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

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ClinicalTrials.gov Identifier: NCT01995669
Recruitment Status : Active, not recruiting
First Posted : November 26, 2013
Last Update Posted : July 23, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE November 20, 2013
First Posted Date  ICMJE November 26, 2013
Last Update Posted Date July 23, 2021
Actual Study Start Date  ICMJE May 21, 2014
Estimated Primary Completion Date May 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 20, 2019)
  • Maximum tolerated dose of lenalidomide when given with obinutuzumab defined as the highest dose level in which 6 patients have been treated with less than 2 instances of dose limiting toxicity (DLT) (Phase I) [ Time Frame: 28 days ]
    Will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4. Toxicity type and severity by dose level will be summarized using frequency tables.
  • Incidence of DLTs after course 1 assessed using NCI CTCAE version 4 (Phase II) [ Time Frame: After 28 days (1 course) ]
    Toxicity type and severity will be summarized for each patient cohort using frequency tables.
  • Overall response rate (complete response + partial response) (Phase II) [ Time Frame: After 168 days (6 courses) ]
    The overall response rate for each patient cohort will be calculated and the Clopper Pearson confidence interval will be provided. Chi square test or Fisher's exact test will be used to evaluate the association between patient prognostic factor and response.
Original Primary Outcome Measures  ICMJE
 (submitted: November 20, 2013)
Maximum Tolerated Dose (MTD) of Lenalidomide plus Obinutuzumab [ Time Frame: 28 days ]
Maximum tolerated dose (MTD) defined as the highest dose level in which 6 patients have been treated with less than 2 instances of dose limiting toxicity (DLT). Dose limiting toxicity (DLT) assessed during the first course of each cohort (28 days).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 20, 2019)
  • Overall survival [ Time Frame: Up to 4 years ]
    The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
  • Progression-free survival [ Time Frame: Up to 4 years ]
    The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 20, 2013)
Objective Response [ Time Frame: After 6, 28 day cycles ]
The objective response (complete response + partial response) determined after 6 cycles. The distribution of time-to-event endpoints including overall survival and progression free survival estimated using the method of Kaplan and Meier.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Lenalidomide and Obinutuzumab in Treating Patients With Relapsed Indolent Non-Hodgkin Lymphoma
Official Title  ICMJE A Phase I/II Study of Lenalidomide and Obinutuzumab (GA101) in Relapsed Indolent Non-Hodgkin's Lymphoma
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.
Detailed Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose of lenalidomide plus obinutuzumab in relapsed/refractory indolent lymphoma. (Phase I) II. To evaluate the safety of lenalidomide in combination with obinutuzumab in patients with relapsed/refractory indolent lymphoma. (Phase II) III. To determine the overall response rate (ORR) of the combination in patients with relapsed/refractory indolent lymphoma. (Phase II)

SECONDARY OBJECTIVES:

I. To determine the complete response rate, time to progression (TTP), and progression free survival in patients with indolent lymphoma following treatment with obinutuzumab + lenalidomide.

II. To evaluate changes in immune effector cells and the tumor microenvironment following treatment with obinutuzumab + lenalidomide.

OUTLINE: This is a phase I, dose-escalation study of lenalidomide followed by a phase II study.

Patients receive lenalidomide orally (PO) once daily (QD) on days 2-22 and obinutuzumab intravenously (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.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 1 year, and then yearly thereafter.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Drug: Lenalidomide
    Given PO
    Other Names:
    • CC-5013
    • CC5013
    • CDC 501
    • Revlimid
  • Biological: Obinutuzumab
    Given IV
    Other Names:
    • Anti-CD20 Monoclonal Antibody R7159
    • GA-101
    • GA101
    • Gazyva
    • huMAB(CD20)
    • R7159
    • RO 5072759
    • RO-5072759
    • RO5072759
Study Arms  ICMJE Experimental: Treatment (lenalidomide, obinutuzumab)
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.
Interventions:
  • Other: Laboratory Biomarker Analysis
  • Drug: Lenalidomide
  • Biological: Obinutuzumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: July 16, 2020)
78
Original Estimated Enrollment  ICMJE
 (submitted: November 20, 2013)
72
Estimated Study Completion Date  ICMJE May 31, 2022
Estimated Primary Completion Date May 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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
  • Positive test results for human T-lymphotropic 1 (HTLV 1) virus; HTLV testing is required in patients from endemic countries (Japan, countries in the Caribbean basin, South America, Central America, Sub Saharan Africa, and Melanesia)
  • Pregnant or lactating
  • Eastern Cooperative Oncology Group (ECOG) performance status greater than 2
  • Participation in another clinical trial with drug intervention within 21 days prior to start of cycle 1 and during the study
  • Patients with small lymphocytic lymphoma (SLL)/chronic lymphocytic leukemia (CLL) are excluded during the phase I portion of the study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01995669
Other Study ID Numbers  ICMJE 2013-0261
NCI-2014-00943 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
ML28301
2013-0261 ( Other Identifier: M D Anderson Cancer Center )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party M.D. Anderson Cancer Center
Study Sponsor  ICMJE M.D. Anderson Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Loretta Nastoupil M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP