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Lenalidomide and GA101 in Relapsed Indolent Non-Hodgkin's Lymphoma

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ClinicalTrials.gov Identifier: NCT01995669
Recruitment Status : Recruiting
First Posted : November 26, 2013
Last Update Posted : August 6, 2018
Sponsor:
Collaborators:
Celgene
Genentech, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to find the highest tolerable dose of the combination of GA101 (obinutuzumab) and lenalidomide that can be given to patients with indolent NHL. The study will also look at how well the two drugs work together to control the disease.

This is an investigational study. Lenalidomide is FDA approved for the treatment of multiple myeloma (MM) and myelodysplastic syndrome (MDS). Obinutuzumab is FDA approved and commercially available for the treatment of chronic lymphocytic leukemia (CLL). Its use in this study is investigational. The combination of lenalidomide and obinutuzumab is investigational.

Up to 72 participants will be enrolled on this study. All will be enrolled at MD Anderson.


Condition or disease Intervention/treatment Phase
Lymphoma Drug: Lenalidomide Drug: Obinutuzumab (GA101) Phase 1 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Lenalidomide and Obinutuzumab (GA101) in Relapsed Indolent Non-Hodgkin's Lymphoma
Actual Study Start Date : May 2014
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : May 2019


Arm Intervention/treatment
Experimental: Relapsed/Refractory Indolent Lymphoma Group

Phase I: Lenalidomide starting dose of 10 mg taken orally in the morning each day on days 2 - 22, followed by 6 days of no therapy of each 28-day cycle.

Phase I: Obinutuzumab (GA101) 1000 mg given by vein on day 1, 2, 8, and 15 of cycle one and on day 1 of each subsequent cycle up to 6 cycles. Obinutuzumab given in divided doses on cycle 1; 100 mg by vein on day 1, and 900 mg by vein on day 2, subsequent doses given over 1 day.

Drug: Lenalidomide

Phase I Starting Dose: 10 mg by mouth on Days 2-22 of Cycles 1-6. Each cycle is 28 days. Participants with diagnosis of small lymphocytic lymphoma (SLL) begin cycle #1 at a maximum dose of 10 mg total daily on days 2 to 22 of a 28 day cycle. Dose escalated by 5 mg each cycle up to MTD if no toxicity is encountered.

Phase II: Lenalidomide administered orally at maximum tolerated dose (MTD) from Phase I on days 2 to 22 of a 28 day cycle in participants with follicular lymphoma and marginal zone lymphoma.

Other Names:
  • CC-5013
  • Revlimid

Drug: Obinutuzumab (GA101)

Phase I: 1000 mg by vein on Day 1, 8, 15, and 22 of cycle one and on day 1 of each subsequent cycle up to 6 cycles during lenalidomide dosing.

Phase II and Maintenance: 1000 mg by vein - Extended dosing of obinutuzumab begins after 6 cycles of combination therapy if participant demonstrates at least stable disease on response assessment. In extended dosing schedule, obinutuzumab administered every 2 months, and in absence of progression, dosed for maximum of 30 months (combination + maintenance).

Other Name: GA101

Experimental: Cohort B - Non-Follicular Indolent Lymphoma

Phase II: Lenalidomide capsules taken orally daily each day on days 2 - 22, followed by 6 days of no therapy of each 28-day cycle at the MTD tolerated in Phase I.

Phase II: Participants with diagnosis of small lymphocytic lymphoma (SLL) begin cycle #1 at a maximum dose of Lenalidomide 10 mg total on days 2 to 22 of a 28 day cycle. Dose escalated by 5 mg each cycle up to MTD if no toxicity is encountered.

Phase II: Obinutuzumab (GA101) 1000 mg given by vein on day 1 every 2 months for 2 years.

Drug: Lenalidomide

Phase I Starting Dose: 10 mg by mouth on Days 2-22 of Cycles 1-6. Each cycle is 28 days. Participants with diagnosis of small lymphocytic lymphoma (SLL) begin cycle #1 at a maximum dose of 10 mg total daily on days 2 to 22 of a 28 day cycle. Dose escalated by 5 mg each cycle up to MTD if no toxicity is encountered.

Phase II: Lenalidomide administered orally at maximum tolerated dose (MTD) from Phase I on days 2 to 22 of a 28 day cycle in participants with follicular lymphoma and marginal zone lymphoma.

Other Names:
  • CC-5013
  • Revlimid

Drug: Obinutuzumab (GA101)

Phase I: 1000 mg by vein on Day 1, 8, 15, and 22 of cycle one and on day 1 of each subsequent cycle up to 6 cycles during lenalidomide dosing.

Phase II and Maintenance: 1000 mg by vein - Extended dosing of obinutuzumab begins after 6 cycles of combination therapy if participant demonstrates at least stable disease on response assessment. In extended dosing schedule, obinutuzumab administered every 2 months, and in absence of progression, dosed for maximum of 30 months (combination + maintenance).

Other Name: GA101

Experimental: Cohort A - Relapsed/Refractory Follicular Lymphoma

Phase II: Lenalidomide capsules taken orally daily each day on days 2 - 22, followed by 6 days of no therapy of each 28-day cycle at the MTD tolerated in Phase I.

Phase II: Obinutuzumab (GA101) 1000 mg given by vein on day 1 every 2 months for 2 years.

Drug: Lenalidomide

Phase I Starting Dose: 10 mg by mouth on Days 2-22 of Cycles 1-6. Each cycle is 28 days. Participants with diagnosis of small lymphocytic lymphoma (SLL) begin cycle #1 at a maximum dose of 10 mg total daily on days 2 to 22 of a 28 day cycle. Dose escalated by 5 mg each cycle up to MTD if no toxicity is encountered.

Phase II: Lenalidomide administered orally at maximum tolerated dose (MTD) from Phase I on days 2 to 22 of a 28 day cycle in participants with follicular lymphoma and marginal zone lymphoma.

Other Names:
  • CC-5013
  • Revlimid

Drug: Obinutuzumab (GA101)

Phase I: 1000 mg by vein on Day 1, 8, 15, and 22 of cycle one and on day 1 of each subsequent cycle up to 6 cycles during lenalidomide dosing.

Phase II and Maintenance: 1000 mg by vein - Extended dosing of obinutuzumab begins after 6 cycles of combination therapy if participant demonstrates at least stable disease on response assessment. In extended dosing schedule, obinutuzumab administered every 2 months, and in absence of progression, dosed for maximum of 30 months (combination + maintenance).

Other Name: GA101




Primary Outcome Measures :
  1. 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 first course of each cohort (28 days), and refers to a medically significant event which meets criteria using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.



Secondary Outcome Measures :
  1. Objective Response [ Time Frame: Following six 28 day cycles and up to one year ]
    Objective response (complete response + partial response) after 6 cycles and DLT after 1 cycle monitored simultaneously using the Bayesian approach of Thall, Simon, Estey as extended by Thall and Sung. Response criteria for 1999 International Workshop (IWG) on Response Criteria for NHL: All responses characterized as either complete remission (CR), unconfirmed complete remission (CRu), partial remission (PR), stable disease (SD), or progression of disease (POD). Response assessed after every three cycles of combination therapy then assessed every 4 months thereafter while receiving obinutuzumab maintenance treatment.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. A diagnosis of small lymphocytic lymphoma, follicular lymphoma (grades 1-3a), or marginal zone lymphoma.
  2. Evidence of progression or lack of response following at least 1 prior treatment for indolent lymphoma.
  3. Able and willing to provide written informed consent and to comply with the study protocol
  4. Age >/= 18 years
  5. Must have at least 1 node greater than 1.5cm in short axis diameter
  6. • Adequate hematologic function (unless abnormalities are related to NHL), defined as follows: †† - Hemoglobin >/= 9.0 g/dL - Absolute neutrophil count >/= 1.5 x 10v9/L - Platelet count >/= 75 x 10v9/L - ANC < 1.5 x 10v9 /L or PLT count less than 100 x10v9/L if cytopenia is due to extensive bone marrow involvement of disease as determined by the treating physician.
  7. 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
  8. 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
  9. 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).
  10. All study participants must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of Revlimid REMS® program.
  11. For patients with bulky disease (tumors >5cm); must be able to take aspirin (81mg or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin.
  12. 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:

  1. Evidence ongoing transformation into aggressive NHL.
  2. History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
  3. Known hypersensitivity to thalidomide or lenalidomide.
  4. 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
  5. 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
  6. 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)
  7. 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)
  8. Vaccination with live vaccines within 28 days prior to start of treatment
  9. 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); AST or ALT > 2.5 x ULN; Total bilirubin > 1.5 x ULN (or > 3 x ULN for patients with documented Gilbert syndrome).
  10. Any history of hepatitis B infection.
  11. Positive test results for hepatitis C (hepatitis C virus [HCV] antibody serology testing) Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA
  12. Known history of HIV seropositive status
  13. 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)
  14. Pregnant or lactating
  15. Eastern Cooperative Oncology Group (ECOG) performance status greater than 2
  16. Participation in another clinical trial with drug intervention within 21 days prior to start of Cycle 1 and during the study
  17. Patients with SLL/CLL are excluded during the phase I portion of the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01995669


Contacts
Contact: Nathan Fowler, MD 713-792-2860

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Celgene
Genentech, Inc.
Investigators
Principal Investigator: Nathan Fowler, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01995669     History of Changes
Other Study ID Numbers: 2013-0261
NCI-2014-00943 ( Registry Identifier: NCI CTRP )
First Posted: November 26, 2013    Key Record Dates
Last Update Posted: August 6, 2018
Last Verified: August 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Lymphoma
Relapsed Indolent Non-Hodgkin's Lymphoma
non-Hodgkin's lymphoma
NHL
Relapsed/refractory indolent lymphoma
Small lymphocytic lymphoma
SLL
Follicular lymphoma
Marginal zone lymphoma
Lenalidomide
CC-5013
Revlimid
Obinutuzumab
GA101

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lenalidomide
Thalidomide
Obinutuzumab
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents