Lenalidomide in Combination With Rituximab in Treating Participants With Stage III/IV Indolent Non-Hodgkin Lymphoma
Study Details
Study Description
Brief Summary
This phase II trial studies how well lenalidomide works in combination with rituximab in treating participants with stage III-IV non-Hodgkin lymphoma that is growing slowly. Lenalidomide is designed to change the body's immune system. It may also interfere with the development of tiny blood vessels that help support tumor growth, which may prevent the growth of cancer cells. Monoclonal antibodies, such as rituximab, may interfere with the ability of cancer cells to grow and spread. Giving lenalidomide and rituximab may work better in participants with indolent non-Hodgkin lymphoma.
Detailed Description
PRIMARY OBJECTIVES:
- To evaluate the overall response rate of lenalidomide in combination with rituximab in previously untreated indolent non-Hodgkin's lymphoma (NHL).
SECONDARY OBJECTIVES:
- To evaluate the toxicity of lenalidomide in combination with rituximab in previously untreated indolent non-Hodgkin's lymphoma.
OUTLINE: Participants are assigned to 1 of 2 drug schedules.
SCHEDULE A: Participants receive lenalidomide orally (PO) on days 1-21 and rituximab intravenously (IV) over 4-8 hours on day 1 of courses 1-12. Courses repeat every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
SCHEDULE B: Participants receive lenalidomide PO on days 2-22 and rituximab IV over 4-8 hours on days 1, 8, 15, and 22 of course 1 and on day 1 of all subsequent courses. Courses repeat every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, participants are followed up every 6 months.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Schedule A (lenalidomide, rituximab) Participants receive lenalidomide PO on days 1-21 and rituximab IV over 4-8 hours on day 1 of courses 1-12. Courses repeat every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity |
Drug: Lenalidomide
Given PO
Other Names:
Biological: Rituximab
Given IV
Other Names:
|
| Experimental: Schedule B (lenalidomide, rituximab) Participants receive lenalidomide PO on days 2-22 and rituximab IV over 4-8 hours on days 1, 8, 15, and 22 of course 1 and on day 1 of all subsequent courses. Courses repeat every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. |
Drug: Lenalidomide
Given PO
Other Names:
Biological: Rituximab
Given IV
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Best Overall Disease Response [At the end of 3 courses (84 days)]
Will be monitored simultaneously for each of the subgroups separately using the Bayesian approach of Thall, Simon, Estey. Summary statistics will be provided for continuous variables. Frequency tables will be used to summarize categorical variables. Logistic regression will be will be utilized to assess the effect of patient prognostic factors on the response rate.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Understand and voluntarily sign an informed consent form.
-
Age >/= 18 at the time of signing the informed consent form.
-
Able to adhere to the study visit schedule and other protocol requirements.
-
Untreated indolent non-Hodgkin's lymphoma stage III-IV including small lymphocytic lymphoma, marginal zone lymphoma, grade 1 or 2 follicular lymphoma. (prior radiation for localized disease allowed).
-
At least one measurable lesion according to the International workshop standardized response criteria for non-Hodgkin's lymphomas (IWG) greater than 1.5cm.
-
ECOG performance status of </= 2 at study entry.
-
Laboratory test results within these ranges: Absolute neutrophil count >/= 1.5 x 109/L; Platelet count >/=100 x 109/L; Serum creatinine </= 2.0 mg/dL; Total bilirubin </=1.5 mg/dL; AST (SGOT) and ALT (SGPT) </=2 x ULN or </=5 x ULN if hepatic metastases are present.
-
Disease free of prior malignancies for >/= 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix or breast, or localized prostate cancer treated with curative intent.
-
All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
-
Females of childbearing potential (FCBP) must have a negative serum or urine 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.
-
For patients with bulky disease (tumors >5cm) must be able to take aspirin (81 mg or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin.
Exclusion Criteria:
-
Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
-
Pregnant or breast feeding females.
-
Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
-
Use of any chemotherapy or experimental therapy within 28 days of enrollment.
-
Known hypersensitivity to thalidomide.
-
The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
-
Any prior use of lenalidomide.
-
Concurrent use of other anti-cancer agents or experimental treatments.
-
Known positive for HIV or infectious hepatitis type B or C. (Hepatitis B core antibody can be positive if Hep B surface antigen is negative and no HBV DNA in blood, indicating a cleared infection.)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | M D Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- M.D. Anderson Cancer Center
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Felipe Samaniego, MD, M.D. Anderson Cancer Center
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- 2008-0042
- NCI-2018-01853
- 2008-0042
Study Results
Participant Flow
| Recruitment Details | Recruitment period from time of protocol activation 06/10/2008 to protocol closure to new patient entry 02/04/2013. |
|---|---|
| Pre-assignment Detail | 156 patients were enrolled to participant: 2 patients were deemed histologically ineligible, 79 patients had follicular lymphoma, 31 patients had marginal zone lymphoma, and 44 patients had small lymphocytic lymphoma. |
| Arm/Group Title | Other Histology | Follicular Lymphoma | Marginal Zone Lymphoma | Small Lymphocytic Lymphoma |
|---|---|---|---|---|
| Arm/Group Description | Other Histology | Follicular Lymphoma | Marginal Zone Lymphoma | Small Lymphocytic Lymphoma |
| Period Title: Overall Study | ||||
| STARTED | 2 | 79 | 31 | 44 |
| COMPLETED | 1 | 67 | 23 | 36 |
| NOT COMPLETED | 1 | 12 | 8 | 8 |
Baseline Characteristics
| Arm/Group Title | Other Histology | Follicular Lymphoma | Marginal Zone Lymphoma | Small Lymphocytic Lymphoma | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Other Histology | Follicular Lymphoma | Marginal Zone Lymphoma | Small Lymphocytic Lymphoma | Total of all reporting groups |
| Overall Participants | 2 | 79 | 31 | 44 | 156 |
| Age (Count of Participants) | |||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
1
50%
|
62
78.5%
|
24
77.4%
|
36
81.8%
|
123
78.8%
|
| >=65 years |
1
50%
|
17
21.5%
|
7
22.6%
|
8
18.2%
|
33
21.2%
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
0
0%
|
39
49.4%
|
18
58.1%
|
18
40.9%
|
75
48.1%
|
| Male |
2
100%
|
40
50.6%
|
13
41.9%
|
26
59.1%
|
81
51.9%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
0
0%
|
4
5.1%
|
6
19.4%
|
4
9.1%
|
14
9%
|
| Not Hispanic or Latino |
2
100%
|
54
68.4%
|
20
64.5%
|
30
68.2%
|
106
67.9%
|
| Unknown or Not Reported |
0
0%
|
21
26.6%
|
5
16.1%
|
10
22.7%
|
36
23.1%
|
| Race (NIH/OMB) (Count of Participants) | |||||
| American Indian or Alaska Native |
0
0%
|
1
1.3%
|
0
0%
|
0
0%
|
1
0.6%
|
| Asian |
0
0%
|
1
1.3%
|
1
3.2%
|
0
0%
|
2
1.3%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
2
6.5%
|
4
9.1%
|
6
3.8%
|
| White |
2
100%
|
72
91.1%
|
23
74.2%
|
35
79.5%
|
132
84.6%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
5
6.3%
|
5
16.1%
|
5
11.4%
|
15
9.6%
|
| Region of Enrollment (participants) [Number] | |||||
| United States |
2
100%
|
77
97.5%
|
31
100%
|
44
100%
|
154
98.7%
|
| United Arab Emirates |
0
0%
|
2
2.5%
|
0
0%
|
0
0%
|
2
1.3%
|
| Lymphoma - Non-Hodgkin Stages (Count of Participants) | |||||
| Stage I |
0
0%
|
0
0%
|
1
3.2%
|
0
0%
|
1
0.6%
|
| Stage III |
0
0%
|
35
44.3%
|
9
29%
|
2
4.5%
|
46
29.5%
|
| Stage IV |
2
100%
|
44
55.7%
|
21
67.7%
|
42
95.5%
|
109
69.9%
|
| Bone Marrow Involvement (+) (Count of Participants) | |||||
| Count of Participants [Participants] |
2
100%
|
35
44.3%
|
9
29%
|
2
4.5%
|
48
30.8%
|
| Splenomegaly (+) (Count of Participants) | |||||
| Count of Participants [Participants] |
1
50%
|
6
7.6%
|
5
16.1%
|
7
15.9%
|
19
12.2%
|
| Participants with B Symptoms (+) (Count of Participants) | |||||
| Count of Participants [Participants] |
1
50%
|
10
12.7%
|
3
9.7%
|
7
15.9%
|
21
13.5%
|
Outcome Measures
| Title | Number of Participants With Best Overall Disease Response |
|---|---|
| Description | Will be monitored simultaneously for each of the subgroups separately using the Bayesian approach of Thall, Simon, Estey. Summary statistics will be provided for continuous variables. Frequency tables will be used to summarize categorical variables. Logistic regression will be will be utilized to assess the effect of patient prognostic factors on the response rate. |
| Time Frame | At the end of 3 courses (84 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Other Histology | Follicular Lymphoma | Marginal Zone Lymphoma | Small Lymphocytic Lymphoma |
|---|---|---|---|---|
| Arm/Group Description | Other Histology | Follicular Lymphoma | Marginal Zone Lymphoma | Small Lymphocytic Lymphoma |
| Measure Participants | 2 | 79 | 31 | 44 |
| Best Overall Response - CR |
0
0%
|
56
70.9%
|
17
54.8%
|
8
18.2%
|
| Best Overall Response - CRu Response |
0
0%
|
13
16.5%
|
2
6.5%
|
5
11.4%
|
| Best Overall Response - PR |
1
50%
|
6
7.6%
|
4
12.9%
|
21
47.7%
|
| Best Overall Response - SD |
0
0%
|
1
1.3%
|
3
9.7%
|
3
6.8%
|
| Best Overall Response - PD |
0
0%
|
0
0%
|
1
3.2%
|
6
13.6%
|
| Best Overall Response - Inevaluable |
1
50%
|
3
3.8%
|
4
12.9%
|
1
2.3%
|
Adverse Events
| Time Frame | beginning at the start of intervention and through 30 days post intervention completion, up to 366 days | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Other Histology | Follicular Lymphoma | Marginal Zone Lymphoma | Small Lymphocytic Lymphoma | ||||
| Arm/Group Description | Other Histology | Follicular Lymphoma | Marginal Zone Lymphoma | Small Lymphocytic Lymphoma | ||||
All Cause Mortality |
||||||||
| Other Histology | Follicular Lymphoma | Marginal Zone Lymphoma | Small Lymphocytic Lymphoma | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/2 (0%) | 0/79 (0%) | 0/31 (0%) | 0/44 (0%) | ||||
Serious Adverse Events |
||||||||
| Other Histology | Follicular Lymphoma | Marginal Zone Lymphoma | Small Lymphocytic Lymphoma | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/2 (50%) | 8/79 (10.1%) | 4/31 (12.9%) | 12/44 (27.3%) | ||||
| Cardiac disorders | ||||||||
| Cardiac General (Other) | 0/2 (0%) | 2/79 (2.5%) | 0/31 (0%) | 2/44 (4.5%) | ||||
| General disorders | ||||||||
| Cytokine Release | 1/2 (50%) | 1/79 (1.3%) | 1/31 (3.2%) | 0/44 (0%) | ||||
| Pain | 0/2 (0%) | 0/79 (0%) | 1/31 (3.2%) | 0/44 (0%) | ||||
| Infections and infestations | ||||||||
| Infection | 0/2 (0%) | 0/79 (0%) | 0/31 (0%) | 1/44 (2.3%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Secondary Malignancy | 0/2 (0%) | 8/79 (10.1%) | 1/31 (3.2%) | 0/44 (0%) | ||||
| Nervous system disorders | ||||||||
| Dizziness | 0/2 (0%) | 1/79 (1.3%) | 0/31 (0%) | 1/44 (2.3%) | ||||
| Ischemia cardiovascular | 0/2 (0%) | 0/79 (0%) | 0/31 (0%) | 1/44 (2.3%) | ||||
| Memory Loss | 0/2 (0%) | 0/79 (0%) | 0/31 (0%) | 1/44 (2.3%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Bronchitis | 0/2 (0%) | 0/79 (0%) | 0/31 (0%) | 1/44 (2.3%) | ||||
| Dyspnea | 0/2 (0%) | 0/79 (0%) | 0/31 (0%) | 1/44 (2.3%) | ||||
| Pleural Effusion | 0/2 (0%) | 1/79 (1.3%) | 0/31 (0%) | 0/44 (0%) | ||||
| Pneumonia | 0/2 (0%) | 0/79 (0%) | 1/31 (3.2%) | 0/44 (0%) | ||||
| Pulmonary (Other) | 0/2 (0%) | 2/79 (2.5%) | 0/31 (0%) | 1/44 (2.3%) | ||||
| Vascular disorders | ||||||||
| Thrombosis | 0/2 (0%) | 1/79 (1.3%) | 0/31 (0%) | 3/44 (6.8%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Other Histology | Follicular Lymphoma | Marginal Zone Lymphoma | Small Lymphocytic Lymphoma | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/2 (0%) | 0/79 (0%) | 0/31 (0%) | 0/44 (0%) | ||||
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Felipe Samaniego,MD/Professor, Lymphoma-Myeloma |
|---|---|
| Organization | UT MD Anderson Cancer Center |
| Phone | (713) 745-6824 |
| fsamaniego@mdanderson.org |
- 2008-0042
- NCI-2018-01853
- 2008-0042