Know Cancer

forgot password

A Phase 1 Dose Escalation Safety/Tolerance Study of PPI-2458 in Subjects With Non-Hodgkin’s Lymphoma and Solid Tumors

Phase 1
18 Years
Not Enrolling
Non-Hodgkin's Lymphoma,, Solid Tumors

Thank you

Trial Information

A Phase 1 Dose Escalation Safety/Tolerance Study of PPI-2458 in Subjects With Non-Hodgkin’s Lymphoma and Solid Tumors

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.

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

- 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

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Principal Investigator

Paul Eder, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Dana-Farber Cancer Institute


United States: Food and Drug Administration

Study ID:




Start Date:

December 2004

Completion Date:

July 2007

Related Keywords:

  • Non-Hodgkin's Lymphoma,
  • Solid Tumors
  • non-Hodgkin lymphoma
  • non-Hodgkin’s lymphoma
  • NHL
  • MetAP2
  • Solid Tumors
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Neoplasms



Beth Israel Deaconess Medical Center Boston, Massachusetts  02215
Virginia Oncology Associates Newport News, Virginia  23606
Massachusetts General Hospital Boston, Massachusetts  02114-2617
Dana Farber Cancer Institute Boston, Massachusetts  02115
University of New Mexico Albuquerque, New Mexico  87131
University of Texas, M.D. Anderson Cancer Center Houston, Texas  77030
Columbia University Medical Center New York, New York  10032
Universtiy of Maryland Marlene and Stewart Greenebaum Cancer Center Baltimore, Maryland  21201