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

Part of paid clinical trials in Bethesda, Maryland.

Sponsor
National Cancer Institute (NCI)
Study ID
NCT04599634
Phase
PHASE1
Status
Completed

Conditions

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

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Obinutuzumab — DRUG
    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.
  • Venetoclax — DRUG
    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.
  • Magrolimab — DRUG
    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.
  • Acetaminophen — DRUG
    Premedication with 650mg acetaminophen 30-60 minutes prior to obinutuzumab doses.
  • Diphenhydramine — DRUG
    Premedication with 25-50mg diphenhydramine 30-60 minutes prior to obinutuzumab doses.
  • Prednisone/prednisolone — DRUG
    Premedication with 100mg intravenous prednisone/prednisolone 30-60 minutes before obinutuzumab infusion.
  • Methylprednisolone — DRUG
    Premedication with intravenous methylprednisolone 80mg 30-60 minutes before obinutuzumab infusion.
  • CT Scan chest/abdomen/pelvis — DIAGNOSTIC_TEST
    Screening, baseline, window Cycle -1/pre cycle 1, cycles 6-12; cycles 3-9, end of treatment and follow-up.
  • MRI — DIAGNOSTIC_TEST
    Screening, baseline, window Cycle -1/pre cycle 1, cycles 6-12; cycles 3-9, end of treatment and follow-up.
  • 18-FDG-PET — DIAGNOSTIC_TEST
    Baseline, Cycle -1, Day 1, window Cycle -1/pre cycle 1, cycles 6-12, end of treatment and follow-up.
  • Bone Marrow Biopsy — PROCEDURE
    Screening, Cycle 7-12, Day 1 and end of treatment.
  • Bone Marrow Aspiration — PROCEDURE
    Screening, Cycle 7-12, Day 1 and end of treatment.

Study Details

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.

Key Dates

Start date
Dec 16, 2021
Status verified
Jan 2025
Primary completion
Mar 29, 2024
Completion
Jun 20, 2024

Study Design

Enrollment
11 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Experimental treatment: FL dose expansion
    Window of magrolimab intravenous (IV) with a 1 mg/kg priming dose followed by 30mg/kg loading and maintenance doses + obinutuzumab IV 1000mg combination for two (2) cycles (28-days each, Cycles -2 and -1), then venetoclax will be added at target dose (dose determined from Arm 1). Triplet combination treatment with magrolimab + obinutuzumab + venetoclax will be 6 cycles (28-days each, Cycles 1-6); further treatment will be response-adapted.
  • Experimental: Experimental treatment: FL Dose-finding
    Magrolimab intravenous (IV) with a 1 mg/kg priming dose followed by 30mg/kg loading and maintenance doses + obinutuzumab IV 1000mg + venetoclax 800mg by mouth (PO) combination administered to 6 patients for six (6) cycles (28-days each, Cycles 1-6); further treatment with additional cycles will be response-adapted. Note: Dose-limiting toxicity (DLT) assessment of the magrolimab + obinutuzumab + venetoclax triplet will take place during Cycle 1. If =2 patients experience DLT, an additional 6 patients will be enrolled at Dose level (DL (-1) of venetoclax 600mg with magrolimab and obinutuzumab.
  • Experimental: Experimental treatment: MZL, MCL, and CLL Dose-finding
    Magrolimab intravenous (IV) with a 1 mg/kg priming dose followed by 30mg/kg loading and maintenance doses + obinutuzumab IV 1000mg + venetoclax ramp-up to target dose of 400mg over 5 weeks (35 days, Cycle 1) administered to 6 patients. Triplet combination of magrolimab + obinutuzumab + venetoclax (target dose, no ramp-up) will continue for five (5) additional cycles (28-days each, Cycles 2-6); further treatment with additional cycles will be response-adapted. Note: Dose-limiting toxicity (DLT) assessment of the magrolimab + obinutuzumab + venetoclax triplet will take place during Cycle 1. If =2 patients experience DLT, an additional 6 patients will be enrolled at Dose level (DL (-1) of venetoclax 200mg with magrolimab and obinutuzumab.
  • Experimental: Experimental treatment: mzl, MCL, CLL dose expansion
    Window of magrolimab intravenous (IV) with a 1 mg/kg priming dose followed by 30mg/kg loading and maintenance doses + obinutuzumab IV 1000mg combination for two (2) cycles (28-day cycles, Cycles -2 and -1), then venetoclax safety ramp-up to target dose (dose determined from Arm 2) over 5 weeks (35-days, Cycle 1). Triplet combination treatment with magrolimab + obinutuzumab + venetoclax (target dose, no ramp-up) will continue for 5 additional cycles (28-days each, Cycles 2-6); further treatment will be response-adapted.

Primary Outcome Measure

Number of Grades 3, 4, and/or 5 Dose-limiting Toxicities (DLT) Probably and/or Definitely Related to Triplet Combination Therapy [ Time Frame: 4 weeks for Arm 1 and 5 weeks for Arm 2 ]

Locations (1)

FacilityCityStateZIPSite coordinators
National Institutes of Health Clinical CenterBethesdaMaryland20892-

Find similar trials in Bethesda, MD

By research site
National Institutes of Health Clinical Center· Bethesda, MD

Related Studies