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Trial record 18 of 19 for:    pralatrexate AND PTCL

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.
 
ClinicalTrials.gov Identifier: NCT01336933
Recruitment Status : Completed
First Posted : April 18, 2011
Results First Posted : June 25, 2018
Last Update Posted : June 25, 2018
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Spectrum Pharmaceuticals, Inc
Information provided by (Responsible Party):
Julie M Vose, MD, University of Nebraska

Tracking Information
First Submitted Date  ICMJE March 23, 2011
First Posted Date  ICMJE April 18, 2011
Results First Submitted Date  ICMJE February 4, 2018
Results First Posted Date  ICMJE June 25, 2018
Last Update Posted Date June 25, 2018
Study Start Date  ICMJE July 2011
Actual Primary Completion Date December 28, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 23, 2018)
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
Original Primary Outcome Measures  ICMJE
 (submitted: April 14, 2011)
  • Overall response rate (ORR) [ Time Frame: 24 weeks or up to 36 weeks (4 courses or up to 6 courses) ]
    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 (CR) [ Time Frame: 24 weeks or up to 36 weeks (4 courses or up to 6 courses) ]
    Every patient who fulfills all aspects of patient eligibility who receives at least 2 complete course of chemotherapy will be evaluable for the response endpoint. Response rates will be descriptively summarized using percentages and 95% confidence intervals. A CR rate > 50% would be promising if the toxicity profile is acceptable.
  • Partial response rate (PR) [ Time Frame: 24 weeks or up to 36 weeks (4 courses or up to 6 courses) ]
    Every patient who fulfills all aspects of patient eligibility who receives at least 2 complete course of chemotherapy will be evaluable for the response endpoint. Response rates will be descriptively summarized using percentages and 95% confidence intervals.
Change History Complete list of historical versions of study NCT01336933 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 23, 2018)
  • 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
  • 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.
  • 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.
  • 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.
  • 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).
Original Secondary Outcome Measures  ICMJE
 (submitted: April 14, 2011)
  • Estimated event free survival (EFS) [ Time Frame: 2 years ]
    Event-free survival is defined as time from therapy until relapse, progression, or death from any cause. Estimated 2-year EFS, as well as plots of EFS, will be produced using the method of Kaplan-Meier, along with 95% confidence intervals for EFS.
  • Overall survival (OS) [ Time Frame: 2 years ]
    Overall survival is defined as time from the first chemotherapy administered on trial until death from any cause. Estimated 2-year OS, as well as plots of OS, will be produced using the method of Kaplan-Meier, along with 95% confidence intervals for OS.
  • Percent of patients who intended to receive transplant versus those who actually proceeded with transplant [ Time Frame: (Average) after up to 34 subjects receive transplant ]
    The percentage of patients who intended to receive transplant will be descriptively summarized using percentages at 95% confidence intervals. Among those who intended to receive a transplant, the percentage that proceeded with a transplant will be summarized along with a 95% confidence interval.
  • Incidence of adverse events [ Time Frame: When reported by patients and at days 1&15 physical examinations of each 28 day cycle ]
    Every patient who fulfills all aspects of patient eligibility who receives a partial or complete course of chemotherapy will be 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 cycle. Serious adverse events will be analyzed similarly.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combination Chemotherapy and Pralatrexate as First-Line Therapy in Treating Patients With Non-Hodgkin Lymphoma
Official Title  ICMJE 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
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
Detailed Description

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Anaplastic Large Cell Lymphoma
  • Angioimmunoblastic T-cell Lymphoma
  • Hepatosplenic T-cell Lymphoma
  • Peripheral T-cell Lymphoma
Intervention  ICMJE
  • 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:
    • FOLOTYN
    • 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
Study Arms  ICMJE 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.

Interventions:
  • 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
Publications * Advani RH, Ansell SM, Lechowicz MJ, Beaven AW, Loberiza F, Carson KR, Evens AM, Foss F, Horwitz S, Pro B, Pinter-Brown LC, Smith SM, Shustov AR, Savage KJ, Vose JM. A phase II study of cyclophosphamide, etoposide, vincristine and prednisone (CEOP) Alternating with Pralatrexate (P) as front line therapy for patients with peripheral T-cell lymphoma (PTCL): final results from the T- cell consortium trial. Br J Haematol. 2016 Feb;172(4):535-44. doi: 10.1111/bjh.13855. Epub 2015 Dec 2.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 14, 2011)
34
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 28, 2016
Actual Primary Completion Date December 28, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01336933
Other Study ID Numbers  ICMJE 569-10
NCI-2011-00254 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
P30CA036727 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Julie M Vose, MD, University of Nebraska
Study Sponsor  ICMJE University of Nebraska
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • Spectrum Pharmaceuticals, Inc
Investigators  ICMJE
Principal Investigator: Julie Vose University of Nebraska
PRS Account University of Nebraska
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP