NCT01336933

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

Completed Phase 2 Results posted Last updated 22 September 2023

What this trial tests

Phase 2 trial testing prednisone in Anaplastic Large Cell Lymphoma in 34 participants. Completed in 28 December 2016.

Timeline

6 July 2011

Primary endpoint
28 December 2016

28 December 2016

Quick facts

Lead sponsor	University of Nebraska
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	34
Start date	6 July 2011
Primary completion	28 December 2016
Estimated completion	28 December 2016
Sites	9 locations across United States

Drugs / interventions tested

• prednisone (prednisone) — full drug profile →
• cyclophosphamide (cyclophosphamide) — full drug profile →
• etoposide (etoposide) — full drug profile →
• Vincristine (vincristine) — full drug profile →
• pralatrexate
• laboratory biomarker analysis
• comparative genomic hybridization
• gene expression analysis
• nucleic acid sequencing
• mutation analysis
• immunohistochemistry staining method
• microarray analysis
• RNA analysis

Conditions studied

• Anaplastic Large Cell Lymphoma — all drugs for Anaplastic Large Cell Lymphoma →
• Angioimmunoblastic T-cell Lymphoma — all drugs for Angioimmunoblastic T-cell Lymphoma →
• Hepatosplenic T-cell Lymphoma — all drugs for Hepatosplenic T-cell Lymphoma →
• Peripheral T-cell Lymphoma — all drugs for Peripheral T-cell Lymphoma →

Sponsor

University of Nebraska

Who can join

18 and older, any sex, with Anaplastic Large Cell Lymphoma or Angioimmunoblastic T-cell Lymphoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

Group	Value	95% CI
Treatment (Chemotherapy and Enzyme Inhibitor Therapy)	52

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

Group	Value	95% CI
Treatment (Chemotherapy and Enzyme Inhibitor Therapy)	70

Event Free Survival (EFS) Secondary · 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.

Group	Value	95% CI
Treatment (Chemotherapy and Enzyme Inhibitor Therapy)	39	21 – 57

Overall Survival (OS) Secondary · 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.

Group	Value	95% CI
Treatment (Chemotherapy and Enzyme Inhibitor Therapy)	60	39 – 76

To Evaluate the Safety and Tolerability of the Regimen by the Percent of Participants With Indicated Adverse Events Secondary · 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.

Grade 3-4 anaemia

Group	Value	95% CI
Treatment (Chemotherapy and Enzyme Inhibitor Therapy)	27

Grade 3-4 thrombocoytopenia

Group	Value	95% CI
Treatment (Chemotherapy and Enzyme Inhibitor Therapy)	12

Grade 3-4 febrile neutropenia

Group	Value	95% CI
Treatment (Chemotherapy and Enzyme Inhibitor Therapy)	18

Grade 3-4 mucositis

Group	Value	95% CI
Treatment (Chemotherapy and Enzyme Inhibitor Therapy)	18

Grade 3-4 sepsis

Group	Value	95% CI
Treatment (Chemotherapy and Enzyme Inhibitor Therapy)	15

Grade 3-4 increased creatinine

Group	Value	95% CI
Treatment (Chemotherapy and Enzyme Inhibitor Therapy)	12

Grade 3-4 liver transaminases

Group	Value	95% CI
Treatment (Chemotherapy and Enzyme Inhibitor Therapy)	12

Percent of Patients Who Proceeded With Transplant Secondary · 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).

Group	Value	95% CI
Treatment	15

Adverse events — posted to ClinicalTrials.gov

Time frame: 20 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment (Chemotherapy and Enzyme Inhibitor Therapy)

Serious: 13/33 (39%)

Deaths: 12/33

Serious adverse events (36 terms)

Reaction	System	Treatment (Chemotherapy an…
Febrile neutropenia	Blood and lymphatic system disorders	—
Sepsis	Infections and infestations	—
Fever	General disorders	—
Lung Infection	Infections and infestations	—
Neutrophil count decreased	Investigations	—
Respiratory Failure	Respiratory, thoracic and mediastinal disorders	—
Hypoxia	Reproductive system and breast disorders	—
Headache	Nervous system disorders	—
Cough	Respiratory, thoracic and mediastinal disorders	—
Infections and infestations - Other, specify	Infections and infestations	—
Bronchospasm	Respiratory, thoracic and mediastinal disorders	—
Vascular disorders - Other, specify	Vascular disorders	—
Blood bilirubin increased	Investigations	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—
Atelectasis	Respiratory, thoracic and mediastinal disorders	—
Pulmonary Edema	Respiratory, thoracic and mediastinal disorders	—
Hypotension	Vascular disorders	—
Encephalopathy	Nervous system disorders	—
Hyponatremia	Metabolism and nutrition disorders	—
Respiratory, thoracic and mediastinal disorders - Other, specify	Respiratory, thoracic and mediastinal disorders	—
Hyperkalemia	Metabolism and nutrition disorders	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—
Kidney anastomotic leak	Injury, poisoning and procedural complications	—
Sinus tachycardia	Cardiac disorders	—
Stridor	Respiratory, thoracic and mediastinal disorders	—

Other adverse events (9 terms — click to expand)

Reaction	System	Treatment (Chemotherapy an…
Neutrophil count decreased	Investigations	—
Anemia	Blood and lymphatic system disorders	—
Mucositis oral	Gastrointestinal disorders	—
Creatinine increased	Investigations	—
Fever	General disorders	—
hypocalcemia	Metabolism and nutrition disorders	—
White blood cell decreased	Investigations	—
Hyponatremia	Metabolism and nutrition disorders	—
Blood and lymphatic system disorders - Other, specify	Blood and lymphatic system disorders	—

Most-reported serious reactions: Febrile neutropenia, Sepsis, Fever, Lung Infection, Neutrophil count decreased, Respiratory Failure, Hypoxia, Headache.

Data from ClinicalTrials.gov NCT01336933 adverse events section.

Sponsor's own description

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

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Adult systemic anaplastic large-cell lymphoma: recommendations for diagnosis and management.
   Bennani-Baiti N, Ansell S, Feldman AL. · · 2016 · cited 15× · PMID 26581318 · DOI 10.1586/17474086.2016.1122514