Copanlisib and Nivolumab in Treating Participants With Richter's Transformation or Transformed Indolent Non-Hodgkin's Lymphoma
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|ClinicalTrials.gov Identifier: NCT03884998|
Recruitment Status : Recruiting
First Posted : March 21, 2019
Last Update Posted : December 2, 2019
|Condition or disease||Intervention/treatment||Phase|
|Chronic Lymphocytic Leukemia Richter Syndrome Diffuse Large B Cell Lymphoma Follicular Lymphoma Indolent Non-hodgkin Lymphoma Loss of Chromosome 17p Lymphoplasmacytic Lymphoma Marginal Zone Lymphoma TP53 Gene Mutation||Drug: Copanlisib Biological: Nivolumab||Phase 1|
I. To evaluate the maximum-tolerated dose (MTD) of copanlisib administered in combination with nivolumab in patients with transformed chronic lymphocytic leukemia (CLL)/non-Hodgkin's lymphoma (NHL).
I. To evaluate the preliminary efficacy of copanlisib administered in combination with nivolumab in patients with transformed CLL/NHL.
I. To evaluate the T-cell repertoire and activation patterns following dual targeting of PI3K and PD-1.
II. To establish if PD-1/PD-L 1 expression correlates with response to the combination of copanlisib and nivolumab.
OUTLINE: This is a dose-escalation study of copanlisib.
Participants receive copanlisib intravenously (IV) over 60 minutes on days 1, 8, and 15 and nivolumab IV over 30 minutes on days 1 and 15. Courses repeat every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, participants are followed up every 3 months for 1 year and then every 4-6 months thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of PI3Kα,δ Inhibitor Copanlisib in Combination With PD-1 Antagonist Nivolumab in Patients With Transformed Chronic Lymphocytic Leukemia (Richter's Transformation) or Non-Hodgkin Lymphoma|
|Actual Study Start Date :||March 18, 2019|
|Estimated Primary Completion Date :||January 6, 2021|
|Estimated Study Completion Date :||January 6, 2023|
Experimental: Treatment (copanlisib and nivolumab)
Participants receive copanlisib IV over 60 minutes on days 1, 8, and 15 and nivolumab IV over 30 minutes on days 1 and 15. Courses repeat every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
Other Name: 1032568-63-0, BAY
Other Name: 946414-94-4, BMS-936558, MDX-1106, NIVO, NIVOLUMAB, Nivolumab, ONO-4538, Opdivo
- Incidence of dose-limiting toxicities of copanlisib in combination with nivolumab [ Time Frame: Up to day 28 ]Will be summarized for the safety population by dose level. All adverse events (AEs) will be coded by system organ class, Medical Dictionary for Regulatory Activities (MedDRA) preferred term, and severity grade using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.
- Incidence of adverse events as assessed by CTCAE v5 [ Time Frame: Up to 48 weeks ]All adverse events will be tabulated and summarized by major organ category, grade, anticipation, and drug attribution. Serious adverse events (SAE) specific incidence and exact 95% confidence interval will be provided where appropriate.
- Overall response rate (ORR) or complete response (CR) + partial response (PR) [ Time Frame: Up to 48 weeks ]Will be summarized with 95% confidence intervals.
- Duration of response [ Time Frame: Up to 48 weeks ]Will be summarized descriptively using means and standard deviation along with 95% confidence interval.
- Progression-free survival (PFS) [ Time Frame: Date of first study treatment and the date of objective signs of disease progression, subsequent anti-leukemic therapy, or death, whichever is reported first, assessed up to 48 weeks ]Will be summarized descriptively using the Kaplan-Meier estimate along with 95% confidence interval. We will also perform subset analysis with subjects who were treated at the maximum tolerated dose (MTD).
- Overall survival [ Time Frame: Up to 48 weeks ]Will be summarized descriptively using the Kaplan-Meier estimate along with 95% confidence interval. We will also perform subset analysis with subjects who were treated at the MTD.
- Tumor response [ Time Frame: Up to 48 weeks ]Will explore the association between tumor PD-L1 expression.
- T cell repertoire after treatment [ Time Frame: Up to 48 weeks ]Evaluation of T-cell repertoire of patients with transformed chronic lymphocytic leukemia (CLL)/non-Hodgkin's lymphoma (NHL) after receiving nivolumab
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03884998
|Contact: Alexey Danilov, MDfirstname.lastname@example.org|
|Contact: Basak Gokcoraemail@example.com|
|United States, Massachusetts|
|Dana Farber Cancer Institute||Recruiting|
|Boston, Massachusetts, United States, 02284|
|Contact: Matthew Davids, MD, MMsc 617-632-5847|
|Principal Investigator: Matthew Davids, MD, MMsc|
|United States, Oregon|
|OHSU Knight Cancer Institute||Recruiting|
|Portland, Oregon, United States, 97239|
|Contact: Alexey V. Danilov 503-494-8426 firstname.lastname@example.org|
|Principal Investigator: Alexey V. Danilov|
|Principal Investigator:||Alexey Danilov, MD||OHSU Knight Cancer Institute|