Trial record 1 of 1 for:    NCT01336933
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Combination Chemotherapy and Pralatrexate as First-Line Therapy in Treating Patients With Non-Hodgkin Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Spectrum Pharmaceuticals, Inc
Information provided by (Responsible Party):
Julie M Vose, MD, University of Nebraska
ClinicalTrials.gov Identifier:
NCT01336933
First received: March 23, 2011
Last updated: January 20, 2013
Last verified: January 2013
  Purpose

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 Intervention 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 sulfate
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

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Nebraska:

Primary Outcome Measures:
  • CR rate of CEOP and P treatment [ Time Frame: Up to 6 courses ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Overall response rates (complete response rates + partial response rates) [ Time Frame: Up to 6 courses ] [ Designated as safety issue: No ]
    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.

  • EFS [ Time Frame: Time from therapy until relapse, progression, or death from any cause, assessed up to 2 years ] [ Designated as safety issue: No ]
    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.

  • OS [ Time Frame: Time from the first chemotherapy administered on trial until death from any cause, assessed up to 2 years ] [ Designated as safety issue: No ]
    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.

  • Safety and tolerability of the regimen [ Time Frame: Up to 6 courses ] [ Designated as safety issue: Yes ]
    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 intended to receive transplant versus those who actually proceeded with transplant [ Time Frame: After up to 34 subjects receive transplant ] [ Designated as safety issue: No ]
    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.

  • Ability to collect peripheral blood stem cells [ Time Frame: At the end of 4-6 courses for those that go on to transplant ] [ Designated as safety issue: No ]
    The percentage of patients for whom we were able to collect peripheral blood stem cells will be descriptively summarized using percentages and 95% confidence intervals.


Enrollment: 34
Study Start Date: July 2011
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (chemotherapy and enzyme inhibitor therapy)

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.

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 sulfate
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

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 intended to receive transplant versus those who actually 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 sulfate 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 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.

After completion of study treatment, patients are followed up for 2 years (transplant patients) or periodically.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01336933

Locations
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
Spectrum Pharmaceuticals, Inc
Investigators
Principal Investigator: Julie Vose University of Nebraska
  More Information

No publications provided

Responsible Party: Julie M Vose, MD, Principal Investigator, University of Nebraska
ClinicalTrials.gov Identifier: NCT01336933     History of Changes
Other Study ID Numbers: 569-10, NCI-2011-00254, P30CA036727
Study First Received: March 23, 2011
Last Updated: January 20, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Immunoblastic Lymphadenopathy
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Lymphoma, Large-Cell, Anaplastic
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Histologic Type
Neoplasms
Cyclophosphamide
Etoposide phosphate
Etoposide
Prednisone
Vincristine
Aminopterin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on April 16, 2014