Safety/Tolerance Study of PPI-2458 in Subjects With Non-Hodgkin’s Lymphoma and Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00100347
Recruitment Status : Terminated (terminated due to corporate transaction.)
First Posted : December 30, 2004
Last Update Posted : July 25, 2007
Information provided by:
PRAECIS Pharmaceuticals Inc.

Brief Summary:
The purpose of this multi-center, open-label, escalating dose study is to assess the safety and tolerability of PPI-2458 in subjects with Non-Hodgkin's Lymphoma (NHL)and solid tumors. Subjects will be treated every other day (QOD) with PPI-2458 while being monitored closely for adverse events.

Condition or disease Intervention/treatment Phase
Non-Hodgkin's Lymphoma, Solid Tumors Drug: PPI-2458 Phase 1

Detailed Description:

The study will first determine the dose level that maximally inhibits MetAP2 in white blood cells (WBC). Once this dose level is reached, the study will proceed into the next cohort (dose level) to investigate the dose level that maximally inhibits MetAP2 in tumor tissue biopsies. Free MetAP2 levels (WBC and/or tumor tissue) will be analyzed during the first cycle (28 days) of treatment. Cohorts are expected to enroll every two cycles until the maximum tolerated dose (MTD)is determined.

After the Initial Treatment Phase of two treatment cycles of PPI-2458, subjects may continue into a Continuous Treatment Phase at the discretion of the Investigator. In order to be eligible for the Continuous Treatment Phase of the protocol, subjects must have received some benefit (e.g., stable disease) as assessed by the Investigator within the Initial Treatment Phase and must continue to meet inclusion and exclusion criteria.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 45 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Dose Escalation Safety/Tolerance Study of PPI-2458 in Subjects With Non-Hodgkin’s Lymphoma and Solid Tumors
Study Start Date : December 2004
Actual Study Completion Date : July 2007

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
U.S. FDA Resources

Primary Outcome Measures :
  1. Safety will be determined by clinical adverse events, laboratory abnormalities, withdrawals due to adverse events, and drug-related neurotoxicities.

Secondary Outcome Measures :
  1. Pharmacokinetic assessment of PPI-2458
  2. Pharmacodynamic assessment of PPI-2458

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Subject has the ability to understand the requirements of the study, provide written informed consent, and abide by the requirements of the study
  • Male or female ≥ 18 years of age
  • NHL subjects must have histologically confirmed (by the investigator) diffuse large B cell lymphoma (DLBCL) or follicular lymphoma (FL)- Grade I-III non-Hodgkin’s lymphoma (including transformed subjects) with confirmed failure of prior treatment, defined as: a) Progression following other chemotherapy regimens, radiation therapy, monoclonal antibody therapy, or high dose therapy and autologous stem cell transplantation OR b) Not a candidate for or unwilling to undergo high dose therapy with autologous cell transplantation for DLBCL subjects, OR c) Received at least two previous treatment regimens for FL or relapsed, or progressed, while on or following cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or anthracycline-based regimen for DLBCL subjects Solid tumor subjects must have histologically or cytologically confirmed solid tumor that is either measurable or evaluable and refractory to standard treatment or fow which no curative treatment exists.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 or Karnofsky performance status of 60 - 100%
  • Life expectancy ≥ 2 months
  • Laboratory values: *Absolute neutrophil count (ANC) ≥ 1,500/mm3; *Platelets ≥ 90,000/mm3; *Aspartate aminotransferase (AST) ≤ 2x upper limit of normal (ULN); *Alanine aminotransferase (ALT) ≤ 2x ULN; *Total bilirubin ≤ 1.5x ULN; *Serum creatinine < 1.5x ULN
  • ≥ 3 weeks since chemotherapy, radiation therapy, monoclonal antibody therapy (e.g. rituximab, etc.) or major surgery, and ≥ 12 weeks since radioimmune therapy
  • Results of the two baseline neurodiagnostic nerve conduction velocities (taken at least one week apart) may not vary more than 10%. Response must be well formed and clearl measurable, as judged by the electrophysiology core lab
  • Women of childbearing potential must not be breastfeeding or lactating and must have a negative serum pregnancy test within 72 hours of starting the study
  • Fertile males and females of child-bearing potential must practice medically acceptable contraception
  • Confirmed HIV negative
  • Tumor tissue cohorts only: Subjects must have accessible tumor tissue and be willing to undergo tumor tissue biopsies (2-4 core biopsies)
  • For subjects entering Continuous Treatment Phase: Subjects must have received some benefit from the Initial Treatment Phase of PPI-2458 treatment (e.g., stable disease) as assessed by the Investigator.

Exclusion Criteria:

  • Active central nervous system (CNS) lymphoma or brain metastases as evidenced by clinical symptoms or by computed tomography (CT) scan or magnetic resonance imaging (MRI), or progression from prior imaging
  • A neuropathy ≥ Grade 2
  • Baseline nerve conduction velocities, which vary by more than 10% and are inconsistent and/or poorly formed, as judged by the electrophysiology core lab
  • Requirement for corticosteroids
  • History of allogeneic stem cell transplantation
  • History of seizures
  • Active colitis, peptic ulcers, or Irritable Bowel Disease
  • Any uncontrolled serious medical or psychiatric illness
  • Electrocardiogram (ECG) showing clinically significant atrial or ventricular arrhythmias, 2nd degree or 3rd degree heart block or prolonged QTc interval > 480 msec
  • Subjects taking any drug that is a known clinically relevant inhibitor or inducer of cytochrome P450 3A4.
  • Has received an investigational drug within 21 days of study entry, is currently participating in another study, or is planning to participate in another study during this clinical trial
  • Receiving ongoing pharmacological or radiological treatments for NHL
  • History of mucositis, not related to prior NHL therapy, > Grade 1 within the last year

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00100347

United States, Maryland
Universtiy of Maryland Marlene and Stewart Greenebaum Cancer Center
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, New Mexico
University of New Mexico
Albuquerque, New Mexico, United States, 87131
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
United States, Texas
University of Texas, M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Virginia
Virginia Oncology Associates
Norfolk, Virginia, United States, 23502
Sponsors and Collaborators
PRAECIS Pharmaceuticals Inc.
Principal Investigator: Paul Eder, MD Dana-Farber Cancer Institute Identifier: NCT00100347     History of Changes
Other Study ID Numbers: 2458-04-01
First Posted: December 30, 2004    Key Record Dates
Last Update Posted: July 25, 2007
Last Verified: July 2007

Keywords provided by PRAECIS Pharmaceuticals Inc.:
non-Hodgkin lymphoma
non-Hodgkin’s lymphoma
Solid Tumors

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases