Clinical trial NCT01336933: Combination Chemotherapy and Pralatrexate as First-Line Therapy in Treating Patients With Non-Hodgkin Lymphoma
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Hepatosplenic T-cell Lymphoma
Peripheral T-cell Lymphoma
Lead sponsor: University of Nebraska
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Spectrum Pharmaceuticals, Inc
First posted: 2011-04-18
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Complete Response Rate of Cyclophosphamide, Etoposide, Vincristine and Prednisone (CEOP) and Pralatrexate (P) Treatment
timeFrame: 168 days - 252 days (4-6 courses; 42 days per course)
Secondary outcomes:
measure: Overall Response Rates (ORR)= (Complete Response Rates (CR) + Partial Response Rates (PR))
timeFrame: 2 years
measure: Event Free Survival (EFS)
timeFrame: 2 years
measure: Overall Survival (OS)
timeFrame: 2 years
measure: To Evaluate the Safety and Tolerability of the Regimen by the Percent of Participants With Indicated Adverse Events
timeFrame: 22 months
measure: Percent of Patients Who Proceeded With Transplant
timeFrame: 168-252 days (4 courses up to 6 courses of treatment)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic, Arizona
state: Arizona
city: Stanford
country: United States
facility: Stanford University
state: California
city: Atlanta
country: United States
facility: Emory University School Of Medicine
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Siteman Cancer Center, Washington University
state: Missouri
city: Omaha
country: United States
facility: Eppley Cancer Center, University of Nebraska Medical Center
state: Nebraska
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: University of Nebraska
name: Julie M Vose
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.