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

NCT ID: NCT01336933

Last Updated: 2023-09-22

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

34 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-07-06

Study Completion Date

2016-12-28

Brief Summary

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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

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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.

Conditions

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Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Hepatosplenic T-cell Lymphoma Peripheral T-cell Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

prednisone

Intervention Type DRUG

Given PO

cyclophosphamide

Intervention Type DRUG

Given IV

etoposide

Intervention Type DRUG

Given PO or IV

Vincristine

Intervention Type DRUG

Given IV

pralatrexate

Intervention Type DRUG

Given IV

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

comparative genomic hybridization

Intervention Type GENETIC

Correlative studies

gene expression analysis

Intervention Type GENETIC

Correlative studies

nucleic acid sequencing

Intervention Type GENETIC

Correlative studies

mutation analysis

Intervention Type GENETIC

Correlative studies

immunohistochemistry staining method

Intervention Type OTHER

Correlative studies

microarray analysis

Intervention Type GENETIC

Correlative studies

RNA analysis

Intervention Type GENETIC

Correlative studies

Interventions

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prednisone

Given PO

Intervention Type DRUG

cyclophosphamide

Given IV

Intervention Type DRUG

etoposide

Given PO or IV

Intervention Type DRUG

Vincristine

Given IV

Intervention Type DRUG

pralatrexate

Given IV

Intervention Type DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type OTHER

comparative genomic hybridization

Correlative studies

Intervention Type GENETIC

gene expression analysis

Correlative studies

Intervention Type GENETIC

nucleic acid sequencing

Correlative studies

Intervention Type GENETIC

mutation analysis

Correlative studies

Intervention Type GENETIC

immunohistochemistry staining method

Correlative studies

Intervention Type OTHER

microarray analysis

Correlative studies

Intervention Type GENETIC

RNA analysis

Correlative studies

Intervention Type GENETIC

Other Intervention Names

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DeCortin Deltra CPM CTX Cytoxan Endoxan Endoxana EPEG VP-16 VP-16-213 leurocristine sulfate VCR Vincasar PFS FOLOTYN PDX comparative genomic analysis Gene Sequencing Molecular Biology, Nucleic Acid Sequencing immunohistochemistry gene expression profiling

Eligibility Criteria

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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

* 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

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Spectrum Pharmaceuticals, Inc

INDUSTRY

Sponsor Role collaborator

University of Nebraska

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Julie M Vose

Role: PRINCIPAL_INVESTIGATOR

University of Nebraska

Locations

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Mayo Clinic, Arizona

Scottsdale, Arizona, United States

Site Status

Stanford University

Stanford, California, United States

Site Status

Emory University School Of Medicine

Atlanta, Georgia, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

University of Massachusetts Medical School

Worcester, Massachusetts, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Siteman Cancer Center, Washington University

St Louis, Missouri, United States

Site Status

Eppley Cancer Center, University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 26627450 (View on PubMed)

Other Identifiers

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NCI-2011-00254

Identifier Type: REGISTRY

Identifier Source: secondary_id

P30CA036727

Identifier Type: NIH

Identifier Source: secondary_id

View Link

0569-10-FB

Identifier Type: -

Identifier Source: org_study_id

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