Arbor, Michigan, United States, 48109
- University of Michigan Health System
-
-
Nebraska
-
Omaha, Nebraska, United States, 68198
- University of Nebraska Medical Center
-
-
New Jersey
-
New Brunswick, New Jersey, United States, 08903
- Rutgers Cancer Institute of New Jersey
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Age ≥18 years at the time of informed consent.
Diagnosis of relapsed or refractory indolent follicular or marginal zone lymphoma established by histologic assessment by a hematopathologist that has relapsed after at least one line of chemo-immunotherapy.
- Immunohistochemistry of the biopsy or
- Flow cytometry of the biopsy
- ECOG Performance Status ≤ 2
- Has an indication for treatment based on the presence of symptoms and/or GELF criteria as referenced in appendix A.
- Must have failed or not be a candidate for an autologous stem cell transplantation.
Women of childbearing potential must be willing to use appropriate contraception (barrier and hormonal therapy) or abstain from heterosexual activity from the point of registration through at least 12 months after the last dose of study drugs.
-- NOTE: Women of childbearing potential are those who have not been surgically sterilized, have not been free of menses for ≥ 1 year, or her sole male partner has had a vasectomy at least 6 months prior to screening.
- Male subjects capable of fathering a child who have a female partner of childbearing potential must agree to use appropriate method(s) of contraception or abstain from heterosexual activity starting with the first dose of study drug through 1 month after the last dose of the study drugs.
Adequate organ function defined as
Hepatic:
- Total Bilirubin ≤ 1.5 mg/dL
- AST and ALT ≤ 2.5 x ULN.
- Renal: Creatinine < 2.0 mg/dl or CrCL > 30 mL/minute
Bone marrow function:
- ANC ≥ 1000/mm3 (500/mm3 if known bone marrow (BM) involvement)
- Platelet ≥ 75,000/mm3 (or 50,000/mm3 if known BM involvement)
- Hgb > 9 g/dL (transfusions allowed to meet this criterion)
- Adequate glycemic control as demonstrated by a baseline fasting blood sugar (BS) ≤ 150 mg/dL. If uncontrolled then patient must be referred to PCP or endocrinology for medical management. Patient may be enrolled if adequate control is obtained prior to day 1 of therapy.
- Adequate blood pressure (BP) control as demonstrated by a baseline BP of < 150/90. If uncontrolled then patient must be referred to PCP for medical management. Patient may be enrolled if adequate control is obtained prior to day 1 of therapy.
Prior treatment is allowed if
- at least 4 weeks must have elapsed since last chemotherapy and/or radiation and the patient has recovered to ≤ grade 1 toxicity from all treatment related events.
- at least 3 months must have passed since radio-immunotherapy.
- at least 3 months have passed since date of stem cell infusion (autograft) and patient has recovered to ≤ grade 1 toxicities related to this procedure.
- Prior treatment with a PD-1/PD-L1 and/or PI3K inhibitor is allowed unless patient prior treatment was discontinued for intolerance.
Exclusion Criteria:
- Pregnant or breastfeeding women. NOTE: Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to study registration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. NOTE: Breast milk cannot be stored for future use while the mother is being treated on study.
- Diagnosis of follicular grade 3b, post-transplant lymphoproliferative disorder (PTLD), or presence of histologic transformation.
- Subjects with LFT abnormalities at baseline (above values per inclusion criteria), history of cirrhotic liver morphology or alcoholic cirrhosis, subjects who use acetaminophen at doses in excess of 2 g every day and have evidence of compromised hepatic reserve.
- Primary or metastatic CNS disease prior to study enrollment
- Uncontrolled current illness, including, but not limited to ongoing or active infections, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmia, evidence of interstitial lung disease or active, noninfectious pneumonitis including symptomatic and/or pneumonitis requiring treatment and/or psychiatric illness or social situations that would limit compliance with study requirements.
- History of inflammatory bowel disease i.e. Crohn's disease, ulcerative colitis.
- HIV infection. NOTE: HIV testing is required.
- Active infection with Hepatitis B or C virus (defined as a positive Hepatitis B surface antigen/ positive Hepatitis C antibody or detectable viral load by PCR). Patients with positive antibody but negative viral loads will be eligible for study participation but will require appropriate prophylaxis.
NOTE: Hepatitis B and C testing are required.
- Screening rate-corrected (using Friderica's correction) QT interval (QTcF) must not be > 480 msec via a standard 12-lead ECG within 28 days prior to registration.
- Concomitant therapy in the last 4 weeks of any of the following: cytotoxic chemotherapy, immunosuppressive agents, other investigational therapies, or chronic use of systemic corticosteroids (doses ≤ 10 mg/day prednisone or equivalent are permitted).
Active or prior documented autoimmune or inflammatory disorders within the past 3 years prior to study registration. The following are exceptions to this criterion:
- Subjects with vitiligo or alopecia
- Subjects with hypothyroidism (eg. following Hashimoto syndrome) stable on hormone replacement or psoriasis not requiring systemic treatment.
- Known allergy or reaction to any component of either study drug formulation.
- Prior allogeneic stem cell transplant.
- Receipt of live attenuated vaccine within 30 days before the first dose of study treatment.
- HbA1c > 8.5% at Screening
- Patient that require treatment with agents that are CYP3A4 inhibitors or strong CYP3A4 inducers. Patients who are on agents that fall into this category must be off for at least two weeks prior to start of treatment.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm A: Copanlisib, Nivolumab & Rituximab
Copanlisib IV: day 1, 8, 15 every 28 days Nivolumab IV: Cycle 1 days 1 and 15; then day 1 only Rituximab IV: Cycle 1 days 1, 8, 15, 22; then day 1 (C2-6); then Q2 cycles (8-12)
|
Copanlisib IV: day 1, 8, 15 every 28 days
Nivolumab IV: Cycle 1 days 1 and 15; then day 1 only
Rituximab IV: Cycle 1 days 1, 8, 15, 22; then day 1 (C2-6); then Q2 cycles (8-12)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
MTD (Maximum Tolerated Dose) of copanlisib given in combination with nivolumab and rituximab
Time Frame: 28 days
|
To estimate the MTD (Maximum Tolerated Dose) of copanlisib given in combination with nivolumab and rituximab
|
28 days
|
Complete Response rate of the combination of copanlisib, nivolumab, and rituximab given at the MTD.
Time Frame: 1 year
|
To estimate the Complete Response (CR) rate of the combination of copanlisib, nivolumab, and rituximab given at the MTD as determined by Lyric criteria [Cheson 2016}
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Summarize Adverse Events
Time Frame: Up to two years
|
Summarize all adverse events graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
|
Up to two years
|
Overall Response
Time Frame: 1 year
|
The rate of overall response, defined as either CR or PR within 1 year of initiation of therapy.
|
1 year
|
Duration of Response
Time Frame: Up to two years
|
3. Duration of response, as calculated from the time of initial response (CR or PR, determined by Lyric criteria [Cheson 2016]) until disease progression or death due to any cause (whichever occurs first).
|
Up to two years
|
Progression Free Survival
Time Frame: Up to two years
|
4. Progression free survival, as calculated from the first dose of the combination to the occurrence of definitive disease progression (as defined by Cheson 2016) or death from any cause, whichever comes first.
|
Up to two years
|
Time to Next Treatment
Time Frame: Up to two years
|
Time to next treatment (TTNT) is defined as the time from end of primary treatment to institution of next therapy.
|
Up to two years
|
Collaborators and Investigators
Investigators
- Principal Investigator: Yasmin H Karimi, MD, The University of Michigan Rogel Cancer Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Nivolumab
- Rituximab
Other Study ID Numbers
- UMCC 2019.097
- BTCRC-LYM17-145 (Other Identifier: BTCRC)
- HUM00166647 (Other Identifier: University of Michigan)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Indolent Lymphoma
-
Fondazione Italiana Linfomi - ETSActive, not recruitingIndolent B-Cell LymphomasFrance, Italy, Brazil, Austria, Portugal, Ukraine
-
Ludwig-Maximilians - University of MunichHoffmann-La Roche; Janssen-Cilag G.m.b.HActive, not recruitingIndolent Non-Hodgkin LymphomaGermany
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedMantle Cell Lymphoma | Recurrent Diffuse Large B-Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | Refractory Indolent Adult Non-Hodgkin Lymphoma | Recurrent Follicular Lymphoma | Refractory Follicular Lymphoma | Recurrent Indolent Adult Non-Hodgkin LymphomaUnited States
-
SecuraBioCompletedIndolent Non-Hodgkin LymphomaKorea, Republic of, Czechia, United States, United Kingdom, Italy, Poland, Russian Federation, Germany
-
S*BIOCompletedHodgkin Lymphoma | Mantle Cell Lymphoma | Indolent LymphomaUnited States, Canada
-
PrECOG, LLC.Genentech, Inc.TerminatedIndolent Non-Hodgkin's LymphomaUnited States
-
Gruppo Italiano Studio LinfomiUnknown
-
Shanghai YingLi Pharmaceutical Co. Ltd.Not yet recruitingIndolent B-cell Lymphoma
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingAnn Arbor Stage I Grade 1 Follicular Lymphoma | Ann Arbor Stage I Grade 2 Follicular Lymphoma | Ann Arbor Stage II Grade 1 Follicular Lymphoma | Ann Arbor Stage II Grade 2 Follicular Lymphoma | Ann Arbor Stage IV B-Cell Non-Hodgkin Lymphoma | Ann Arbor Stage I B-Cell Non-Hodgkin Lymphoma | Ann... and other conditionsUnited States
-
Massachusetts General HospitalDana-Farber Cancer Institute; Genentech, Inc.; Brigham and Women's HospitalCompletedB-cell Lymphoma | Indolent B-cell LymphomaUnited States
Clinical Trials on Copanlisib
-
Dorothy Sipkins, MD, PhDBayerTerminatedLeukemia, Acute LymphocyticUnited States
-
Memorial Sloan Kettering Cancer CenterBayerCompletedMantle Cell Lymphoma (MCL)United States
-
Memorial Sloan Kettering Cancer CenterActive, not recruitingRefractory/Recurrent Primary Central Nervous System Lymphoma (PCNSL)United States
-
BayerTerminatedOsteosarcoma | Ewing Sarcoma | Neuroblastoma | Rhabdomyosarcoma | Relapsed or Refractory Solid Tumors or Lymphoma in ChildrenUnited States
-
BayerCompleted
-
BayerCompleted
-
BayerActive, not recruitingRelapsed or Refractory Indolent Non-Hodgkin LymphomaTaiwan
-
BayerNo longer availableCancerBrazil, Hong Kong, Hungary, Malaysia, Poland, Romania, Russian Federation, Taiwan, Ukraine, Ireland, Chile
-
BayerCompletedHepatic Insufficiency, Renal InsufficiencyGermany, Romania