Copanlisib and Combination Chemotherapy for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma or Relapsed Grade 3b Follicular Lymphoma

NCT04156828 | Terminated Phase 1 DMC FDA Drug

• 3 other identifiers: RG1005097NCI-2019-0728610332
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the best dose of copanlisib when given together with combination chemotherapy (R-GCD) in treating patients with diffuse large B-cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory) or grade 3b follicular lymphoma that has come back (relapsed) after 1 prior line of therapy. Copanlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Rituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as gemcitabine, carboplatin, and dexamethasone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving copanlisib together with R-GCD as second line therapy may improve the complete response rate for patients with diffuse large B-cell lymphoma or follicular lymphoma.

Conditions

Grade 3b Follicular Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Non-Hodgkin's Lymphoma

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity (DLT)

  Will assess the presence of a DLT in the first cycle of treatment The dose that estimate of the maximum tolerated dose (MTD) will be obtained using the continuous reassessment method (CRM). Moreover, the proportion of DLT at each dose level will be reported along with the final estimates of the probability of DLT at the MTD based on the CRM along with the 95% confidence interval.

  Up to 21 days

Secondary Outcomes (8)

• Complete response rate

  Up to 1 year after 3 cycles of treatment (each cycle is 21 days)

• Objective response rate

  Up to 1 year after 3 cycles of treatment (each cycle is 21 days)

• Ability to mobilize an adequate number of CD34+ stem cells for autologous stem cell transplant (ASCT)

  Up to 1 year post treatment

• Ability to proceed with ASCT

  Up to 1 year post treatment

• Progression free survival (PFS)

  At 1 year

Study Arms (1)

Treatment (copanlisib, R-GCD)

EXPERIMENTAL

Patients receive copanlisib IV and gemcitabine IV on days 1 and 8, carboplatin IV and rituximab IV on day 1, and dexamethasone PO or IV 30-60 minutes prior to chemotherapy on day 1 and PO in AM or 30-60 minutes prior to chemotherapy on days 2-4. Patients also receive pegfilgrastim SC on day 8 or 9. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Copanlisib; Drug: Gemcitabine; Drug: Carboplatin; Drug: Dexamethasone; Biological: Rituximab; Biological: Pegfilgrastim

Interventions

Copanlisib DRUG

Given IV

Also known as: 1032568-63-0, BAY 80-6946, PI3K Inhibitor BAY 80-6946

Treatment (copanlisib, R-GCD)

Gemcitabine DRUG

Given IV

Also known as: dFdCyd, Difluorodeoxycytidine, 1-(2-Oxo-4-amino-1

Treatment (copanlisib, R-GCD)

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Nealorin, Novoplatinum, Paraplatin, Paraplatine, Platinwas, Ribocarbo

Treatment (copanlisib, R-GCD)

Dexamethasone DRUG

Given PO

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin Depot, Auricularum, Auxiloson, Baycadron, Baycuten, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decalix, Decameth, Decasone, Deltafluorene, Desameton, Dexa-Mamallet, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Treatment (copanlisib, R-GCD)

Rituximab BIOLOGICAL

Given IV

Also known as: 174722-31-7, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, Rituxan, Rituximab ABBS, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, rituximab-abbs, RTXM83, Truxima

Treatment (copanlisib, R-GCD)

Pegfilgrastim BIOLOGICAL

Given SC

Also known as: 208265-92-3, Filgrastim SD-01, filgrastim-SD/01, Fulphila, HSP-130, Jinyouli, Neulasta, Pegfilgrastim Biosimilar HSP-130, Pegfilgrastim Biosimilar Pegcyte, Pegfilgrastim-jmdb, SD-01, SD-01 sustained duration G-CSF, Nyvepria, Pegfilgrastim Biosimilar Udenyca, Pegfilgrastim Biosimilar Ziextenzo, Udenyca, Ziextenzo

Treatment (copanlisib, R-GCD)

Eligibility Criteria

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

You may qualify if:

• Subjects must meet one of the following criteria:
• Histologically confirmed relapsed/refractory DLBCL or grade 3b follicular lymphoma.
• Follicular lymphoma that has relapsed within 2 years of primary therapy that included an anti-CD20 antibody in combination with chemotherapy as measured from the date of the last dose of chemotherapy
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Previous exposure to other PI3K inhibitors (except copanlisib) is acceptable provided there is no resistance (resistance defined as no response \[response defined as partial response (PR) or CR\] at any time during therapy), or progressive disease (PD) after any response (PR/CR) or after stable disease within 6 months from the end of the therapy with a PI3K inhibitor
• Willingness and ability to comply with study and follow-up procedures, and give written informed consent
• Female subjects of childbearing potential must be surgically sterile, be post-menopausal (per institutional guidelines), or must have a negative pregnancy test within 3 days prior to cycle 1 day 1 and agree to use medically acceptable contraception throughout the study period and for 4 months after the last dose of either study drug. Men of reproductive potential may not participate unless they agree to use medically acceptable contraception throughout the study period and for 4 months after the last dose of either study drug
• Patients must be expected to receive at least 2 cycles of therapy
• Patients should have an expected survival if untreated of \>= 90 days
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) (\< 3 x ULN for patients with Gilbert-Meulengracht syndrome or for patients with cholestasis due to compressive adenopathies of the hepatic hilum) (collected no more than 7 days before starting study treatment)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x ULN (=\< 5 x ULN for patients with liver involvement by lymphoma (collected no more than 7 days before starting study treatment)
• Lipase =\< 1.5 x ULN (collected no more than 7 days before starting study treatment)
• International normalized ratio (INR) =\< 1.5 and partial thromboplastin time (PTT) =\< 1.5 x ULN. PT can be used instead of INR if =\< 1.5 x ULN (collected no more than 7 days before starting study treatment)
• Platelet count \>= 75,000 /mm\^3. For patients with lymphomatous bone marrow infiltration, platelet count \>= 50,000 /mm\^3 (collected no more than 7 days before starting study treatment)
• Hemoglobin (Hb) \>= 8 g/dl (collected no more than 7 days before starting study treatment). Packed red blood cell transfusion or erythropoietin should not be given less than 7 days before the exam collection

You may not qualify if:

• More than one prior line of therapy for DLBCL
• More than one prior line of chemoimmunotherapy
• Prior treatment with copanlisib
• Documented evidence of resistance to prior treatment with idelalisib or other PI3K inhibitors defined as: No response (response defined as partial response \[PR\] or complete response \[CR\]) at any time during therapy, or Progression (PD) after any response (PR/CR) or after stable disease within 6 months from the end of the therapy with a PI3K inhibitor
• Prior treatment including systemic therapy or radiotherapy within 21 days of study initiation
• Poorly controlled diabetes mellitus defined as hemoglobin A1c \> 8.5%
• Known lymphomatous involvement of the central nervous system
• Known history of human immunodeficiency virus (HIV) infection. All patients must be screened for HIV up to 28 days prior to study drug start using a blood test for HIV according to local regulations
• Hepatitis B (HBV) or C (HCV) infection. All patients must be screened for HBV and HCV up to 28 days prior to study drug start using the routine hepatitis virus laboratorial panel. Patients positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) will be eligible if they are negative for HBV-deoxyribonucleic acid (DNA), these patients should receive prophylactic antiviral therapy. Patients positive for anti-HCV antibody will be eligible if they are negative for HCV-ribonucleic acid (RNA)
• Previous or concurrent history of malignancies within 3 years prior to study. Any exceptions beyond those listed below must be approved by the principal investigator:
• Cervical carcinoma in situ
• Non-melanoma skin cancer
• Superficial bladder cancer (Ta \[non-invasive tumor\], Tis \[carcinoma in situ\] and T1 \[tumor invades lamina propria\])
• Localized prostate cancer
• Active, clinically serious infections (\> Common Terminology Criteria for Adverse Events \[CTCAE\] grade 2)

Sponsors & Collaborators

• University of Washington: lead
• Bayer: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Non-Hodgkin

Interventions

copanlisib; Gemcitabine; Carboplatin; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; Rituximab; CT-P10; pegfilgrastim

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ryan Lynch

  Fred Hutch/University of Washington Cancer Consortium

  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: SPONSOR

Study Record Dates

• First Submitted: November 4, 2019
• First Posted: November 8, 2019
• Study Start: March 31, 2020
• Primary Completion: April 27, 2022
• Study Completion: June 8, 2023
• Last Updated: June 29, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)