Study of Pralatrexate to Treat Participants With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma

October 7, 2021 updated by: Spectrum Pharmaceuticals, Inc

A Phase 2, Single-arm, Open-label, Multi-center Study of Pralatrexate in Patients With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma

The purpose of this study is to determine whether pralatrexate, given with vitamin B12 and folic acid, is effective in the treatment of relapsed or refractory B-cell Non-Hodgkin's lymphoma (NHL). The study will also investigate the safety of pralatrexate with vitamin B12 and folic acid in this participant population. Additionally, this study includes the collection of blood samples to investigate the pharmacokinetics (PK) of pralatrexate in this participant population (PK is the activity of a drug in the body over a period of time, including how the drug is absorbed, distributed in the body, localized in the tissues, and excreted from the body).

Study Overview

Study Type

Interventional

Enrollment (Actual)

29

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • California
      • Beverly Hills, California, United States, 90211
        • Tower Cancer Research Foundation
    • Idaho
      • Post Falls, Idaho, United States, 83854
        • Kootenai Cancer Center
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
    • Kentucky
      • Louisville, Kentucky, United States, 40245
        • Owsley Brown Frazier Cancer Center
    • Louisiana
      • Shreveport, Louisiana, United States, 71101
        • Overton Brooks VA Medical Center
    • Montana
      • Billings, Montana, United States, 59102
        • Frontier Cancer Center and Blood Institute
    • New York
      • New York, New York, United States, 10016
        • New York University Hospital
    • Oregon
      • Portland, Oregon, United States, 97225
        • Providence Cancer Center
    • Tennessee
      • Memphis, Tennessee, United States, 38120
        • The West Clinic (ACORN)
    • Wisconsin
      • La Crosse, Wisconsin, United States, 54601
        • Gundersen Lutheran
      • Madison, Wisconsin, United States, 53705-2275
        • University of Wisconsin, Paul P. Carbone Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically/cytologically confirmed, measurable (lesion or node =2 cm by CT [at least 1 cm if by spiral CT]) B-cell Non-Hodgkin's Lymphoma, using the Revised European American Lymphoma (REAL) World Health Organization (WHO) disease classification
  • Progressive or persistent disease after ≥ 1 prior treatment(s)
  • Recovered from toxic effects of prior treatment
  • At least 4 weeks since most recent cytotoxic therapy
  • Easter Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Adequate blood, liver, and kidney functions as defined by laboratory levels
  • 1.0 mg/day orally of folic acid for at least 7 days prior & 1 mg intramuscular of vitamin B12 within 10 weeks of the planned start of pralatrexate
  • Females of childbearing potential must agree to use medically acceptable birth control from start of pralatrexate until at least 30 days after the last administration of pralatrexate and must have a negative serum pregnancy test within 14 days prior to the first day of study treatment
  • Males who are not surgically sterile must agree to use medically acceptable birth control from start of pralatrexate until at least 90 days after the last administration of pralatrexate
  • Available for repeat dosing and follow-up
  • Able to give written informed consent

Exclusion Criteria:

  • Relapsed participants with diffuse large B-cell lymphoma (DLBCL) who are candidates for high-dose therapy and autologous stem cell transplantation (SCT) and for whom high-dose therapy and autologous SCT is a standard curative option
  • Active concurrent malignancy (except non-melanoma skin cancer or carcinoma in situ of the cervix). If there is a history of prior malignancies other than those exceptions listed above, the participant must be disease-free for ≥ 5 years. Participants with other prior malignancies < 5 years before study entry may still be enrolled if they have received treatment resulting in complete resolution of the cancer and currently have no clinical, radiologic, or laboratory evidence of active or recurrent disease
  • Congestive heart failure Class III/IV according to the New York Heart Association Functional Classification
  • Uncontrolled hypertension
  • Known human immunodeficiency virus (HIV)-positive diagnosis
  • Symptomatic central nervous system (CNS) metastases or lesions for which treatment is required. Participants who received prophylactic CNS treatment are eligible.
  • Participants who have undergone an allogeneic SCT
  • Participants who have relapsed < 100 days from the time of an autologous SCT
  • Participants with disease refractory to peripheral blood SCT or who have relapsed < 100 days from the time of transplant
  • Active uncontrolled infection, underlying medical condition, or other serious illness that would impair the ability of the participant to receive protocol treatment.
  • Major surgery within 14 days of enrollment
  • Receipt of any conventional chemotherapy or radiation therapy (encompassing a substantial [> 10%] amount of bone marrow) within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to study treatment or planned use during the course of the study
  • Receipt of systemic corticosteroids within 1 week of study treatment, unless participant has been taking a continuous dose of no more than 10 mg/day of prednisone or its equivalent for at least 1 month
  • Use of any investigational drugs, biologics, or devices within 4 weeks prior to study treatment or planned use during the course of the study
  • Previous exposure to pralatrexate
  • Females who are pregnant or breastfeeding

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pralatrexate

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.

Pralatrexate injection administered as intravenous (IV) push
Other Names:
  • FOLOTYN
  • PDX
  • (RS)-10-propargyl-10-deazaaminopterin
1 mg intramuscular (IM) injection
Other Names:
  • Cyanocobalamin
Oral 1 mg tablet
Other Names:
  • Vitamin B9
  • Folate
  • Folacin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: Up to 24 months
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.
Up to 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Response (DOR)
Time Frame: Up to 24 months
The Duration of Response was defined as the time (in months) from the date the measurement criteria were first met for CR or PR (whichever status was recorded first) until the first subsequent date that relapse or progression was documented. It was assessed according to IWC with or without PET, subject to its availability. Per IWC, progression was defined as a ≥50% increase from the nadir in the individual sum of the products of the diameters of any index lesion; the reappearance of pathology, enlargement of liver/spleen, or unequivocal progression of non-measurable disease or appearance of any new lesions.
Up to 24 months
Progression Free Survival (PFS)
Time Frame: Up to 24 months
Progression-free survival (PFS) was the duration of time (in months) from first administration of study treatment to date of first documented progression or death from any cause. It was based on tumor assessments made according to the IWC with or without PET scans, subject to their availability. Per IWC, progression was defined as a ≥50% increase from the nadir in the individual sum of the products of the diameters of any index lesion; the reappearance of pathology, enlargement of liver/spleen, or unequivocal progression of non-measurable disease or appearance of any new lesions.
Up to 24 months
Overall Survival (OS)
Time Frame: Up to 24 months
Overall Survival was the time (in months) from first administration of study treatment until the date of death.
Up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2009

Primary Completion (Actual)

August 1, 2012

Study Completion (Actual)

August 1, 2012

Study Registration Dates

First Submitted

October 19, 2009

First Submitted That Met QC Criteria

October 19, 2009

First Posted (Estimate)

October 21, 2009

Study Record Updates

Last Update Posted (Actual)

November 5, 2021

Last Update Submitted That Met QC Criteria

October 7, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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