Venetoclax With Obinutuzumab and Magrolimab (VENOM) in Relapsed and Refractory Indolent B-cell Malignancies

Summary

Background:

B-cell lymphoma is a cancer of certain white blood cells (called lymphocytes). These cells are found in lymph nodes. The cancer can cause enlargement of the lymph nodes leading to pain and discomfort. Swollen lymph nodes can also press on nearby organs such as liver and kidneys which can affect normal functioning of the organs. Researchers think that a new combination of drugs may be able to help.

Objective:

To find out if it is safe to give the combination of Magrolimab, Obinutuzumab and Venetoclax to people with B-cell lymphomas.

Eligibility:

Adults age 18 and older with an indolent B-cell lymphoma whose disease has returned or progressed after other treatment. Indolent B-cell lymphoma for this protocol is defined as having either follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma or marginal zone lymphoma.

Design:

Participants will be screened under a separate protocol.

Participants will have 28-day 'cycles' of treatment. They will take Venetoclax by mouth daily. They will get Obinutuzumab and Magrolimab by intravenous (IV) infusion. Treatment will last for about 8 months. They may be able to have more cycles of treatment if their cancer is responding well.

Participants will have physical exams, medical histories, and medicine reviews. Data about how they function in their daily activities will be obtained. They will have blood and urine tests. They may have bone marrow tests.

Participants will have imaging scans. These will include computed tomography (CT) and/or magnetic resonance imaging (MRI) scans and positron emission tomography (PET) scans.

Participants may give a cheek swab or saliva sample. They may give tumor tissue and bone marrow samples. These samples may be used for gene testing.

Participants will have a follow-up visit about 30 days after treatment ends. Then they will have visits every 3 months for the first 2 years, every 6 months for the next 3 years, and then yearly after that.

Conditions

• Follicular Lymphoma
• Marginal Zone Lymphoma
• Mantle Cell Lymphoma
• Chronic Lymphocytic Lymphoma
• B-Cell Lymphoma

Interventions

DRUG

Obinutuzumab

Administered intravenously, on Days 1, 2, 8 and 15 of Cycle 1 at doses escalating from 100mg - 1000mg then on the first day for all subsequent cycles at 1000mg for dose finding phase. For expansion phase, administered on Days 1, 2, 8 and 15 of Cycle 2 at doses escalating from 100mg - 1000mg then on the first day for all subsequent cycles at 1000mg.

DRUG

Venetoclax

For follicular lymphoma (FL) patients in dose finding phase, administered orally at a dose of 600mg or 800mg depending on tolerance, daily, cycles 1-12. For MZL (Marginal Zone Lymphoma), MCL (Mantle Cell Lymphoma) or CLL (Chronic Lymphocytic Leukemia) patients in dose finding phase administered at an escalating dose from 20mg-400mg Cycle 1 on days 1-35, and at a dose of 400mg per day for Cycles 2-12. Patients in expansion phase will receive target dose established from dose finding cohorts daily for all 12 cycles.

DRUG

Magrolimab

Administered intravenously, starting at 1 mg/kg on second day of first cycle then 30mg/kg on days 8, 15 and 22 of cycle 1 and days 1 and 15 of cycles 2-12 for patients in both the dose finding and expansion phases.

DRUG

Acetaminophen

Premedication with 650mg acetaminophen 30-60 minutes prior to obinutuzumab doses.

DRUG

Diphenhydramine

Premedication with 25-50mg diphenhydramine 30-60 minutes prior to obinutuzumab doses.

DRUG

Prednisone/prednisolone

Premedication with 100mg intravenous prednisone/prednisolone 30-60 minutes before obinutuzumab infusion.

DRUG

Methylprednisolone

Premedication with intravenous methylprednisolone 80mg 30-60 minutes before obinutuzumab infusion.

DIAGNOSTIC_TEST

CT Scan chest/abdomen/pelvis

Screening, baseline, window Cycle -1/pre cycle 1, cycles 6-12; cycles 3-9, end of treatment and follow-up.

DIAGNOSTIC_TEST

MRI

Screening, baseline, window Cycle -1/pre cycle 1, cycles 6-12; cycles 3-9, end of treatment and follow-up.

DIAGNOSTIC_TEST

18-FDG-PET

Baseline, Cycle -1, Day 1, window Cycle -1/pre cycle 1, cycles 6-12, end of treatment and follow-up.

PROCEDURE

Bone Marrow Biopsy

Screening, Cycle 7-12, Day 1 and end of treatment.

PROCEDURE

Bone Marrow Aspiration

Screening, Cycle 7-12, Day 1 and end of treatment.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Mark J Roschewski, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-12-16

Primary Completion

2024-03-29

Completion

2024-06-20

FDA Drug

Yes

Countries

• United States

Study Locations