Combination Chemotherapy and Lenalidomide in Treating Patients With Newly Diagnosed Stage II-IV Peripheral T-cell Non-Hodgkin's Lymphoma
Study Details
Study Description
Brief Summary
This phase I/II trial studies the side effects and best dose of lenalidomide when given together with combination chemotherapy and to see how well they work in treating patients with newly diagnosed stage II-IV peripheral T-cell non-Hodgkin's lymphoma. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Lenalidomide may stop the growth of peripheral T-cell non-Hodgkin's lymphoma by blocking the growth of new blood vessels necessary for cancer growth. Giving combination chemotherapy with lenalidomide may be a better treatment for peripheral T-cell non-Hodgkin's lymphoma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
|
Phase 1/Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
-
To assess the safety and efficacy of lenalidomide in combination with standard induction therapy (CHOEP- cyclophosphamide, doxorubicin [doxorubicin hydrochloride], etoposide, vincristine [vincristine sulfate] and prednisone) in patients with newly diagnosed stage II, III and IV peripheral T-cell lymphoma not otherwise specified (NOS), anaplastic large cell lymphoma (anaplastic lymphoma receptor tyrosine kinase [ALK] negative) (ALK positive if International Prognostic Index [IPI] 3, 4, or 5), angioimmunoblastic T-cell lymphoma, enteropathy associated T-cell lymphoma or hepatosplenic gamma delta T-cell lymphoma.
-
To establish the maximum tolerated dose of lenalidomide in combination with CHOEP chemotherapy. (Phase I) III. To assess the efficacy (complete response rate) of this combination. (Phase II)
SECONDARY OBJECTIVES:
-
To evaluate overall response rate (complete response [CR] + partial response [PR]) of the combination of lenalidomide and CHOEP chemotherapy.
-
To evaluate the safety and tolerability of the regimen. III. To assess the 2 year progression free survival (PFS) and overall survival (OS) using this regimen.
OUTLINE: This is a phase I, dose-escalation study of lenalidomide, followed by a phase II study.
Patients receive cyclophosphamide intravenously (IV), doxorubicin hydrochloride IV and vincristine sulfate IV on day 1, etoposide IV over 30-60 minutes on days 1-3, prednisone orally (PO) on days 1-5, and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients responding after 6 courses of treatment may then undergo an autologous stem cell transplant or receive maintenance lenalidomide at the discretion of the physician or patient choice as follows:
TRANSPLANT: Patients undergo autologous stem cell transplant per standard of care.
MAINTENANCE LENALIDOMIDE: Patients receive lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment (combination chemotherapy, lenalidomide) Patients receive cyclophosphamide IV, doxorubicin hydrochloride IV and vincristine sulfate IV on day 1, etoposide IV over 30-60 minutes on days 1-3, prednisone PO on days 1-5, and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients responding after 6 courses of treatment may then undergo an autologous stem cell transplant or receive maintenance lenalidomide at the discretion of the physician or patient choice as follows: TRANSPLANT: Patients undergo autologous stem cell transplant per standard of care. MAINTENANCE LENALIDOMIDE: Patients receive lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. |
Procedure: Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous stem cell transplant
Other Names:
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
Drug: Etoposide
Given IV
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Lenalidomide
Given PO
Other Names:
Procedure: Peripheral Blood Stem Cell Transplantation
Undergo peripheral blood stem cell transplant
Other Names:
Drug: Prednisone
Given PO
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Maximum Tolerated Dose (MTD) of Lenalidomide and CHOEP [21 days]
MTD is defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) (Phase I) within the first cycle of study treatment.
- Number of Participants With Adverse Events Graded According to Common Toxicity Criteria (CTC) (Phase I) [Up to 6 cycles of treatment (approximately 5 months)]
Non-hematologic toxicities will be evaluated via the ordinal CTC standard toxicity grading. Hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via CTC standard toxicity grading. Overall toxicity incidence as well as toxicity profiles by dose level and patient will be explored and summarized.
- Complete Response Rate (Phase II) [Up to the completion of course 6 (18 weeks)]
A success is defined to be an objective status of CR after completion of 6 cycles of treatment. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. A 95% confidence interval for the true overall CR rate will be calculated according to the method of Duffy and Santner.
- Overall Response Rate [Up to the completion of course 6 (18 weeks)]
The ORR will be estimated by the total number of patients who achieve a PR or CR at the end of six cycles of treatment divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true ORR will be calculated.
Secondary Outcome Measures
- Number of Participants With Adverse Events Graded According to CTC (Phase II) [Up to 1 year]
The toxicity profile will be further assessed based on phase II patients. Overall toxicity incidence of maximum tolerated dose level of the Intent to treat (ITT) group of subjects is summarized. 39 subjects were dosed with 10 mg dose of Lenalidamide as the ITT group.
- Overall Survival [Time from registration to death due to any cause, assessed up to 1 year]
The distribution of overall survival will be estimated using the method of Kaplan-Meier.
- Progression-free Survival [Time from registration to progression or death due to any cause, assessed up to 2 years]
The distribution of PFS will be estimated using the method of Kaplan-Meier. The PFS rate at 2 years will be estimated. A 2-year PFS rate of 60% will be considered of interest.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically confirmed new diagnosis of stage II, III and IV peripheral T-cell non-Hodgkin's lymphoma not otherwise specified (NOS), anaplastic large cell lymphoma (ALK negative) (ALK positive if IPI 3, 4, or 5), angioimmunoblastic T-cell lymphoma, enteropathy associated T-cell lymphoma, hepatosplenic gamma delta T-cell lymphoma
-
Pathology material: hematoxylin and eosin (H&E) stain and immunohistochemistry (IHC) slides or a representative formalin-fixed paraffin-embedded (FFPE) tissue block along with the pathology report from initial diagnosis, should be sent to be reviewed, and the diagnosis confirmed by Mayo Clinic department (retrospective diagnostic review: treatment may commence prior to the Mayo Clinic review)
-
No prior therapy with the exception of prior radiation therapy and/or prednisone alone, at the discretion of the investigator based on current diagnosis and clinical condition; this prednisone treatment will not count toward the 6 cycles of treatment given in the study
-
Expected survival duration of > 3 months
-
Karnofsky performance status > 70
-
Absolute neutrophil count (ANC) > 1000 cells/mm^3, unless cytopenias due to non-Hodgkin lymphoma (NHL) (i.e., bone marrow involvement or splenomegaly)
-
Platelet count > 100,000/uL or > 75,000/uL if bone marrow (BM) involvement or splenomegaly
-
Total bilirubin =< 1.5 x upper normal limit, or =< 3 x upper normal limit if documented hepatic involvement with lymphoma, or =< 5 x upper normal limit if history of Gilbert's disease
-
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper normal limit (=< 5 x upper normal limit if documented hepatic involvement with lymphoma)
-
Serum creatinine < 2.0 mg/dL or calculated creatinine clearance (CrCl) > 45 mL/min (Cockcroft-Gault)
-
Prothrombin time (PT) or international normalized ratio (INR), and partial thromboplastin time (PTT) =< 1.5 x upper limit of normal unless patient is receiving anticoagulants; if patient is on warfarin therapy, levels should be within therapeutic range
-
If currently not on anticoagulation medication, willing and able to take aspirin (81 or 325 mg) daily; if aspirin is contraindicated, the patient may be considered for the study if on therapeutic dose warfarin or low molecular weight heparin; patients unable to take any prophylaxis are not eligible
-
Patients with measurable disease; patients with non-measurable but evaluable disease may be eligible after discussion with the principal investigator (PI); baseline measurements and evaluations must be obtained within 6 weeks of registration to the study; abnormal positron emission tomography (PET)/computed tomography (CT) scans will not constitute evaluable disease, unless verified by CT scan or other appropriate imaging
-
Patients with measurable disease must have at least one objective measurable disease parameter; a clearly defined, bi-dimensionally measurable defect or mass measuring at least 1.5 cm in diameter on the CT portion of a PET/CT or CT scan or magnetic resonance imaging (MRI) (if appropriate) will constitute measurable disease; proof of lymphoma in the liver is required by a confirmation biopsy; skin lesions can be used as measurable disease provided bi-dimensional measurements are possible
-
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 the REMS program
-
Women must not be pregnant or breast-feeding
-
Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS program
-
All females of childbearing potential must have a blood test within 2 weeks prior to registration to rule out pregnancy
-
Pregnancy testing is not required for post-menopausal or surgically sterilized women
-
Male and female patients of reproductive potential must agree follow accepted birth control measures
-
Patient must be able to adhere to the study visit schedule and other protocol requirements
-
Patients must be willing to give written informed consent, and sign an institutionally approved consent form before performance of any study-related procedure not part of normal medical care as noted above; with the exception of 1 cycle of chemotherapy based on current diagnosis and clinical condition, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
-
No serious disease or condition that, in the opinion of the investigator, would compromise the patient's ability to participate in the study
Exclusion Criteria:
-
Pregnant or breast feeding females
-
Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); patients who are seropositive ( i.e. hepatitis B core antibody positive; quantitative deoxyribonucleic acid [DNA] negative) are eligible with appropriate prophylaxis
-
Major surgery within 2 weeks of study drug administration
-
Prior malignancies within the past 3 years with exception of adequately treated basal cell, squamous cell skin cancer, or thyroid cancer; carcinoma in situ of the cervix or breast; prostate cancer of Gleason grade 6 or less with stable prostate-specific antigen (PSA) levels
-
Patients with a diagnosis of other peripheral T-cell lymphoma (PTCL) histologies other than those specified in the inclusion criteria
-
Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, or antiviral drugs
-
Any other clinically significant medical disease or condition laboratory abnormality or psychiatric illness that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent
-
Known hypersensitivity to thalidomide or lenalidomide
-
The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide, lenalidomide or similar drugs
-
Ejection fraction of < 45% by either multi gated acquisition scan (MUGA) or echocardiogram (ECHO)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | City of Hope Comprehensive Cancer Center | Duarte | California | United States | 91010 |
| 2 | Stanford Cancer Institute | Palo Alto | California | United States | 94304 |
| 3 | University of Colorado Cancer Center - Anschutz Cancer Pavilion | Aurora | Colorado | United States | 80045 |
| 4 | Emory University/Winship Cancer Institute | Atlanta | Georgia | United States | 30322 |
| 5 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
| 6 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 7 | University of Nebraska Medical Center | Omaha | Nebraska | United States | 68198 |
| 8 | Memorial Sloan-Kettering Cancer Center | New York | New York | United States | 10065 |
Sponsors and Collaborators
- University of Nebraska
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Matthew Lunning, University of Nebraska
Study Documents (Full-Text)
More Information
Publications
None provided.- 511-14
- NCI-2015-00088
- RV-CL-PTCL-PI-003858
- 511-14
- P30CA036727
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Per the protocol, date of enrollment is defined as the date of consent. For this study 54 participants were consented. 10 were determined to be ineligible and not assigned to a study group. |
| Arm/Group Title | 10 mg Lenalidomide Participants | 15 mg Lenalidomide Participants |
|---|---|---|
| Arm/Group Description | Patients receive cyclophosphamide IV, doxorubicin hydrochloride IV and vincristine sulfate IV on day 1, etoposide IV over 30-60 minutes on days 1-3, prednisone PO on days 1-5, and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients responding after 6 courses of treatment may then undergo an autologous stem cell transplant or receive maintenance lenalidomide at the discretion of the physician or patient choice as follows: TRANSPLANT: Patients undergo autologous stem cell transplant per standard of care. MAINTENANCE LENALIDOMIDE: Patients receive lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous stem cell transplant | Patients receive cyclophosphamide IV, doxorubicin hydrochloride IV and vincristine sulfate IV on day 1, etoposide IV over 30-60 minutes on days 1-3, prednisone PO on days 1-5, and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients responding after 6 courses of treatment may then undergo an autologous stem cell transplant or receive maintenance lenalidomide at the discretion of the physician or patient choice as follows: TRANSPLANT: Patients undergo autologous stem cell transplant per standard of care. MAINTENANCE LENALIDOMIDE: Patients receive lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous stem cell transplant |
| Period Title: Overall Study | ||
| STARTED | 40 | 4 |
| COMPLETED | 39 | 4 |
| NOT COMPLETED | 1 | 0 |
Baseline Characteristics
| Arm/Group Title | 10 mg Lenalidomide Participants | 15 mg Lenalidomide Participants | Total |
|---|---|---|---|
| Arm/Group Description | Patients receive cyclophosphamide IV, doxorubicin hydrochloride IV and vincristine sulfate IV on day 1, etoposide IV over 30-60 minutes on days 1-3, prednisone PO on days 1-5, and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients responding after 6 courses of treatment may then undergo an autologous stem cell transplant or receive maintenance lenalidomide at the discretion of the physician or patient choice as follows: TRANSPLANT: Patients undergo autologous stem cell transplant per standard of care. MAINTENANCE LENALIDOMIDE: Patients receive lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous stem cell transplant | Patients receive cyclophosphamide IV, doxorubicin hydrochloride IV and vincristine sulfate IV on day 1, etoposide IV over 30-60 minutes on days 1-3, prednisone PO on days 1-5, and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients responding after 6 courses of treatment may then undergo an autologous stem cell transplant or receive maintenance lenalidomide at the discretion of the physician or patient choice as follows: TRANSPLANT: Patients undergo autologous stem cell transplant per standard of care. MAINTENANCE LENALIDOMIDE: Patients receive lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous stem cell transplant | Total of all reporting groups |
| Overall Participants | 39 | 4 | 43 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
58
(13)
|
62
(4)
|
58
(13)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
19
48.7%
|
2
50%
|
21
48.8%
|
| Male |
20
51.3%
|
2
50%
|
22
51.2%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
3
7.7%
|
0
0%
|
3
7%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
2
5.1%
|
2
50%
|
4
9.3%
|
| White |
30
76.9%
|
2
50%
|
32
74.4%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
4
10.3%
|
0
0%
|
4
9.3%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
39
100%
|
4
100%
|
43
100%
|
Outcome Measures
| Title | Maximum Tolerated Dose (MTD) of Lenalidomide and CHOEP |
|---|---|
| Description | MTD is defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) (Phase I) within the first cycle of study treatment. |
| Time Frame | 21 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Eight subjects were dosed at 10 mg dose and 4 subjects were dosed at 15 mg dose. |
| Arm/Group Title | Treatment (Combination Chemotherapy, Lenalidomide) |
|---|---|
| Arm/Group Description | Patients receive cyclophosphamide IV, doxorubicin hydrochloride IV and vincristine sulfate IV on day 1, etoposide IV over 30-60 minutes on days 1-3, prednisone PO on days 1-5, and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients responding after 6 courses of treatment may then undergo an autologous stem cell transplant or receive maintenance lenalidomide at the discretion of the physician or patient choice as follows: TRANSPLANT: Patients undergo autologous stem cell transplant per standard of care. MAINTENANCE LENALIDOMIDE: Patients receive lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous stem cell transplant |
| Measure Participants | 12 |
| Number [milligrams] |
10
|
| Title | Number of Participants With Adverse Events Graded According to Common Toxicity Criteria (CTC) (Phase I) |
|---|---|
| Description | Non-hematologic toxicities will be evaluated via the ordinal CTC standard toxicity grading. Hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via CTC standard toxicity grading. Overall toxicity incidence as well as toxicity profiles by dose level and patient will be explored and summarized. |
| Time Frame | Up to 6 cycles of treatment (approximately 5 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Toxicity was measured for all subjects dosed during Phase 1 of the study. 10 mg and 15 mg dose levels. |
| Arm/Group Title | 10 mg Lenalidomide Participants | 15 mg Lenalidomide Participants |
|---|---|---|
| Arm/Group Description | Patients receive cyclophosphamide IV, doxorubicin hydrochloride IV and vincristine sulfate IV on day 1, etoposide IV over 30-60 minutes on days 1-3, prednisone PO on days 1-5, and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients responding after 6 courses of treatment may then undergo an autologous stem cell transplant or receive maintenance lenalidomide at the discretion of the physician or patient choice as follows: TRANSPLANT: Patients undergo autologous stem cell transplant per standard of care. MAINTENANCE LENALIDOMIDE: Patients receive lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. | Patients receive cyclophosphamide IV, doxorubicin hydrochloride IV and vincristine sulfate IV on day 1, etoposide IV over 30-60 minutes on days 1-3, prednisone PO on days 1-5, and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients responding after 6 courses of treatment may then undergo an autologous stem cell transplant or receive maintenance lenalidomide at the discretion of the physician or patient choice as follows: TRANSPLANT: Patients undergo autologous stem cell transplant per standard of care. MAINTENANCE LENALIDOMIDE: Patients receive lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. |
| Measure Participants | 8 | 4 |
| grade 3,4 neutropenia |
5
12.8%
|
4
100%
|
| grade 3, 4 anemia |
3
7.7%
|
3
75%
|
| grade 3, 4 thrombocytopenia |
2
5.1%
|
3
75%
|
| grade 3,4 neutropenia fever |
4
10.3%
|
0
0%
|
| grade 3, 4 diarrhea |
0
0%
|
2
50%
|
| grade 3, 4 hyperglycemia |
0
0%
|
2
50%
|
| grade 3, 4 hypokalemia |
0
0%
|
1
25%
|
| grade 3, 4 hypotension |
0
0%
|
1
25%
|
| grade 3, 4 hyperbilirubinemia |
0
0%
|
1
25%
|
| grade 3, 4 mucositis |
0
0%
|
2
50%
|
| grade 3,4 nausea |
0
0%
|
2
50%
|
| grade 3,4 vomiting |
0
0%
|
1
25%
|
| Title | Complete Response Rate (Phase II) |
|---|---|
| Description | A success is defined to be an objective status of CR after completion of 6 cycles of treatment. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. A 95% confidence interval for the true overall CR rate will be calculated according to the method of Duffy and Santner. |
| Time Frame | Up to the completion of course 6 (18 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Assessment based on phase II patients given the maximum tolerated dose level (10 mg) as the Intent to treat (ITT) group of subjects. 39 subjects were dosed with 10 mg dose of Lenalidamide as the ITT group. |
| Arm/Group Title | Treatment (Combination Chemotherapy, Lenalidomide) |
|---|---|
| Arm/Group Description | Patients receive cyclophosphamide IV, doxorubicin hydrochloride IV and vincristine sulfate IV on day 1, etoposide IV over 30-60 minutes on days 1-3, prednisone PO on days 1-5, and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients responding after 6 courses of treatment may then undergo an autologous stem cell transplant or receive maintenance lenalidomide at the discretion of the physician or patient choice as follows: TRANSPLANT: Patients undergo autologous stem cell transplant per standard of care. MAINTENANCE LENALIDOMIDE: Patients receive lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous stem cell transplant Cyclophosphamide: Given IV Doxorubicin Hydrochloride: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO Peripheral Blood Stem Cell Transplantation: Undergo peripheral blood stem cell transplant Prednisone: Given PO Vincristine Sulfate: Given IV |
| Measure Participants | 39 |
| Number (95% Confidence Interval) [percentage of participants] |
49
125.6%
|
| Title | Overall Response Rate |
|---|---|
| Description | The ORR will be estimated by the total number of patients who achieve a PR or CR at the end of six cycles of treatment divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true ORR will be calculated. |
| Time Frame | Up to the completion of course 6 (18 weeks) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Assessment based on phase II patients given the maximum tolerated dose level (10 mg) as the Intent to treat (ITT) group of subjects. 39 subjects were dosed with 10 mg dose of Lenalidamide as the ITT group. |
| Arm/Group Title | Treatment (Combination Chemotherapy, Lenalidomide) |
|---|---|
| Arm/Group Description | Patients receive cyclophosphamide IV, doxorubicin hydrochloride IV and vincristine sulfate IV on day 1, etoposide IV over 30-60 minutes on days 1-3, prednisone PO on days 1-5, and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients responding after 6 courses of treatment may then undergo an autologous stem cell transplant or receive maintenance lenalidomide at the discretion of the physician or patient choice as follows: TRANSPLANT: Patients undergo autologous stem cell transplant per standard of care. MAINTENANCE LENALIDOMIDE: Patients receive lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous stem cell transplant Cyclophosphamide: Given IV Doxorubicin Hydrochloride: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO Peripheral Blood Stem Cell Transplantation: Undergo peripheral blood stem cell transplant Prednisone: Given PO Vincristine Sulfate: Given IV |
| Measure Participants | 39 |
| Number (95% Confidence Interval) [percentage of participants] |
69
176.9%
|
| Title | Number of Participants With Adverse Events Graded According to CTC (Phase II) |
|---|---|
| Description | The toxicity profile will be further assessed based on phase II patients. Overall toxicity incidence of maximum tolerated dose level of the Intent to treat (ITT) group of subjects is summarized. 39 subjects were dosed with 10 mg dose of Lenalidamide as the ITT group. |
| Time Frame | Up to 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety data for the Intent to treat (ITT) group of subjects. |
| Arm/Group Title | Treatment (Combination Chemotherapy, Lenalidomide) |
|---|---|
| Arm/Group Description | Patients receive cyclophosphamide IV, doxorubicin hydrochloride IV and vincristine sulfate IV on day 1, etoposide IV over 30-60 minutes on days 1-3, prednisone PO on days 1-5, and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients responding after 6 courses of treatment may then undergo an autologous stem cell transplant or receive maintenance lenalidomide at the discretion of the physician or patient choice as follows: TRANSPLANT: Patients undergo autologous stem cell transplant per standard of care. MAINTENANCE LENALIDOMIDE: Patients receive lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous stem cell transplant |
| Measure Participants | 39 |
| grade 3,4 neutropenia |
27
69.2%
|
| grade 3, 4 leukopenia |
25
64.1%
|
| grade 3, 4 anemia |
17
43.6%
|
| grade 3, 4 thrombocytopenia |
17
43.6%
|
| grade 3, 4 lymphopenia |
18
46.2%
|
| grade 3, 4 febrile neutropenia |
15
38.5%
|
| grade 3, 4 diarrhea |
3
7.7%
|
| grade 3, 4 Peripheral sensory neuropathy |
2
5.1%
|
| grade 3, 4 fatigue |
1
2.6%
|
| grade 3, 4 nausea |
1
2.6%
|
| grade 3, 4 anorexia |
1
2.6%
|
| grade 3, 4 vomiting |
1
2.6%
|
| grade 3, 4 mucositis oral |
1
2.6%
|
| grade 3, 4 Rash maculo-papular |
1
2.6%
|
| grade 3, 4 hypotension |
1
2.6%
|
| grade 3, 4 back pain |
1
2.6%
|
| Title | Overall Survival |
|---|---|
| Description | The distribution of overall survival will be estimated using the method of Kaplan-Meier. |
| Time Frame | Time from registration to death due to any cause, assessed up to 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| Assessment based on phase II patients given the maximum tolerated dose level (10 mg) as the Intent to treat (ITT) group of subjects. 39 subjects were dosed with 10 mg dose of Lenalidamide as the ITT group. |
| Arm/Group Title | Treatment (Combination Chemotherapy, Lenalidomide) |
|---|---|
| Arm/Group Description | Patients receive cyclophosphamide IV, doxorubicin hydrochloride IV and vincristine sulfate IV on day 1, etoposide IV over 30-60 minutes on days 1-3, prednisone PO on days 1-5, and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients responding after 6 courses of treatment may then undergo an autologous stem cell transplant or receive maintenance lenalidomide at the discretion of the physician or patient choice as follows: TRANSPLANT: Patients undergo autologous stem cell transplant per standard of care. MAINTENANCE LENALIDOMIDE: Patients receive lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous stem cell transplant |
| Measure Participants | 39 |
| Number (95% Confidence Interval) [percentage of participants] |
89
228.2%
|
| Title | Progression-free Survival |
|---|---|
| Description | The distribution of PFS will be estimated using the method of Kaplan-Meier. The PFS rate at 2 years will be estimated. A 2-year PFS rate of 60% will be considered of interest. |
| Time Frame | Time from registration to progression or death due to any cause, assessed up to 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Assessment based on phase II patients given the maximum tolerated dose level (10 mg) as the Intent to treat (ITT) group of subjects. 39 subjects were dosed with 10 mg dose of Lenalidamide as the ITT group. |
| Arm/Group Title | Treatment (Combination Chemotherapy, Lenalidomide) |
|---|---|
| Arm/Group Description | Patients receive cyclophosphamide IV, doxorubicin hydrochloride IV and vincristine sulfate IV on day 1, etoposide IV over 30-60 minutes on days 1-3, prednisone PO on days 1-5, and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients responding after 6 courses of treatment may then undergo an autologous stem cell transplant or receive maintenance lenalidomide at the discretion of the physician or patient choice as follows: TRANSPLANT: Patients undergo autologous stem cell transplant per standard of care. MAINTENANCE LENALIDOMIDE: Patients receive lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous stem cell transplant Cyclophosphamide: Given IV Doxorubicin Hydrochloride: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO Peripheral Blood Stem Cell Transplantation: Undergo peripheral blood stem cell transplant Prednisone: Given PO Vincristine Sulfate: Given IV |
| Measure Participants | 39 |
| Number (95% Confidence Interval) [percentage of participants] |
55
141%
|
Adverse Events
| Time Frame | Adverse events were collected from time of consent until 30 days post after the last administration of study drug (lenalidomide). For subjects going on to transplant after Len-CHOEP treatment this was approximately 5 months. For subjects going on the the maintenance len treatment instead of transplant upto an additional 1 year of maintenance lenalidomide treatment was allowed. (17 months total) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Treatment (10 mg Lenalidomide) | Treatment (15 mg Lenalidomide) | ||
| Arm/Group Description | Patients receive cyclophosphamide IV, doxorubicin hydrochloride IV and vincristine sulfate IV on day 1, etoposide IV over 30-60 minutes on days 1-3, prednisone PO on days 1-5, and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients responding after 6 courses of treatment may then undergo an autologous stem cell transplant or receive maintenance lenalidomide at the discretion of the physician or patient choice as follows: TRANSPLANT: Patients undergo autologous stem cell transplant per standard of care. MAINTENANCE LENALIDOMIDE: Patients receive lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous stem cell transplant | Patients receive cyclophosphamide IV, doxorubicin hydrochloride IV and vincristine sulfate IV on day 1, etoposide IV over 30-60 minutes on days 1-3, prednisone PO on days 1-5, and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients responding after 6 courses of treatment may then undergo an autologous stem cell transplant or receive maintenance lenalidomide at the discretion of the physician or patient choice as follows: TRANSPLANT: Patients undergo autologous stem cell transplant per standard of care. MAINTENANCE LENALIDOMIDE: Patients receive lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous stem cell transplant | ||
All Cause Mortality |
||||
| Treatment (10 mg Lenalidomide) | Treatment (15 mg Lenalidomide) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/39 (23.1%) | 1/4 (25%) | ||
Serious Adverse Events |
||||
| Treatment (10 mg Lenalidomide) | Treatment (15 mg Lenalidomide) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 14/39 (35.9%) | 2/4 (50%) | ||
| Blood and lymphatic system disorders | ||||
| Febrile neutropenia | 14/39 (35.9%) | 1/4 (25%) | ||
| platelet count decreased | 7/39 (17.9%) | 0/4 (0%) | ||
| Neutrophil count decreased | 5/39 (12.8%) | 1/4 (25%) | ||
| anemia | 5/39 (12.8%) | 0/4 (0%) | ||
| White blood cells decreased | 2/39 (5.1%) | 0/4 (0%) | ||
| Cardiac disorders | ||||
| cardiac arrest | 1/39 (2.6%) | 0/4 (0%) | ||
| Ear and labyrinth disorders | ||||
| hearing impaired | 0/39 (0%) | 1/4 (25%) | ||
| Gastrointestinal disorders | ||||
| diarrhea | 2/39 (5.1%) | 1/4 (25%) | ||
| Abdominal pain | 1/39 (2.6%) | 0/4 (0%) | ||
| colitis | 1/39 (2.6%) | 0/4 (0%) | ||
| Enterocolitis | 1/39 (2.6%) | 0/4 (0%) | ||
| gastric hemorrhage | 1/39 (2.6%) | 0/4 (0%) | ||
| Ileus | 1/39 (2.6%) | 0/4 (0%) | ||
| nausea | 0/39 (0%) | 1/4 (25%) | ||
| vomiting | 0/39 (0%) | 1/4 (25%) | ||
| General disorders | ||||
| fever | 5/39 (12.8%) | 0/4 (0%) | ||
| fatigue | 1/39 (2.6%) | 0/4 (0%) | ||
| gait disturbance | 0/39 (0%) | 1/4 (25%) | ||
| Infections and infestations | ||||
| sepsis | 5/39 (12.8%) | 0/4 (0%) | ||
| Appendicitis | 1/39 (2.6%) | 0/4 (0%) | ||
| Lung infection | 1/39 (2.6%) | 0/4 (0%) | ||
| Investigations | ||||
| Blood bilirubin increased | 1/39 (2.6%) | 0/4 (0%) | ||
| creatinine increased | 1/39 (2.6%) | 0/4 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| back pain | 1/39 (2.6%) | 0/4 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Leukemia secondary to oncology chemotherapy | 1/39 (2.6%) | 0/4 (0%) | ||
| T3 ADRENAL CORTICAL CARCINOMA | 0/39 (0%) | 1/4 (25%) | ||
| Nervous system disorders | ||||
| dizziness | 0/39 (0%) | 1/4 (25%) | ||
| ACUTE ENCEPHALOPATHY | 0/39 (0%) | 1/4 (25%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| pleural effusion | 2/39 (5.1%) | 0/4 (0%) | ||
| dyspnea | 1/39 (2.6%) | 0/4 (0%) | ||
| Vascular disorders | ||||
| hypotension | 2/39 (5.1%) | 0/4 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Treatment (10 mg Lenalidomide) | Treatment (15 mg Lenalidomide) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 32/39 (82.1%) | 4/4 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Anemia | 23/39 (59%) | 3/4 (75%) | ||
| Other blood and lymphatic disorders | 3/39 (7.7%) | 0/4 (0%) | ||
| PANCYTOPENIA | 0/39 (0%) | 1/4 (25%) | ||
| Cardiac disorders | ||||
| sinus tachycardia | 3/39 (7.7%) | 0/4 (0%) | ||
| Ear and labyrinth disorders | ||||
| external ear inflammation | 2/39 (5.1%) | 0/4 (0%) | ||
| Eye disorders | ||||
| dry eye | 3/39 (7.7%) | 0/4 (0%) | ||
| blurred vision | 0/39 (0%) | 1/4 (25%) | ||
| Gastrointestinal disorders | ||||
| Nausea | 17/39 (43.6%) | 2/4 (50%) | ||
| diarrhea | 16/39 (41%) | 2/4 (50%) | ||
| constipation | 13/39 (33.3%) | 1/4 (25%) | ||
| Anorexia | 10/39 (25.6%) | 0/4 (0%) | ||
| mucositis, oral | 10/39 (25.6%) | 2/4 (50%) | ||
| Vomiting | 10/39 (25.6%) | 1/4 (25%) | ||
| Abdominal pain | 6/39 (15.4%) | 0/4 (0%) | ||
| other gastrointestinal disorders | 4/39 (10.3%) | 0/4 (0%) | ||
| dysphagia | 3/39 (7.7%) | 0/4 (0%) | ||
| gastroesophageal reflux disease | 2/39 (5.1%) | 0/4 (0%) | ||
| General disorders | ||||
| Fatigue | 32/39 (82.1%) | 4/4 (100%) | ||
| general disorders -Other | 7/39 (17.9%) | 0/4 (0%) | ||
| chills | 4/39 (10.3%) | 1/4 (25%) | ||
| fever | 4/39 (10.3%) | 1/4 (25%) | ||
| malaise | 4/39 (10.3%) | 0/4 (0%) | ||
| pain | 4/39 (10.3%) | 2/4 (50%) | ||
| edema limbs | 3/39 (7.7%) | 1/4 (25%) | ||
| Infusion related reaction | 3/39 (7.7%) | 0/4 (0%) | ||
| non-cardiac chest pain | 0/39 (0%) | 1/4 (25%) | ||
| Immune system disorders | ||||
| Allergic reaction | 0/39 (0%) | 1/4 (25%) | ||
| Infections and infestations | ||||
| infections and infestation, Other | 8/39 (20.5%) | 1/4 (25%) | ||
| urinary tract infection | 2/39 (5.1%) | 0/4 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| fall | 2/39 (5.1%) | 0/4 (0%) | ||
| Vascular access complication | 0/39 (0%) | 1/4 (25%) | ||
| DRAINAGE FROM BIOPSY SITE | 0/39 (0%) | 1/4 (25%) | ||
| Investigations | ||||
| White blood cell decreased | 26/39 (66.7%) | 3/4 (75%) | ||
| Neutrophil count decreased | 25/39 (64.1%) | 4/4 (100%) | ||
| Lymphocyte count decreased | 20/39 (51.3%) | 4/4 (100%) | ||
| Platelet count decreased | 18/39 (46.2%) | 3/4 (75%) | ||
| weight loss | 5/39 (12.8%) | 0/4 (0%) | ||
| blood bilirubin increased | 2/39 (5.1%) | 1/4 (25%) | ||
| Alkaline phosphatase increased | 0/39 (0%) | 1/4 (25%) | ||
| creatinine increased | 0/39 (0%) | 1/4 (25%) | ||
| Metabolism and nutrition disorders | ||||
| hypoalbuminemia | 3/39 (7.7%) | 1/4 (25%) | ||
| hypokalemia | 3/39 (7.7%) | 1/4 (25%) | ||
| hyponatremia | 3/39 (7.7%) | 1/4 (25%) | ||
| dehydration | 2/39 (5.1%) | 0/4 (0%) | ||
| hyperglycemia | 2/39 (5.1%) | 2/4 (50%) | ||
| hypocalcemia | 2/39 (5.1%) | 1/4 (25%) | ||
| hypophosphatemia | 2/39 (5.1%) | 0/4 (0%) | ||
| hypomagnesemia | 0/39 (0%) | 1/4 (25%) | ||
| hypermagnesemia | 0/39 (0%) | 1/4 (25%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| back pain | 6/39 (15.4%) | 0/4 (0%) | ||
| myalgia | 4/39 (10.3%) | 0/4 (0%) | ||
| neck pain | 4/39 (10.3%) | 0/4 (0%) | ||
| other musculoskeletal and connective tissue disorders | 2/39 (5.1%) | 0/4 (0%) | ||
| Nervous system disorders | ||||
| peripheral sensory neuropathy | 16/39 (41%) | 1/4 (25%) | ||
| dizziness | 11/39 (28.2%) | 0/4 (0%) | ||
| dysgeusia | 5/39 (12.8%) | 2/4 (50%) | ||
| headache | 5/39 (12.8%) | 1/4 (25%) | ||
| syncope | 4/39 (10.3%) | 0/4 (0%) | ||
| other nervous system disorders | 3/39 (7.7%) | 0/4 (0%) | ||
| peripheral motor neuropathy | 2/39 (5.1%) | 0/4 (0%) | ||
| Psychiatric disorders | ||||
| Anxiety | 5/39 (12.8%) | 0/4 (0%) | ||
| insomnia | 2/39 (5.1%) | 0/4 (0%) | ||
| Renal and urinary disorders | ||||
| urinary frequency | 2/39 (5.1%) | 0/4 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| cough | 8/39 (20.5%) | 3/4 (75%) | ||
| dyspnea | 5/39 (12.8%) | 2/4 (50%) | ||
| nasal congestion | 5/39 (12.8%) | 0/4 (0%) | ||
| other respiratory, thoracic and mediastinal disorders | 3/39 (7.7%) | 1/4 (25%) | ||
| sore throat | 3/39 (7.7%) | 0/4 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 23/39 (59%) | 2/4 (50%) | ||
| rash maculo-papular | 9/39 (23.1%) | 1/4 (25%) | ||
| Other skin and subcutaneous tissue disorders | 5/39 (12.8%) | 0/4 (0%) | ||
| pain of skin | 2/39 (5.1%) | 0/4 (0%) | ||
| rash acneiform | 2/39 (5.1%) | 0/4 (0%) | ||
| dry skin | 0/39 (0%) | 1/4 (25%) | ||
| Vascular disorders | ||||
| hypotension | 8/39 (20.5%) | 1/4 (25%) | ||
| hypertension | 2/39 (5.1%) | 0/4 (0%) | ||
| lymphedema | 2/39 (5.1%) | 0/4 (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 | Matthew Lunning, DO |
|---|---|
| Organization | University of Nebraska Medical Center |
| Phone | 402-559-7164 |
| mlunning@unmc.edu |
- 511-14
- NCI-2015-00088
- RV-CL-PTCL-PI-003858
- 511-14
- P30CA036727