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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01336933
Recruitment Status : Completed
First Posted : April 18, 2011
Results First Posted : June 25, 2018
Last Update Posted : June 25, 2018
National Cancer Institute (NCI)
Spectrum Pharmaceuticals, Inc
Information provided by (Responsible Party):
Julie M Vose, MD, University of Nebraska

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
Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Hepatosplenic T-cell Lymphoma Peripheral T-cell Lymphoma Drug: prednisone Drug: cyclophosphamide Drug: etoposide Drug: Vincristine Drug: pralatrexate Other: laboratory biomarker analysis Genetic: comparative genomic hybridization Genetic: gene expression analysis Genetic: nucleic acid sequencing Genetic: mutation analysis Other: immunohistochemistry staining method Genetic: microarray analysis Genetic: RNA analysis Phase 2

Detailed Description:


I. 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.


I. 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.

V. To assess the percentage of patients who proceeded with transplant. VI. To evaluate the ability to collect peripheral blood stem cells after this regimen.


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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 34 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of 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 Non-Hodgkin Lymphoma
Study Start Date : July 2011
Actual Primary Completion Date : December 28, 2016
Actual Study Completion Date : December 28, 2016

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:
  • DeCortin
  • Deltra

Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana

Drug: etoposide
Given PO or IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213

Drug: Vincristine
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS

Drug: pralatrexate
Given IV
Other Names:
  • PDX

Other: laboratory biomarker analysis
Correlative studies

Genetic: comparative genomic hybridization
Correlative studies
Other Name: comparative genomic analysis

Genetic: gene expression analysis
Correlative studies

Genetic: nucleic acid sequencing
Correlative studies
Other Names:
  • Gene Sequencing
  • Molecular Biology, Nucleic Acid Sequencing

Genetic: mutation analysis
Correlative studies

Other: immunohistochemistry staining method
Correlative studies
Other Name: immunohistochemistry

Genetic: microarray analysis
Correlative studies
Other Name: gene expression profiling

Genetic: RNA analysis
Correlative studies

Primary Outcome Measures :
  1. Complete Response Rate of Cyclophosphamide, Etoposide, Vincristine and Prednisone (CEOP) and Pralatrexate (P) Treatment [ Time Frame: 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 :
  1. Overall Response Rates (ORR)= (Complete Response Rates (CR) + Partial Response Rates (PR)) [ Time Frame: 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

  2. Event Free Survival (EFS) [ Time Frame: 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.

  3. Overall Survival (OS) [ Time Frame: 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.

  4. To Evaluate the Safety and Tolerability of the Regimen by the Percent of Participants With Indicated Adverse Events [ Time Frame: 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.

  5. Percent of Patients Who Proceeded With Transplant [ Time Frame: 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).

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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

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

Information from the National Library of Medicine

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

Please refer to this study by its identifier (NCT number): NCT01336933

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United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
United States, California
Stanford University
Stanford, California, United States, 94305
United States, Georgia
Emory University School Of Medicine
Atlanta, Georgia, United States, 30308
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Massachusetts
University of Massachusetts Medical School
Worcester, Massachusetts, United States, 01655
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Siteman Cancer Center at Washington University
Saint Louis, Missouri, United States, 63110
United States, Nebraska
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-6805
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
University of Nebraska
National Cancer Institute (NCI)
Spectrum Pharmaceuticals, Inc
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Principal Investigator: Julie Vose University of Nebraska
Additional Information:
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Responsible Party: Julie M Vose, MD, Principal Investigator, University of Nebraska Identifier: NCT01336933    
Other Study ID Numbers: 569-10
NCI-2011-00254 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
P30CA036727 ( U.S. NIH Grant/Contract )
First Posted: April 18, 2011    Key Record Dates
Results First Posted: June 25, 2018
Last Update Posted: June 25, 2018
Last Verified: May 2018
Additional relevant MeSH terms:
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Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Lymphoma, Large-Cell, Anaplastic
Lymphoma, T-Cell, Peripheral
Immunoblastic Lymphadenopathy
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Etoposide phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Inflammatory Agents