Response-Adapted Therapy With Copanlisib and Rituximab in Untreated Follicular Lymphoma

Summary

Background:

The disease follicular lymphoma (FL) develops when the body makes abnormal B-cells. These cells usually build up in the lymph nodes, but can also affect other parts of the body. Researchers want to see if a combination of drugs can attack the cancer cells in people with FL.

Objective:

To see if copanlisib plus rituximab is effective at slowing the growth of FL.

Eligibility:

People with FL who have not had prior treatment for their disease

Design:

Participants will be screened with:

* Medical and cancer history
* Physical exam
* Review of symptoms and ability to perform daily activities
* Blood and urine tests
* Small amount of bone marrow removed by needle in the hip bone
* Scans of the chest, abdomen, and pelvis. Some scans will use a radioactive tracer.

Participants will get the study drugs in 28-day cycles for up to 13 cycles. Both are given as an intravenous (IV) infusion. Copanlisib is given over about 1 hour. Rituximab is given over several hours.

* For 1 cycle, they will get 3 weekly doses of copanlisib.
* For the next cycle, they will get 3 weekly doses of copanlisib and 4 weekly doses of rituximab.
* For all other cycles, they will get 2-3 weekly doses of copanlisib and 1 dose of rituximab.

Participants will repeat some screening tests during the cycles. They will give a cheek swab and/or saliva sample and may have a tumor sample taken.

After treatment, some participants will have a few follow-up visits each year for 5 years, then 1 each year. They will repeat screening tests.

Other participants will be contacted by phone every few months.

Conditions

• Follicular Lymphoma
• Non-Hodgkin's Lymphoma
• NHL

Interventions

BIOLOGICAL

Rituximab

Rituximab is administered at a dose of 375 mg/m\^2 via intravenous (IV) weekly for the first 4 weeks on Days 1, 8, 15, and 22 during cycle 1. With subsequent cycles (cycles 2-6), rituximab will be dosed only once on Day 1 of the cycle.

DRUG

Copanlisib

Copanlisib is administered at a fixed dose of 60 mg via intravenous (IV) weekly for the first 3 weeks on Days 1, 8, and 15 followed by a 1-week break (no infusion on Day 22)

PROCEDURE

Bone Marrow Aspiration/Biopsy

Screening. Cycles 6 \& 12, last 7 days of the cycle (disease evaluations). Follow-up (prior to progressive disease) every 3 or 6 months. Bone marrow aspiration with flow cytometry and biopsy (within 12 months prior to starting treatment) if clinically indicated; repeat in follow-up to confirm response or progression.

DIAGNOSTIC_TEST

CT Scans

Screening and Baseline. Copanlisib Window (Cycle 0/ore Cycle 1 Day 1) Day-28 to -1 (-14 scheduling window). Cycles 3 \& 9 and Cycles 6 \& 12, last 7 days of the cycle (disease evaluations). Follow-up (prior to progressive disease) every 3 or 6 months. End of treatment (discontinued/progressive disease). Follow-up (prior to progressive disease) every 3 or 6 months. CT scans (preferred) of chest, abdomen and pelvis at baseline; may be adjusted to assess additional known sites of disease, as needed. Scans performed after cycles 3 and 6 (last 7 days of each cycle) of both induction and maintenance, as applicable. Repeat also within last 7 days of copanlisib window. MRIs may be used instead of CT scans as necessary.

DIAGNOSTIC_TEST

18F-FDG-PET/CT Scan15

Screening and Baseline. Copanlisib Window (Cycle 0/ore Cycle 1 Day 1) Day-28 to -1 (-14 scheduling window). Cycles 6 \& 12, last 7 days of the cycle (disease evaluations). PET scans to be performed after cycles 6 and 12 (last 7 days of each cycle) of both induction and maintenance, as applicable. Repeat also within last 7 days of copanlisib window.

DIAGNOSTIC_TEST

Electrocardigram

Baseline. Copanlisib Window (Cycle 0/ore Cycle 1 Day 1) Day-28 to -1 (-14 scheduling window). Cycles 3 \& 9 and Cycles 6 \& 12, last 7 days of the cycle (disease evaluations). End of treatment (discontinued/progressive disease). Follow-up (prior to progressive disease) every 3 or 6 months. Participants with prolonged QTc at baseline, participants with congenital prolonged QT syndrome, and participants chronically on medications as specified in the protocol will have ECG monitoring after copanlisib window, and every 3 cycles thereafter.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Rahul Lakhotia, M.B.B.S. · National Cancer Institute (NCI)

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-08-22

Primary Completion

2025-09-24

Completion

2027-01-01

FDA Drug

Yes

Countries

• United States

Study Locations