Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as FOLOTYN, PDX, (RS)-10-propargyl-10-deazaaminopterin, 10-Propargyl-10-Deazaaminopterin (PDX)
pralatrexate · 4 trials · 7 indications
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
Objective response rate was defined as the percentage of participants with a complete response (CR) or a partial response (PR). Tumor response was evaluated on the basis of clinical and radiological criteria, assessed according to International Workshop Criteria (IWC) with or without positron emission tomography (PET) scans. Per IWC criteria CR is defined as complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities definitely assignable to non-Hodgkin's lymphoma (NHL) and PR is defined as \>= 50% decrease in sum of the product of the perpendicular diameters (SPD) of the six largest dominant nodes or nodal masses and no increase in size of other nodes, liver or spleen.
OS was defined as the length of time from randomization until death due to any cause. Patients who were alive at the time of the data cut-off date were censored at the last contact date.
Per Response Evaluation Criteria in T-cell and B-cell Lymphoma for target lesions and assessed using computerized tomography (CT) and or Positron emission tomography CT (PET CT) by local investigators: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=50% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
| Arm | Type | Description |
|---|---|---|
| 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. |
| Pralatrexate | EXPERIMENTAL | Participants received pralatrexate at an initial dose of 30 mg/m\^2, as IV push over 30 seconds to 5 minutes via a patent free-flowing IV line containing normal saline on Days 1, 8 and 15 of a 4-week cycle (weekly for 3 weeks with 1 week of rest) until criteria for discontinuation per protocol were met. The initial dose of 30 mg/m\^2 may be reduced to 20 mg/m\^2 weekly, permitted per protocol defined criteria. If pralatrexate 20 mg/m\^2/week was not tolerated, pralatrexate had to be discontinued. Dose re-escalation was not allowed once dose reduction was done. Participants had dietary supplement of vitamin B12 and folic acid along with pralatrexate. Vitamin B12, given as 1mg IM, within 10 weeks of start of pralatrexate dosing, every 8-10 weeks throughout the study and for at least 30 days post last dose of pralatrexate. Folic acid was given 1mg daily, orally, for at least 7 days prior to start of pralatrexate, throughout the study and for at least 30 days post last dose of pralatrexate. |
| Erlotinib | ACTIVE_COMPARATOR | 150 mg orally in tablet form Administered daily 1 hour before or 2 hours after ingestion of food until criteria for discontinuation per the protocol are met. |
| 135 mg/m^2 Pralatrexate 1/2 weeks | EXPERIMENTAL | Pralatrexate (PDX) 135 mg/m\^2 administered as an intravenous (IV) infusion over one hour into a side arm of a running intravenous infusion of normal saline for 1/2 weeks. |
| 30 mg/m^2 Pralatrexate 3/4 weeks | EXPERIMENTAL | PDX 30 mg/m\^2 administered as an IV infusion over 15 minutes into a side arm of a running intravenous infusion of normal saline for 3/4 weeks. |
| 30 mg/m^2 Pralatrexate 6/7 weeks | EXPERIMENTAL | PDX 30 mg/m\^2 administered as an IV infusion over 15 minutes into a side arm of a running intravenous infusion of normal saline for 6/7 weeks. |
| 45 mg/m^2 Pralatrexate 6/7 weeks | EXPERIMENTAL | PDX 45 mg/m\^2 administered as an IV infusion over 15 minutes into a side arm of a running intravenous infusion of normal saline for 6/7 weeks. |
| 270 mg/m^2 Pralatrexate 2/4 weeks | EXPERIMENTAL | PDX (270 mg/m\^2) administered as an IV bolus over 3-5 minutes into a side arm of a running intravenous infusion of normal saline for 2/4 weeks. |
| Name | Type | Description |
|---|---|---|
| prednisone | DRUG | Given PO |
| cyclophosphamide | DRUG | Given IV |
| etoposide | DRUG | Given PO or IV |
| Vincristine | DRUG | Given IV |
| pralatrexate | DRUG | Given IV |
| laboratory biomarker analysis | OTHER | Correlative studies |
| comparative genomic hybridization | GENETIC | Correlative studies |
| gene expression analysis | GENETIC | Correlative studies |
| nucleic acid sequencing | GENETIC | Correlative studies |
| mutation analysis | GENETIC | Correlative studies |
| immunohistochemistry staining method | OTHER | Correlative studies |
| microarray analysis | GENETIC | Correlative studies |
| RNA analysis | GENETIC | Correlative studies |
| Vitamin B12 | DIETARY_SUPPLEMENT | 1 mg intramuscular (IM) injection |
| Folic Acid | DIETARY_SUPPLEMENT | Oral 1 mg tablet |
| Erlotinib | DRUG | 150 mg orally in tablet form Administered daily 1 hour before or 2 hours after ingestion of food until criteria for discontinuation per the protocol are met. |
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, enteropath...
Pralatrexate is an investigational small molecule being studied in oncology for several lymphoma subtypes, including anaplastic large cell lymphoma, B-cell non-Hodgkin lymphoma, and other lymphomas, as well as non-small cell lung cancer. It is in Phase 2 clinical development and is not described as approved.
Pralatrexate targets dihydrofolate reductase (DHFR) and acts as an inhibitor of this enzyme. DHFR is involved in folate metabolism and DNA synthesis, and inhibiting it is the basis for its anticancer activity in the studied lymphoma and lung cancer settings.
Pralatrexate is being developed by Assertio Holdings, Inc., which trades under the ticker ASRT. The company is the sponsor associated with the clinical development program for this agent in lymphoma and non-small cell lung cancer.
Pralatrexate is in Phase 2 clinical development. It is an investigational agent and has not been described as FDA approved. The Phase 2 studies have been completed, and no active trials are currently listed for this drug.
Pralatrexate has been studied in completed trials including NCT01336933, a Phase 2 study in non-Hodgkin lymphoma; NCT00998946, a Phase 2 study in relapsed or refractory B-cell non-Hodgkin lymphoma; NCT00606502, a Phase 2 study in non-small cell lung cancer; and NCT00052442, a Phase 1 study in lymphoma.
Yes, pralatrexate is also known as 10-propargyl-10-deazaaminopterin. This alternative name appears in the title of the Phase 1 trial NCT00052442, which studied the agent in patients with recurrent or refractory non-Hodgkin lymphoma or Hodgkin lymphoma.