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

NCT01336933 | Completed Phase 2 Results DMC

• 3 other identifiers: 0569-10-FBNCI-2011-00254P30CA036727
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 9

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

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate of Cyclophosphamide, Etoposide, Vincristine and Prednisone (CEOP) and Pralatrexate (P) Treatment

  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

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

Secondary Outcomes (5)

• Overall Response Rates (ORR)= (Complete Response Rates (CR) + Partial Response Rates (PR))

  2 years

• Event Free Survival (EFS)

  2 years

• Overall Survival (OS)

  2 years

• To Evaluate the Safety and Tolerability of the Regimen by the Percent of Participants With Indicated Adverse Events

  22 months

• Percent of Patients Who Proceeded With Transplant

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

Study Arms (1)

Treatment

EXPERIMENTAL

"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; 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

Interventions

prednisone DRUG

Given PO

Also known as: DeCortin, Deltra

Treatment

cyclophosphamide DRUG

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana

Treatment

etoposide DRUG

Given PO or IV

Also known as: EPEG, VP-16, VP-16-213

Treatment

Vincristine DRUG

Given IV

Also known as: leurocristine sulfate, VCR, Vincasar PFS

Treatment

pralatrexate DRUG

Given IV

Also known as: FOLOTYN, PDX

Treatment

laboratory biomarker analysis OTHER

Correlative studies

Treatment

comparative genomic hybridization GENETIC

Correlative studies

Also known as: comparative genomic analysis

Treatment

gene expression analysis GENETIC

Correlative studies

Treatment

nucleic acid sequencing GENETIC

Correlative studies

Also known as: Gene Sequencing, Molecular Biology, Nucleic Acid Sequencing

Treatment

mutation analysis GENETIC

Correlative studies

Treatment

immunohistochemistry staining method OTHER

Correlative studies

Also known as: immunohistochemistry

Treatment

microarray analysis GENETIC

Correlative studies

Also known as: gene expression profiling

Treatment

RNA analysis GENETIC

Correlative studies

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Nebraska: lead
• National Cancer Institute (NCI): collaborator
• Spectrum Pharmaceuticals, Inc: collaborator

Study Sites (9)

Mayo Clinic, Arizona

Scottsdale, Arizona, 85259, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Emory University School Of Medicine

Atlanta, Georgia, 30308, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

University of Massachusetts Medical School

Worcester, Massachusetts, 01655, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Siteman Cancer Center, Washington University

St Louis, Missouri, 63110, United States

Location

Eppley Cancer Center, University of Nebraska Medical Center

Omaha, Nebraska, 68198-6805, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• 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.

  PMID: 26627450 BACKGROUND

MeSH Terms

Conditions

Lymphoma, Large-Cell, Anaplastic; Immunoblastic Lymphadenopathy; Lymphoma, T-Cell, Peripheral

Interventions

Prednisone; Cyclophosphamide; Etoposide; Vincristine; 10-propargyl-10-deazaaminopterin; Comparative Genomic Hybridization; Gene Expression Profiling; Base Sequence; Immunohistochemistry; Microarray Analysis

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphadenopathy

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Glucosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Cytogenetic Analysis; Genetic Techniques; Investigative Techniques; Molecular Diagnostic Techniques; Nucleic Acid Hybridization; Molecular Structure; Biochemical Phenomena; Chemical Phenomena; Genetic Structures; Genetic Phenomena; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Immunologic Techniques; Microchip Analytical Procedures

Results Point of Contact

• Title: Julie M Vose
• Organization: University of Nebraska Medical Center

jmvose@unmc.edu

402-559-3848

Study Officials

• Julie M Vose

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2011
• First Posted: April 18, 2011
• Study Start: July 6, 2011
• Primary Completion: December 28, 2016
• Study Completion: December 28, 2016
• Last Updated: September 22, 2023
• Results First Posted: June 25, 2018

Record last verified: 2023-09

Locations

US (9)