Lenalidomide and Obinutuzumab in Treating Patients With Relapsed Indolent Non-Hodgkin Lymphoma

NCT01995669 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: 2013-0261NCI-2014-00943ML28301
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects and best dose of lenalidomide when given together with obinutuzumab and how well this combination works in treating patients with low-grade non-Hodgkin lymphoma (NHL) that has returned after a period of improvement (relapsed). Biological therapies, such as lenalidomide, may attack specific cancer cells and stop them from growing or kill them. Obinutuzumab is a form of targeted therapy because it attaches itself to specific molecules (receptors) on the surface of cancer cells, known as CD20 receptors. When obinutuzumab attaches to CD20 receptors, the signals that tell the cells to grow are blocked and the cancer cell may be marked for destruction by the body's immune system. Giving lenalidomide and obinutuzumab together may work better in treating NHL.

Conditions

Grade 3a Follicular Lymphoma; Recurrent Follicular Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Follicular Lymphoma; Refractory Marginal Zone Lymphoma; Refractory Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose of Lenalidomide When Given With Obinutuzumab Defined as the Highest Dose Level Have Been Treated With Less Than 2 Instances of Dose Limiting Toxicity DLT.

  To determine the maximum tolerated dose of lenalidomide plus obinutuzumab in relapsed/refractory indolent lymphoma the 3 by 3 method was used. (Phase I) Doses of Lenalidomide to be used are 10mg, 15mg, 20mg in Phase 1.

  28 days after 168 days (6 courses)

Secondary Outcomes (1)

• Overall Survival, Time to Progression, and Progression Free Survival (Phase II)

  up to 4 years

Study Arms (1)

Treatment (lenalidomide, obinutuzumab)

EXPERIMENTAL

Patients receive lenalidomide PO QD on days on days 2-22 and obinutuzumab IV over 4-5 hours on days 1, 2, 8, 15, and 22 of cycle 1 and on day 1 of each subsequent cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients not experiencing progression and who in the opinion of treating physician are deriving benefit from combination treatment may continue lenalidomide for an additional 6 cycles (up to cycle 12) and obinutuzumab on day 1 every 2 months for up to 2 years in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Drug: Lenalidomide; Biological: Obinutuzumab

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (lenalidomide, obinutuzumab)

Lenalidomide DRUG

Given PO

Also known as: CC-5013, CC5013, CDC 501, Revlimid

Treatment (lenalidomide, obinutuzumab)

Obinutuzumab BIOLOGICAL

Given IV

Also known as: Anti-CD20 Monoclonal Antibody R7159, GA-101, GA101, Gazyva, huMAB(CD20), R7159, RO 5072759, RO-5072759, RO5072759

Treatment (lenalidomide, obinutuzumab)

Eligibility Criteria

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

You may qualify if:

• A diagnosis of small lymphocytic lymphoma, follicular lymphoma (grades 1-3a), or marginal zone lymphoma
• Evidence of progression or lack of response following at least 1 prior treatment for indolent lymphoma
• Able and willing to provide written informed consent and to comply with the study protocol
• Must have at least 1 node greater than 1.5 cm in short axis diameter
• Adequate hematologic function (unless abnormalities are related to NHL), defined as follows:
• Hemoglobin \>= 9.0 g/dL
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L; ANC \< 1.5 x 10\^9/L if cytopenia is due to extensive bone marrow involvement of disease as determined by the treating physician
• Platelet count (PLT) \>= 75 x 10\^9/L; PLT count less than 100 x 10\^9/L if cytopenia is due to extensive bone marrow involvement of disease as determined by the treating physician
• For men who are not surgically sterile, agreement to use a barrier method of contraception for \>= 3 months after the last obinutuzumab dose; in addition, male patients must agree to request that their partners use an additional method of contraception, such as oral contraceptives, intrauterine device, barrier method of contraception, or spermicidal jelly
• For women of reproductive potential who are not surgically sterile, agreement to use two adequate methods of contraception, such as oral contraceptives, intrauterine device, or barrier method of contraception in conjunction with spermicidal jelly for \>= 12 months after the last obinutuzumab dose
• Females of childbearing potential (FCBP) must have a negative serum pregnancy test with a sensitivity of at least 50 mIU/mL within 10-14 days prior to and again within 24 hours of prescribing lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a female of child bearing potential even if they have had a successful vasectomy
• A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
• All study participants must be registered into the mandatory Revlimid Risk Evaluation and Mitigation Strategy (REMS) program, and be willing and able to comply with the requirements of Revlimid REMS program
• For patients with bulky disease (tumors \> 5 cm); must be able to take aspirin (81 mg or 325 mg) daily as prophylactic anticoagulation (patients intolerant to acetylsalicylic acid \[ASA\] may use warfarin or low molecular weight heparin)
• Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS program; able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin)

You may not qualify if:

• Evidence ongoing transformation into aggressive NHL
• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
• Known hypersensitivity to thalidomide or lenalidomide
• Regular treatment with corticosteroids during the 4 weeks prior to the start of cycle 1, unless administered for indications other than NHL at a dose equivalent to =\< 30 mg/day prednisone
• History of prior malignancy within the last 5 years, with the exception of curatively treated basal or squamous cell carcinoma of the skin and low-grade in situ carcinoma of the cervix
• Evidence or history of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association class III or IV cardiac disease, severe arrhythmia, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina) or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics, except if for tumor fever) within 4 weeks prior to the start of cycle 1; patients with suspected active or latent tuberculosis (latent tuberculosis needs to be confirmed by positive interferon-gamma release assay)
• Vaccination with live vaccines within 28 days prior to start of treatment
• Any of the following abnormal laboratory values (unless any of these abnormalities are due to underlying lymphoma)
• Creatinine \> 1.5 times the upper limit of normal (ULN) (unless creatinine clearance normal), or calculated creatinine clearance \< 40 mL/min (using Cockcroft-Gault formula)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2.5 x ULN
• Total bilirubin \> 1.5 x ULN (or \> 3 x ULN for patients with documented Gilbert syndrome)
• Any history of hepatitis B infection
• Positive test results for hepatitis C (hepatitis C virus \[HCV\] antibody serology testing); patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA)
• Known history of human immunodeficiency virus (HIV) seropositive status

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Gurumurthi A, Chin CK, Feng L, Fowler NH, Strati P, Hagemeister FB, Fayad LE, Westin JR, Obi C, Arafat J, Nair R, Steiner RE, Neelapu SS, Flowers CR, Nastoupil LJ. Safety and activity of lenalidomide in combination with obinutuzumab in patients with relapsed indolent non-Hodgkin lymphoma: a single group, open-label, phase 1/2 trial. EClinicalMedicine. 2024 Jul 27;74:102747. doi: 10.1016/j.eclinm.2024.102747. eCollection 2024 Aug.

  PMID: 39161543 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center

MeSH Terms

Conditions

Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Lenalidomide; obinutuzumab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr. Loretta Nastoupil
• Organization: University of Texas M D Anderson Cancer Center

lnastoupil@mdanderson.org

(713) 792-2860

Study Officials

• Loretta Nastoupil

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2013
• First Posted: November 26, 2013
• Study Start: May 27, 2014
• Primary Completion: January 23, 2023
• Study Completion: January 23, 2023
• Last Updated: June 24, 2025
• Results First Posted: June 24, 2025

Record last verified: 2025-06

Locations

US (1)