Trial Outcomes & Findings for Combination Chemotherapy and Pralatrexate as First-Line Therapy in Treating Patients With Non-Hodgkin Lymphoma (NCT NCT01336933)

Last Updated: 2023-09-22

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

34 participants

Primary outcome timeframe

168 days - 252 days (4-6 courses; 42 days per course)

Results posted on

2023-09-22

Participant Flow

Participant milestones

Participant milestones
Measure	Chemotherapy and Enzyme Inhibitor Therapy "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.
Overall Study STARTED	34
Overall Study COMPLETED	33
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Combination Chemotherapy and Pralatrexate as First-Line Therapy in Treating Patients With Non-Hodgkin Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Chemotherapy and Enzyme Inhibitor Therapy) n=33 Participants 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
Age, Continuous	62 years n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	30 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants
Region of Enrollment United States	33 Participants n=5 Participants

PRIMARY outcome

Timeframe: 168 days - 252 days (4-6 courses; 42 days per course)

Outcome measures

Outcome measures
Measure	Treatment (Chemotherapy and Enzyme Inhibitor Therapy) n=33 Participants 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
Complete Response Rate of Cyclophosphamide, Etoposide, Vincristine and Prednisone (CEOP) and Pralatrexate (P) Treatment	52 percentage of participants analyzed

SECONDARY outcome

Timeframe: 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 1. FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site 2. 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

Outcome measures

Outcome measures
Measure	Treatment (Chemotherapy and Enzyme Inhibitor Therapy) n=33 Participants 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
Overall Response Rates (ORR)= (Complete Response Rates (CR) + Partial Response Rates (PR))	70 percentage of participants analyzed

SECONDARY outcome

Timeframe: 2 years

Population: All evaluable patients irrespective of the total number of cycles of therapy received were included in the EFS and OS analyses.

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.

Outcome measures

Outcome measures
Measure	Treatment (Chemotherapy and Enzyme Inhibitor Therapy) n=33 Participants 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
Event Free Survival (EFS)	39 percentage of participants analyzed Interval 21.0 to 57.0

SECONDARY outcome

Timeframe: 2 years

Population: All evaluable patients irrespective of the total number of cycles of therapy received were included in EFS and OS analyses.

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.

Outcome measures

Outcome measures
Measure	Treatment (Chemotherapy and Enzyme Inhibitor Therapy) n=33 Participants 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
Overall Survival (OS)	60 percentage of participants analyzed Interval 39.0 to 76.0

SECONDARY outcome

Timeframe: 22 months

Population: All eligible patients who received at least one cycle of chemotherapy were evaluable for toxicity.

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.

Outcome measures

Outcome measures
Measure	Treatment (Chemotherapy and Enzyme Inhibitor Therapy) n=33 Participants 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
To Evaluate the Safety and Tolerability of the Regimen by the Percent of Participants With Indicated Adverse Events Grade 3-4 anaemia	27 percentage of participants
To Evaluate the Safety and Tolerability of the Regimen by the Percent of Participants With Indicated Adverse Events Grade 3-4 thrombocoytopenia	12 percentage of participants
To Evaluate the Safety and Tolerability of the Regimen by the Percent of Participants With Indicated Adverse Events Grade 3-4 febrile neutropenia	18 percentage of participants
To Evaluate the Safety and Tolerability of the Regimen by the Percent of Participants With Indicated Adverse Events Grade 3-4 mucositis	18 percentage of participants
To Evaluate the Safety and Tolerability of the Regimen by the Percent of Participants With Indicated Adverse Events Grade 3-4 sepsis	15 percentage of participants
To Evaluate the Safety and Tolerability of the Regimen by the Percent of Participants With Indicated Adverse Events Grade 3-4 increased creatinine	12 percentage of participants
To Evaluate the Safety and Tolerability of the Regimen by the Percent of Participants With Indicated Adverse Events Grade 3-4 liver transaminases	12 percentage of participants

SECONDARY outcome

Timeframe: 168-252 days (4 courses up to 6 courses of treatment)

Population: Thirty-three patients were analyzed. One patient withdrew consent before starting therapy.

Percentage of patients who received consolidation with high dose therapy and autologous stem cell rescue (HDT/SCR).

Outcome measures

Outcome measures
Measure	Treatment (Chemotherapy and Enzyme Inhibitor Therapy) n=33 Participants 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
Percent of Patients Who Proceeded With Transplant	15 Participants

Adverse Events

Treatment (Chemotherapy and Enzyme Inhibitor Therapy)

Serious events: 13 serious events

Other events: 19 other events

Deaths: 12 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Chemotherapy and Enzyme Inhibitor Therapy) n=33 participants at risk 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
General disorders Fever	12.1% 4/33 • Number of events 6 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Infections and infestations Lung Infection	9.1% 3/33 • Number of events 4 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Nervous system disorders Headache	3.0% 1/33 • Number of events 1 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Blood and lymphatic system disorders Febrile neutropenia	15.2% 5/33 • Number of events 5 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Infections and infestations Sepsis	15.2% 5/33 • Number of events 5 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Respiratory, thoracic and mediastinal disorders Cough	3.0% 1/33 • Number of events 1 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Infections and infestations Infections and infestations - Other, specify	3.0% 1/33 • Number of events 1 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Respiratory, thoracic and mediastinal disorders Bronchospasm	3.0% 1/33 • Number of events 1 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Vascular disorders Vascular disorders - Other, specify	3.0% 1/33 • Number of events 1 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Investigations Blood bilirubin increased	3.0% 1/33 • Number of events 1 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Respiratory, thoracic and mediastinal disorders Pleural effusion	3.0% 1/33 • Number of events 1 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Investigations Neutrophil count decreased	9.1% 3/33 • Number of events 3 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Respiratory, thoracic and mediastinal disorders Atelectasis	3.0% 1/33 • Number of events 1 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Respiratory, thoracic and mediastinal disorders Pulmonary Edema	3.0% 1/33 • Number of events 1 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Vascular disorders Hypotension	3.0% 1/33 • Number of events 1 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Nervous system disorders Encephalopathy	3.0% 1/33 • Number of events 1 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Metabolism and nutrition disorders Hyponatremia	3.0% 1/33 • Number of events 1 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify	3.0% 1/33 • Number of events 1 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Metabolism and nutrition disorders Hyperkalemia	3.0% 1/33 • Number of events 1 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Respiratory, thoracic and mediastinal disorders Respiratory Failure	6.1% 2/33 • Number of events 3 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Respiratory, thoracic and mediastinal disorders Dyspnea	3.0% 1/33 • Number of events 1 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Injury, poisoning and procedural complications Kidney anastomotic leak	3.0% 1/33 • Number of events 1 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Reproductive system and breast disorders Hypoxia	6.1% 2/33 • Number of events 2 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Cardiac disorders Sinus tachycardia	3.0% 1/33 • Number of events 1 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Respiratory, thoracic and mediastinal disorders Stridor	3.0% 1/33 • Number of events 1 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Cardiac disorders Thrombotic thrombocytopenic purpura	3.0% 1/33 • Number of events 1 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Gastrointestinal disorders Mucositis oral	3.0% 1/33 • Number of events 1 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Investigations White blood cell decreased	3.0% 1/33 • Number of events 1 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Investigations Platelet count decreased	3.0% 1/33 • Number of events 1 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Metabolism and nutrition disorders Anorexia	3.0% 1/33 • Number of events 1 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Hepatobiliary disorders Hepatic failure	3.0% 1/33 • Number of events 1 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Investigations Aspartate aminotransferase increased	3.0% 1/33 • Number of events 1 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Investigations Alanine aminotransferase increased	3.0% 1/33 • Number of events 1 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Metabolism and nutrition disorders Hypermagnesemia	3.0% 1/33 • Number of events 1 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Renal and urinary disorders Renal and urinary disorders - Other, specify	3.0% 1/33 • Number of events 1 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Psychiatric disorders Agitation	3.0% 1/33 • Number of events 1 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)

Other adverse events

Other adverse events
Measure	Treatment (Chemotherapy and Enzyme Inhibitor Therapy) n=33 participants at risk 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
Investigations Neutrophil count decreased	21.2% 7/33 • Number of events 9 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, specify	6.1% 2/33 • Number of events 5 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Blood and lymphatic system disorders Anemia	21.2% 7/33 • Number of events 14 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Gastrointestinal disorders Mucositis oral	9.1% 3/33 • Number of events 4 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Investigations Creatinine increased	9.1% 3/33 • Number of events 4 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
General disorders Fever	9.1% 3/33 • Number of events 3 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Metabolism and nutrition disorders hypocalcemia	9.1% 3/33 • Number of events 7 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Investigations White blood cell decreased	9.1% 3/33 • Number of events 3 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)
Metabolism and nutrition disorders Hyponatremia	9.1% 3/33 • Number of events 3 • 20 months Adverse Event Reporting: Grade 3 and greater using the CTCAE coding (4.0)

Additional Information

Julie M Vose

University of Nebraska Medical Center

Phone: 402-559-3848

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place