Rituximab + Immunotherapy in Follicular Lymphoma

NCT03636503 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: 18-311
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 6

Brief Summary

This research study is studying several new investigational drug combinations as a possible treatment for follicular lymphoma. The drugs involved are:

• Rituximab
• Utomilumab
• Avelumab
• PF-04518600

Conditions

Follicular Lymphoma

Keywords

Lymphoma

Outcome Measures

Primary Outcomes (2)

• Recommended Phase 2 Dosing

  Patients assessed for DLT after each 28-day cycle of treatment. Up to two cohorts of 3 patients per dose level plus expansion cohort. Rituximab/Utomilumab/Avelumab arm assessed 2 dose levels. Rituximab/Utomilumab/PF04518600 assessed 3 dose levels. Rituximab/PF04518600/Avelumab assessed 2 dose levels.

  6 months total, assessed after each 28-day cycle

• Number of Participants With Complete Response Per Lugano Criteria

  Per 2014 Lugano criteria, a complete response is defined as PET-CT, score 1, 2, or 3\* with or without a residual mass on 5PS Or on CT, target nodes/nodal masses must regress to ≤ 1.5 cm in LDi, and no extralymphatic sites of disease

  Response assessed after completing treatment (6 months)

Secondary Outcomes (10)

• Number of Participants With Partial Response Per Lugano Criteria

  Response assessed after completing treatment (6 months)

• Number of Participants With Objective Response Per Lugano Criteria

  Response assessed after completing treatment (6 months)

• Number of Participants With Objective Response Per LYRIC Criteria

  Response assessed after completing treatment (6 months)

• Number of Participants With Complete Response Per LYRIC Criteria

  Response assessed after completing treatment (6 months)

• Progression-Free Survival Per Lugano Criteria

  6 cycles (approximately 6 months) of treatment followed by 24 months of active follow-up with contact every 3 months

Study Arms (7)

Rituximab+Utomilumab+Avelumab-3mg

EXPERIMENTAL

* Rituximab is administered intravenously per institutional standards for four weekly treatments for cycle 1 only * Utomilumab is administered intravenously over 1 hour once every 4 weeks * Avelumab is administered intravenously over 1 hour once every 2 weeks, 3mg/kg

Drug: Rituximab; Drug: Utomilumab; Drug: Avelumab

Rituximab+Utomilumab+Avelumab-10mg

EXPERIMENTAL

* Rituximab is administered intravenously per institutional standards for four weekly treatments for cycle 1 only * Utomilumab is administered intravenously over 1 hour once every 4 weeks * Avelumab is administered intravenously over 1 hour once every 2 weeks, 10mg/kg

Drug: Rituximab; Drug: Utomilumab; Drug: Avelumab

PF04518600-0.3mg

EXPERIMENTAL

-PF-04518600 is administered intravenously over 1 hour on day 1 and day 15, 0.3mg/kg

Drug: PF04518600

Rituximab+PF04518600-0.3mg

EXPERIMENTAL

* Rituximab is administered intravenously per institutional standards for four weekly treatments for cycle 1 only * PF-04518600 is administered intravenously over 1 hour on day 1 and day 15, 0.3mg/kg

Drug: Rituximab; Drug: PF04518600

Rituximab+Utomilumab+PF04518600-0.3mg

EXPERIMENTAL

* Rituximab is administered intravenously per institutional standards for four weekly treatments for cycle 1 only * Utomilumab is administered intravenously over 1 hour once every 4 weeks * PF-04518600 is administered intravenously over 1 hour on day 1 and day 15, 0.3mg/kg

Drug: Rituximab; Drug: Utomilumab; Drug: PF04518600

Rituximab+PF04518600-0.3mg+Avelumab-3mg

EXPERIMENTAL

* Rituximab is administered intravenously per institutional standards for four weekly treatments for cycle 1 only * Utomilumab is administered intravenously over 1 hour once every 4 weeks * Avelumab is administered intravenously over 1 hour once every 2 weeks, 3mg/kg

Drug: Rituximab; Drug: Avelumab; Drug: PF04518600

Rituximab+PF04518600-0.3mg+Avelumab-10mg

EXPERIMENTAL

* Rituximab is administered intravenously per institutional standards for four weekly treatments for cycle 1 only * Utomilumab is administered intravenously over 1 hour once every 4 weeks * Avelumab is administered intravenously over 1 hour once every 2 weeks, 10mg/kg

Drug: Rituximab; Drug: Avelumab; Drug: PF04518600

Interventions

Rituximab DRUG

Rituximab works by targeting the CD20 antigen on normal and malignant B-cells. Then the body's natural immune defenses are recruited to attack and kill the marked B-cells. Stem cells (young cells in the bone marrow that will develop into the various types of cells) do not have the CD20 antigen. This allows healthy B-cells to regenerate after treatment

Also known as: Rituxan

Rituximab+PF04518600-0.3mg; Rituximab+PF04518600-0.3mg+Avelumab-10mg; Rituximab+PF04518600-0.3mg+Avelumab-3mg; Rituximab+Utomilumab+Avelumab-10mg; Rituximab+Utomilumab+Avelumab-3mg; Rituximab+Utomilumab+PF04518600-0.3mg

Utomilumab DRUG

Utomilumab is a drug which may stimulate the immune system against tumor cells. Because it activate the immune system, it is sometimes called immunotherapy drug

Also known as: PF-05082566, PF05082566

Rituximab+Utomilumab+Avelumab-10mg; Rituximab+Utomilumab+Avelumab-3mg; Rituximab+Utomilumab+PF04518600-0.3mg

Avelumab DRUG

Avelumab is a drug which may stimulate the immune system against tumor cells. Because it activate the immune system, it is sometimes called immunotherapy drug

Also known as: Bavencio

Rituximab+PF04518600-0.3mg+Avelumab-10mg; Rituximab+PF04518600-0.3mg+Avelumab-3mg; Rituximab+Utomilumab+Avelumab-10mg; Rituximab+Utomilumab+Avelumab-3mg

PF04518600 DRUG

In the presence of tumor-associated antigens (TAAs), this may promote a T-cell-mediated immune response against TAA-expressing tumor cells. OX40

Also known as: PF-04518600

PF04518600-0.3mg; Rituximab+PF04518600-0.3mg; Rituximab+PF04518600-0.3mg+Avelumab-10mg; Rituximab+PF04518600-0.3mg+Avelumab-3mg; Rituximab+Utomilumab+PF04518600-0.3mg

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically determined follicular lymphoma, grade 1-3A, with pathologic review at the participating institutions, that has either:
• Relapsed or primary refractory after at least one line of therapy including anti-CD-20 monoclonal antibody treatment (part A) or;
• Has had no previous anti-lymphoma therapy other than corticosteroids or radiotherapy (part B).
• Patients with active histologic transformation are excluded. Relapsed/refractory patients with prior transformation may be included as long as there is no evidence of transformation at the time of study entry by pathology, imaging, or clinical status
• Patients in part B, without prior anti-lymphoma therapy, must be in need of treatment as defined by any of the following criteria:
• Symptomatic adenopathy
• Organ function impairment due to disease involvement, including cytopenias due to marrow involvement (WBC \<1.5x109/L; absolute neutrophil count \[ANC\] \<1.0x109/L, Hgb \<10g/dL; platelets \<100x109/L)
• Constitutional symptoms
• Maximum diameter of disease \> 7cm
• \>3 nodal sites of involvement
• Risk of local compressive symptoms
• Splenomegaly (craniocaudal diameter \> 16cm on CT imaging)
• Clinically significant pleural or peritoneal effusion
• Leukemic phase (\>5x109/L circulating malignant cells)
• Rapid generalized disease progression

You may not qualify if:

• Patients currently receiving anticancer therapies or who have received anticancer therapies within 28 days of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.), or 56 days for radioimmunotherapy. Steroids for symptom palliation are allowed, but must be either discontinued or on stable doses of \< 10mg daily of prednisone (or the equivalent) at the time of initiation of protocol therapy.
• Patients may not be receiving any other investigational agents, or have received investigational agents within 4 weeks (or 3 half-lives, whichever is longer) of beginning treatment.
• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy unless in consultation with an allergy specialist they are deemed eligible for retreatment with desensitization.
• Patients who have previously received therapy with any drug that works by a similar mechanism of action as any drug being tested in a given cohort will be excluded from that cohort but will be allowed to enroll in other open cohorts.
• Patients who have undergone prior allogeneic stem cell transplantation
• Patients with a history of or active autoimmune disease (except controlled asthma, Hashimoto thyroiditis, atopic dermatitis, and/or vitiligo), or requiring systemic corticosteroids at a dose of 10mg prednisone equivalent daily. Patients with a history of autoimmune disease who never required corticosteroids and with no evidence of disease activity, and in whom the risk of reactivation is felt not to be serious, may be enrolled after discussion with the overall study chair. Exceptions to this are patients with a history of inflammatory bowel disease (ulcerative colitis and Crohn's disease). These patients are excluded regardless of whether their disease is active or inactive.
• Patients with active pneumonitis or colitis, or patients with chronic liver disease and/or cirrhosis
• Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study.
• Patients with known leptomeningeal or brain metastases. Imaging or spinal fluid analysis to exclude CNS involvement is not required, unless there is clinical suspicion by the treating investigator.
• Patients with known HIV infection or hepatitis B or C infection. Testing for HIV is optional. Testing for hepatitis B and C is mandatory. Patients with hepatitis B core Ab positivity but negative surface antigen and negative viral load may be enrolled if they can be treated with a prophylactic agent (eg, entecavir); patients with hepatitis C seropositivity who have undergone successful treatment with negative viral load can also be enrolled.
• Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
• Prior history of another malignancy (except for non-melanoma skin cancer or in situ cervical or breast cancer) unless disease free for at least three years. Patients with prostate cancer are allowed if PSA is less than 1.
• Patients should not have received immunization with attenuated live vaccine within one week of study entry or during study period.
• Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. Women of child bearing potential (WOCBP) or male study participants of reproductive potential must agree to use double barrier birth control method of contraception during the course of the study treatment period and for 3 months after completing study treatment. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who are not postmenopausal (no menses) for at least 12 consecutive months. WOCBP must have a negative urine or serum pregnancy test within 14 days prior to administration of treatment.
• History of noncompliance to medical regimens.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Pfizer: collaborator

Study Sites (6)

City of Hope

Duarte, California, 91010, United States

Location

Yale New-Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63130, United States

Location

Related Publications (1)

• Merryman RW, Redd RA, Freedman AS, Ahn IE, Brown JR, Crombie JL, Davids MS, Fisher DC, Jacobsen ED, Kim AI, LaCasce AS, Ng S, Odejide OO, Parry EM, Isufi I, Kline J, Cohen JB, Mehta-Shah N, Bartlett NL, Mei M, Kuntz TM, Wolff J, Rodig SJ, Armand P, Jacobson CA. A multi-cohort phase 1b trial of rituximab in combination with immunotherapy doublets in relapsed/refractory follicular lymphoma. Ann Hematol. 2024 Jan;103(1):185-198. doi: 10.1007/s00277-023-05475-0. Epub 2023 Oct 18.

  PMID: 37851072 DERIVED

MeSH Terms

Conditions

Lymphoma, Follicular; Lymphoma

Interventions

Rituximab; utomilumab; avelumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

This trial was terminated early due to drug manufacturer discontinuing drug and no longer supplying.

Results Point of Contact

• Title: Caron Jacobson, MD
• Organization: Dana-Farber Cancer Institute

caron_jacobson@dfci.harvard.edu

617-632-6404

Study Officials

• Caron A. Jacobson, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 2, 2018
• First Posted: August 17, 2018
• Study Start: October 30, 2018
• Primary Completion: July 23, 2021
• Study Completion: July 30, 2023
• Last Updated: February 6, 2025
• Results First Posted: February 6, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)