Combination Chemotherapy and Pralatrexate as First-Line Therapy in Treating Patients With Non-Hodgkin Lymphoma
Study Details
Study Description
Brief Summary
This phase II trial studies how well combination chemotherapy and pralatrexate works in treating patients with non-Hodgkin lymphoma (NHL). Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
- To evaluate in a Phase II study a preliminary estimate of the complete response (CR) rate of a new chemotherapy regimen involving Cyclophosphamide, Etoposide, Vincristine and Prednisone (CEOP) alternating with Pralatrexate (P) as front line therapy for patients with Stage II, III and IV Peripheral T-Cell NHL not otherwise specified (NOS), Anaplastic large cell lymphoma (ALK negative), Angioimmunoblastic T-cell lymphoma, Enteropathy associated T-cell lymphoma, Hepatosplenic gamma delta T-cell lymphoma followed by an optional stem cell transplant with high dose chemotherapy and Autologous stem cell transplant.
SECONDARY OBJECTIVES:
-
To evaluate partial response (PR). II. To evaluate overall response (CR+PR). III. To evaluate the safety and tolerability of the regimen IV. To assess the 2 year event free survival (EFS) and overall survival (OS) using this regimen.
-
To assess the percentage of patients who proceeded with transplant. VI. To evaluate the ability to collect peripheral blood stem cells after this regimen.
OUTLINE:
Patients receive cyclophosphamide intravenously (IV) and vincristine IV on day 1, etoposide IV on days 1-3 or orally (PO) once daily (QD) on days 2-3, and prednisone PO QD on days 1-5 (CEOP administration). Patients also receive pralatrexate IV over 3-5 minutes on days 15, 22, and 29 (P administration). Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Patients with Complete Response (CR) or Partial Response (PR), per investigators discretion, may then undergo hematopoietic stem cell collection and administration of standard preparative regimen followed by hematopoietic stem cell transplantation.
After completion of study treatment, patients are followed up for 2 years (transplant patients) or periodically.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment "A" Treatment: Cyclophosphamide,Etoposide, Vincristine and Prednisone (CEOP) "B" Treatment: Pralatrexate (P) "A" cycles (CEOP) of the treatment regimen are 14 days, followed by " B" cycles (P) which are 21 days, followed by 7 days of rest for a total of 42 days per course, unless criteria are met for stopping or holding treatment or to a maximum of 6 courses. Patients with Complete Response (CR) or Partial Response (PR), per investigators discretion, may then undergo hematopoietic stem cell collection and administration of standard preparative regimen followed by hematopoietic stem cell transplantation. |
Drug: prednisone
Given PO
Other Names:
Drug: cyclophosphamide
Given IV
Other Names:
Drug: etoposide
Given PO or IV
Other Names:
Drug: Vincristine
Given IV
Other Names:
Drug: pralatrexate
Given IV
Other Names:
Other: laboratory biomarker analysis
Correlative studies
Genetic: comparative genomic hybridization
Correlative studies
Other Names:
Genetic: gene expression analysis
Correlative studies
Genetic: nucleic acid sequencing
Correlative studies
Other Names:
Genetic: mutation analysis
Correlative studies
Other: immunohistochemistry staining method
Correlative studies
Other Names:
Genetic: microarray analysis
Correlative studies
Other Names:
Genetic: RNA analysis
Correlative studies
|
Outcome Measures
Primary Outcome Measures
- Complete Response Rate of Cyclophosphamide, Etoposide, Vincristine and Prednisone (CEOP) and Pralatrexate (P) Treatment [168 days - 252 days (4-6 courses; 42 days per course)]
Complete Response Rate (CR) was reported at the end of the CEOP-P (6 courses for patients not receiving transplant and 4-6 courses for patients receiving transplant). Response assessment was performed by computerized tomography (CT) or positron emission tomography (PET)/CT based on the investigator's preference after cycles 2, 4 and 6. Response was assessed by the treating physician according to the Cheson Revised response criteria (Cheson et al,, 2007) or International Harmonization Project criteria (Cheson, 2007), based on imaging modality used. Complete Response Definition: Disappearance of all evidence of disease Nodal Masses: (a) [18F]fluorodeoxyglucose(FDG)-avid or PET positive prior to therapy; mass of any size permitted if PETnegative (b) Variably FDG-avid or PET negative; regression to normal size on CT Spleen, Liver: Not palpable, nodules disappeared Bone Marrow: Infiltrate cleared on repeat biopsy; if indeterminate by morphology, immunohistochemistry should be negative
Secondary Outcome Measures
- Overall Response Rates (ORR)= (Complete Response Rates (CR) + Partial Response Rates (PR)) [2 years]
Every patient who fulfills all aspects of patient eligibility who receives at least 2 complete courses of chemotherapy will be evaluable for the response endpoint. Response rates will be descriptively summarized using percentages and 95% confidence intervals. Complete Response Definition: Defined in Primary Objective Partial Response Definition: Regression of measurable disease and no new sites, Nodal Masses: > 50% decrease in sum of the product of the diameters (SPD) of up to 6 largest dominant masses; no increase in size of other nodes FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site Variably FDG-avid or PET negative; regression on CT Spleen, Liver:> 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen Bone Marrow: Irrelevant if positive prior to therapy; cell type should be specified
- Event Free Survival (EFS) [2 years]
Estimated 2-year Event Free Survival (EFS), as well as plots of EFS, will be produced using the method of Kaplan-Meier, along with 95% confidence intervals for EFS. Event-free survival is defined as time from therapy until relapse, progression, or death from any cause.
- Overall Survival (OS) [2 years]
Estimated 2-year Overall Survival (OS), as well as plots of OS, will be produced using the method of Kaplan-Meier, along with 95% confidence intervals for OS. Overall survival is defined as time from the first chemotherapy administered on trial until death from any cause.
- To Evaluate the Safety and Tolerability of the Regimen by the Percent of Participants With Indicated Adverse Events [22 months]
Adverse events will be summarized using patient level incidence rates so that a patient contributes once to any adverse event. The number and percentage of patients with any adverse event will be summarized for each course. Serious adverse events will be analyzed similarly.
- Percent of Patients Who Proceeded With Transplant [168-252 days (4 courses up to 6 courses of treatment)]
Percentage of patients who received consolidation with high dose therapy and autologous stem cell rescue (HDT/SCR).
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically confirmed new diagnosis of Stage II, III and IV peripheral T-cell NHL not otherwise specified (NOS), anaplastic large cell lymphoma (ALK negative) (ALK positive if international prognostic index [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, immunohistochemistry [IHC] and pathology report from initial diagnosis, if slides are not available, then 8 unstained slides of 4 micron thickness or a representative block should be sent) will be reviewed, and the diagnosis confirmed by University Nebraska Medical Center (UNMC) pathology department (retrospective diagnostic review: treatment may commence prior to the UNMC review)
-
No prior therapy with the exception of prior radiation therapy and 1 cycle of chemotherapy based on current diagnosis and clinical condition
-
Age 19 years or older (the age of consent in Nebraska); age 18 years or older (applicable to states where the age of majority is 18)
-
Expected survival duration of >= six months
-
Karnofsky Performance Status >= 70
-
Absolute neutrophil count (ANC) >= 1000 cells/mm^3, unless due to lymphoma involvement of the bone marrow
-
Platelet Count >= 100 mm^3, unless due to lymphoma involvement of the bone marrow
-
Total bilirubin =< 1.5 x upper normal limit (ULN), or =< 3 x ULN if documented hepatic involvement with lymphoma, or =< 5 x ULN if history of Gilbert's Disease
-
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN (=< 5 x ULN if documented hepatic involvement with lymphoma)
-
Serum potassium within normal range
-
Serum creatinine < 2.0 mg/dL or calculated creatinine clearance (CrCl) > 45 mL/min
-
Prothrombin time (PT) or international normalized ratio (INR), and partial thromboplastin time (PTT) =< 1.5 x ULN unless patient is receiving anticoagulants; if patient is on anticoagulation therapy, levels should be within therapeutic range
-
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) scans will not constitute evaluable disease, unless verified by computed tomography (CT) scan or other appropriate imaging
-
Patients with measurable disease must have at least one objective measurable disease parameter; a clearly defined, bidimensionally measurable defect or mass measuring at least 2 cm in diameter on a CT scan will constitute measurable disease; proof of lymphoma in the liver is required by a confirmation biopsy
-
Women must not be pregnant or breast-feeding due to teratogenic effects of chemotherapy
-
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; 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 positive for human immunodeficiency virus (HIV), human T-lymphotropic virus type 1 (HTLV-1), or infectious hepatitis, type A, B or C or active hepatitis
-
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, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment
-
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
-
Concomitant administration of nonsteroidal anti-inflammatory drugs (NSAIDs) and trimethoprim/sulfamethoxazole will not be allowed, since these may result in delayed clearance of pralatrexate
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic in Arizona | Scottsdale | Arizona | United States | 85259 |
| 2 | Stanford University | Stanford | California | United States | 94305 |
| 3 | Emory University School Of Medicine | Atlanta | Georgia | United States | 30308 |
| 4 | University of Chicago | Chicago | Illinois | United States | 60637 |
| 5 | University of Massachusetts Medical School | Worcester | Massachusetts | United States | 01655 |
| 6 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
| 7 | Siteman Cancer Center at Washington University | Saint Louis | Missouri | United States | 63110 |
| 8 | UNMC Eppley Cancer Center at the University of Nebraska Medical Center | Omaha | Nebraska | United States | 68198-6805 |
| 9 | Duke University Medical Center | Durham | North Carolina | United States | 27710 |
Sponsors and Collaborators
- University of Nebraska
- National Cancer Institute (NCI)
- Spectrum Pharmaceuticals, Inc
Investigators
- Principal Investigator: Julie Vose, University of Nebraska
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- 569-10
- NCI-2011-00254
- P30CA036727
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Chemotherapy and Enzyme Inhibitor Therapy |
|---|---|
| Arm/Group Description | "A" Treatment: Cyclophosphamide,Etoposide, Vincristine and Prednisone (CEOP) "B" Treatment: Pralatrexate (P) "A" cycles (CEOP) of the treatment regimen are 14 days, followed by " B" cycles (P) which are 21 days, followed by 7 days of rest for a total of 42 days per course, unless criteria are met for stopping or holding treatment or to a maximum of 6 courses. Patients with Complete Response (CR) or Partial Response (PR), per investigators discretion, may then undergo hematopoietic stem cell collection and administration of standard preparative regimen followed by hematopoietic stem cell transplantation. |
| Period Title: Overall Study | |
| STARTED | 34 |
| COMPLETED | 33 |
| NOT COMPLETED | 1 |
Baseline Characteristics
| Arm/Group Title | Treatment (Chemotherapy and Enzyme Inhibitor Therapy) |
|---|---|
| Arm/Group Description | Cyclophosphamide and vincristine sulfate by IV on day 1, etoposide IV on days 1-3 or by mouth (PO), once a day (QD) on days 2-3, and prednisone PO QD on days 1-5 (CEOP administration). Patients also receive pralatrexate IV over 3-5 minutes on days 15, 22, and 29 (P administration). Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with CR or PR, per investigators discretion, may then undergo hematopoietic stem cell collection and administration of standard preparative regimen followed by hematopoietic stem cell transplantation. prednisone: Given PO cyclophosphamide: Given IV etoposide: Given PO or IV vincristine sulfate: Given IV pralatrexate: Given IV laboratory biomarker analysis: Correlative studies comparative genomic hybridization: Correlative studies gene expression analysis: Correlative studies nucleic acid sequencing: Correlative studies mutation analysis |
| Overall Participants | 33 |
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
62
|
| Sex: Female, Male (Count of Participants) | |
| Female |
9
27.3%
|
| Male |
24
72.7%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
0
0%
|
| Not Hispanic or Latino |
30
90.9%
|
| Unknown or Not Reported |
3
9.1%
|
| Region of Enrollment (Count of Participants) | |
| United States |
33
100%
|
Outcome Measures
| Title | Complete Response Rate of Cyclophosphamide, Etoposide, Vincristine and Prednisone (CEOP) and Pralatrexate (P) Treatment |
|---|---|
| Description | Complete Response Rate (CR) was reported at the end of the CEOP-P (6 courses for patients not receiving transplant and 4-6 courses for patients receiving transplant). Response assessment was performed by computerized tomography (CT) or positron emission tomography (PET)/CT based on the investigator's preference after cycles 2, 4 and 6. Response was assessed by the treating physician according to the Cheson Revised response criteria (Cheson et al,, 2007) or International Harmonization Project criteria (Cheson, 2007), based on imaging modality used. Complete Response Definition: Disappearance of all evidence of disease Nodal Masses: (a) [18F]fluorodeoxyglucose(FDG)-avid or PET positive prior to therapy; mass of any size permitted if PETnegative (b) Variably FDG-avid or PET negative; regression to normal size on CT Spleen, Liver: Not palpable, nodules disappeared Bone Marrow: Infiltrate cleared on repeat biopsy; if indeterminate by morphology, immunohistochemistry should be negative |
| Time Frame | 168 days - 252 days (4-6 courses; 42 days per course) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Treatment (Chemotherapy and Enzyme Inhibitor Therapy) |
|---|---|
| Arm/Group Description | Patients receive cyclophosphamide IV and vincristine sulfate IV on day 1, etoposide IV on days 1-3 or PO QD on days 2-3, and prednisone PO QD on days 1-5 (CEOP administration). Patients also receive pralatrexate IV over 3-5 minutes on days 15, 22, and 29 (P administration). Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with CR or PR, per investigators discretion, may then undergo hematopoietic stem cell collection and administration of standard preparative regimen followed by hematopoietic stem cell transplantation. prednisone: Given PO cyclophosphamide: Given IV etoposide: Given PO or IV vincristine sulfate: Given IV pralatrexate: Given IV laboratory biomarker analysis: Correlative studies comparative genomic hybridization: Correlative studies gene expression analysis: Correlative studies nucleic acid sequencing: Correlative studies mutation analysis: Correlative studies |
| Measure Participants | 33 |
| Number [percentage of participants analyzed] |
52
157.6%
|
| Title | Overall Response Rates (ORR)= (Complete Response Rates (CR) + Partial Response Rates (PR)) |
|---|---|
| Description | Every patient who fulfills all aspects of patient eligibility who receives at least 2 complete courses of chemotherapy will be evaluable for the response endpoint. Response rates will be descriptively summarized using percentages and 95% confidence intervals. Complete Response Definition: Defined in Primary Objective Partial Response Definition: Regression of measurable disease and no new sites, Nodal Masses: > 50% decrease in sum of the product of the diameters (SPD) of up to 6 largest dominant masses; no increase in size of other nodes FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site Variably FDG-avid or PET negative; regression on CT Spleen, Liver:> 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen Bone Marrow: Irrelevant if positive prior to therapy; cell type should be specified |
| Time Frame | 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Treatment (Chemotherapy and Enzyme Inhibitor Therapy) |
|---|---|
| Arm/Group Description | Patients receive cyclophosphamide IV and vincristine sulfate IV on day 1, etoposide IV on days 1-3 or PO QD on days 2-3, and prednisone PO QD on days 1-5 (CEOP administration). Patients also receive pralatrexate IV over 3-5 minutes on days 15, 22, and 29 (P administration). Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with CR or PR, per investigators discretion, may then undergo hematopoietic stem cell collection and administration of standard preparative regimen followed by hematopoietic stem cell transplantation. prednisone: Given PO cyclophosphamide: Given IV etoposide: Given PO or IV vincristine sulfate: Given IV pralatrexate: Given IV laboratory biomarker analysis: Correlative studies comparative genomic hybridization: Correlative studies gene expression analysis: Correlative studies nucleic acid sequencing: Correlative studies mutation analysis: Correlative studies |
| Measure Participants | 33 |
| Number [percentage of participants analyzed] |
70
212.1%
|
| Title | Event Free Survival (EFS) |
|---|---|
| Description | Estimated 2-year Event Free Survival (EFS), as well as plots of EFS, will be produced using the method of Kaplan-Meier, along with 95% confidence intervals for EFS. Event-free survival is defined as time from therapy until relapse, progression, or death from any cause. |
| Time Frame | 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All evaluable patients irrespective of the total number of cycles of therapy received were included in the EFS and OS analyses. |
| Arm/Group Title | Treatment (Chemotherapy and Enzyme Inhibitor Therapy) |
|---|---|
| Arm/Group Description | Patients receive cyclophosphamide IV and vincristine sulfate IV on day 1, etoposide IV on days 1-3 or PO QD on days 2-3, and prednisone PO QD on days 1-5 (CEOP administration). Patients also receive pralatrexate IV over 3-5 minutes on days 15, 22, and 29 (P administration). Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with CR or PR, per investigators discretion, may then undergo hematopoietic stem cell collection and administration of standard preparative regimen followed by hematopoietic stem cell transplantation. prednisone: Given PO cyclophosphamide: Given IV etoposide: Given PO or IV vincristine sulfate: Given IV pralatrexate: Given IV laboratory biomarker analysis: Correlative studies comparative genomic hybridization: Correlative studies gene expression analysis: Correlative studies nucleic acid sequencing: Correlative studies mutation analysis: Correlative studies |
| Measure Participants | 33 |
| Number (95% Confidence Interval) [percentage of participants analyzed] |
39
118.2%
|
| Title | Overall Survival (OS) |
|---|---|
| Description | Estimated 2-year Overall Survival (OS), as well as plots of OS, will be produced using the method of Kaplan-Meier, along with 95% confidence intervals for OS. Overall survival is defined as time from the first chemotherapy administered on trial until death from any cause. |
| Time Frame | 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All evaluable patients irrespective of the total number of cycles of therapy received were included in EFS and OS analyses. |
| Arm/Group Title | Treatment (Chemotherapy and Enzyme Inhibitor Therapy) |
|---|---|
| Arm/Group Description | Patients receive cyclophosphamide IV and vincristine sulfate IV on day 1, etoposide IV on days 1-3 or PO QD on days 2-3, and prednisone PO QD on days 1-5 (CEOP administration). Patients also receive pralatrexate IV over 3-5 minutes on days 15, 22, and 29 (P administration). Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with CR or PR, per investigators discretion, may then undergo hematopoietic stem cell collection and administration of standard preparative regimen followed by hematopoietic stem cell transplantation. prednisone: Given PO cyclophosphamide: Given IV etoposide: Given PO or IV vincristine sulfate: Given IV pralatrexate: Given IV laboratory biomarker analysis: Correlative studies comparative genomic hybridization: Correlative studies gene expression analysis: Correlative studies nucleic acid sequencing: Correlative studies mutation analysis: Correlative studies |
| Measure Participants | 33 |
| Number (95% Confidence Interval) [percentage of participants analyzed] |
60
181.8%
|
| Title | To Evaluate the Safety and Tolerability of the Regimen by the Percent of Participants With Indicated Adverse Events |
|---|---|
| Description | Adverse events will be summarized using patient level incidence rates so that a patient contributes once to any adverse event. The number and percentage of patients with any adverse event will be summarized for each course. Serious adverse events will be analyzed similarly. |
| Time Frame | 22 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All eligible patients who received at least one cycle of chemotherapy were evaluable for toxicity. |
| Arm/Group Title | Treatment (Chemotherapy and Enzyme Inhibitor Therapy) |
|---|---|
| Arm/Group Description | Patients receive cyclophosphamide IV and vincristine sulfate IV on day 1, etoposide IV on days 1-3 or PO QD on days 2-3, and prednisone PO QD on days 1-5 (CEOP administration). Patients also receive pralatrexate IV over 3-5 minutes on days 15, 22, and 29 (P administration). Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with CR or PR, per investigators discretion, may then undergo hematopoietic stem cell collection and administration of standard preparative regimen followed by hematopoietic stem cell transplantation. prednisone: Given PO cyclophosphamide: Given IV etoposide: Given PO or IV vincristine sulfate: Given IV pralatrexate: Given IV laboratory biomarker analysis: Correlative studies comparative genomic hybridization: Correlative studies gene expression analysis: Correlative studies nucleic acid sequencing: Correlative studies mutation analysis: Correlative studies |
| Measure Participants | 33 |
| Grade 3-4 anaemia |
27
81.8%
|
| Grade 3-4 thrombocoytopenia |
12
36.4%
|
| Grade 3-4 febrile neutropenia |
18
54.5%
|
| Grade 3-4 mucositis |
18
54.5%
|
| Grade 3-4 sepsis |
15
45.5%
|
| Grade 3-4 increased creatinine |
12
36.4%
|
| Grade 3-4 liver transaminases |
12
36.4%
|
| Title | Percent of Patients Who Proceeded With Transplant |
|---|---|
| Description | Percentage of patients who received consolidation with high dose therapy and autologous stem cell rescue (HDT/SCR). |
| Time Frame | 168-252 days (4 courses up to 6 courses of treatment) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Thirty-three patients were analyzed. One patient withdrew consent before starting therapy. |
| Arm/Group Title | Treatment |
|---|---|
| Arm/Group Description | "A" Treatment: Cyclophosphamide,Etoposide, Vincristine and Prednisone (CEOP) "B" Treatment: Pralatrexate (P) "A" cycles (CEOP) of the treatment regimen are 14 days, followed by " B" cycles (P) which are 21 days, followed by 7 days of rest for a total of 42 days per course, unless criteria are met for stopping or holding treatment or to a maximum of 6 courses. Patients with Complete Response (CR) or Partial Response (PR), per investigators discretion, may then undergo hematopoietic stem cell collection and administration of standard preparative regimen followed by hematopoietic stem cell transplantation. |
| Measure Participants | 33 |
| Count of Participants [Participants] |
15
45.5%
|
Adverse Events
| Time Frame | 20 months | |
|---|---|---|
| Adverse Event Reporting Description | Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0) | |
| Arm/Group Title | Treatment (Chemotherapy and Enzyme Inhibitor Therapy) | |
| Arm/Group Description | Patients receive cyclophosphamide IV and vincristine sulfate IV on day 1, etoposide IV on days 1-3 or PO QD on days 2-3, and prednisone PO QD on days 1-5 (CEOP administration). Patients also receive pralatrexate IV over 3-5 minutes on days 15, 22, and 29 (P administration). Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with CR or PR, per investigators discretion, may then undergo hematopoietic stem cell collection and administration of standard preparative regimen followed by hematopoietic stem cell transplantation. prednisone: Given PO cyclophosphamide: Given IV etoposide: Given PO or IV vincristine sulfate: Given IV pralatrexate: Given IV laboratory biomarker analysis: Correlative studies comparative genomic hybridization: Correlative studies gene expression analysis: Correlative studies nucleic acid sequencing: Correlative studies mutation analysis: Correlative studies | |
All Cause Mortality |
||
| Treatment (Chemotherapy and Enzyme Inhibitor Therapy) | ||
| Affected / at Risk (%) | # Events | |
| Total | 12/33 (36.4%) | |
Serious Adverse Events |
||
| Treatment (Chemotherapy and Enzyme Inhibitor Therapy) | ||
| Affected / at Risk (%) | # Events | |
| Total | 13/33 (39.4%) | |
| Blood and lymphatic system disorders | ||
| Febrile neutropenia | 5/33 (15.2%) | 5 |
| Cardiac disorders | ||
| Sinus tachycardia | 1/33 (3%) | 1 |
| Thrombotic thrombocytopenic purpura | 1/33 (3%) | 1 |
| Gastrointestinal disorders | ||
| Mucositis oral | 1/33 (3%) | 1 |
| General disorders | ||
| Fever | 4/33 (12.1%) | 6 |
| Hepatobiliary disorders | ||
| Hepatic failure | 1/33 (3%) | 1 |
| Infections and infestations | ||
| Lung Infection | 3/33 (9.1%) | 4 |
| Sepsis | 5/33 (15.2%) | 5 |
| Infections and infestations - Other, specify | 1/33 (3%) | 1 |
| Injury, poisoning and procedural complications | ||
| Kidney anastomotic leak | 1/33 (3%) | 1 |
| Investigations | ||
| Blood bilirubin increased | 1/33 (3%) | 1 |
| Neutrophil count decreased | 3/33 (9.1%) | 3 |
| White blood cell decreased | 1/33 (3%) | 1 |
| Platelet count decreased | 1/33 (3%) | 1 |
| Aspartate aminotransferase increased | 1/33 (3%) | 1 |
| Alanine aminotransferase increased | 1/33 (3%) | 1 |
| Metabolism and nutrition disorders | ||
| Hyponatremia | 1/33 (3%) | 1 |
| Hyperkalemia | 1/33 (3%) | 1 |
| Anorexia | 1/33 (3%) | 1 |
| Hypermagnesemia | 1/33 (3%) | 1 |
| Nervous system disorders | ||
| Headache | 1/33 (3%) | 1 |
| Encephalopathy | 1/33 (3%) | 1 |
| Psychiatric disorders | ||
| Agitation | 1/33 (3%) | 1 |
| Renal and urinary disorders | ||
| Renal and urinary disorders - Other, specify | 1/33 (3%) | 1 |
| Reproductive system and breast disorders | ||
| Hypoxia | 2/33 (6.1%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 1/33 (3%) | 1 |
| Bronchospasm | 1/33 (3%) | 1 |
| Pleural effusion | 1/33 (3%) | 1 |
| Atelectasis | 1/33 (3%) | 1 |
| Pulmonary Edema | 1/33 (3%) | 1 |
| Respiratory, thoracic and mediastinal disorders - Other, specify | 1/33 (3%) | 1 |
| Respiratory Failure | 2/33 (6.1%) | 3 |
| Dyspnea | 1/33 (3%) | 1 |
| Stridor | 1/33 (3%) | 1 |
| Vascular disorders | ||
| Vascular disorders - Other, specify | 1/33 (3%) | 1 |
| Hypotension | 1/33 (3%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Treatment (Chemotherapy and Enzyme Inhibitor Therapy) | ||
| Affected / at Risk (%) | # Events | |
| Total | 19/33 (57.6%) | |
| Blood and lymphatic system disorders | ||
| Blood and lymphatic system disorders - Other, specify | 2/33 (6.1%) | 5 |
| Anemia | 7/33 (21.2%) | 14 |
| Gastrointestinal disorders | ||
| Mucositis oral | 3/33 (9.1%) | 4 |
| General disorders | ||
| Fever | 3/33 (9.1%) | 3 |
| Investigations | ||
| Neutrophil count decreased | 7/33 (21.2%) | 9 |
| Creatinine increased | 3/33 (9.1%) | 4 |
| White blood cell decreased | 3/33 (9.1%) | 3 |
| Metabolism and nutrition disorders | ||
| hypocalcemia | 3/33 (9.1%) | 7 |
| Hyponatremia | 3/33 (9.1%) | 3 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT 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 | Julie M. Vose, M.D. |
|---|---|
| Organization | University of Nebraska Medical Center |
| Phone | 402-559-3848 |
| jmvose@unmc.edu |
- 569-10
- NCI-2011-00254
- P30CA036727