Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Closed 18 to 65 NCI NCI-91-C-0156B NCI-MB-273, NCI-T91-0090N, T91-0090

Objectives

I.  Determine, in a Phase I dose-escalating study, the MTD and toxicity of 
interleukin-1-alpha (IL-1A) administered with ICE 
(ifosfamide/carboplatin/etoposide) and autologous bone marrow transplantation 
in patients with metastatic cancer (completed).

II.  Assess bone marrow function following therapy with IL-1A and ICE with and 
without granulocyte colony stimulating factor (G-CSF).

III.  Assess the efficacy of ICE/IL-1 in patients with breast cancer (30 
patients).

Entry Criteria

Disease Characteristics:

Pathologically confirmed (clinical documentation acceptable at relapse)
malignancy in the following tumor categories:
  Breast cancer that is metastatic or locally advanced (Stage III/IV) with
  stable minimal residual disease (no greater than 2 cm) after combination
  chemotherapy

  Non-Hodgkin's lymphoma (FSC, FM, FL, DSC, DL, DM, DIDL, IBL, LBL, SNC) of
  any stage in relapse or having failed appropriate induction chemotherapy

  Hodgkin's lymphoma of any stage that has failed induction chemotherapy:
     In first relapse within 1 year from chemotherapy-induced remission

     In first relapse more than 1 year after chemotherapy-induced remission if
     there is extranodal involvement at relapse

     In second or subsequent relapse (1 may be after radiotherapy) following
     appropriate combination chemotherapy

     Stage IIB/IIIB/IVA and B in relapse following radiotherapy

No evidence of CNS involvement

No evidence of metastatic disease to the pelvis on plain film or bone scan

Negative bilateral bone marrow biopsy required prior to bone marrow harvest
except in patients with follicular center cell (B1- or L25-positive tumors)
with less than 20% bone marrow involvement

Prior/Concurrent Therapy:

Biologic therapy:
  Not specified

Chemotherapy:
  Breast cancer patients:
     Protocol therapy begins after 2 cycles of appropriate combination
     chemotherapy

  All other patients:
     Protocol therapy begins in those achieving CR after 1 cycle of salvage
     chemotherapy and in those with stable minimal residual disease (no more
     than 2 cm) after 2 cycles of salvage chemotherapy

Endocrine therapy:
  Not specified

Radiotherapy:
  Not specified

Surgery:
  Not specified

Patient Characteristics:

Age:
  18 to 65

Performance status:
  Karnofsky 70-100%

Life expectancy:
  At least 60 days

Hematopoietic:
  Not specified

Hepatic:
  Bilirubin no greater than 1.5 mg/dl
  SGOT no greater than 2 x normal
  PT, PTT normal

Renal:
  Creatinine clearance at least 45 ml/min
  Calcium normal

Cardiovascular:
  Ejection fraction at least 40%
  Exercise treadmill test normal
  No history of angina pectoris
  No history of MI
  No history of CHF

Pulmonary:
  DLCO greater than 50% (compensated for Hgb)
  FEV1 greater than 55%
  PO2 greater than 60%

Other:
  Negative serology for HIV and HBsAg
  Good psychiatric and medical risk status
  No pregnant women
  Adequate contraception required of fertile women

Expected Enrollment

It is expected that a total of 85 patients will be entered.

Outline

Growth Factor/Bone Marrow Stem Cell Protection plus 3-Drug Combination 
Chemotherapy with Urothelial Protection followed by Bone Marrow or Peripheral 
Stem Cell Rescue with and without Colony Stimulating Factor Therapy.  
Interleukin-1-alpha (Dainippon), IL-1A; plus ICE:  Ifosfamide, IFF, 
NSC-109724; Carboplatin, CBDCA, NSC-241240; Etoposide, VP-16, NSC-141540; with 
Mesna, NSC-113891; followed by Autologous Bone Marrow Transplant, ABMT, or 
Peripheral Blood Stem Cells, PBSC, with and without Granulocyte Colony 
Stimulating Factor (Amgen), G-CSF, NSC-614629.

Wilson WH, Bryant G, Fox M, et al.: Interleukin-1alpha administered before high-dosed ifosfamide (I), CBDCA (C), and etoposide (E) (ICE) with autologous bone marrow rescue shortens neutrophil recovery: a phase I/II study. [Abstract] Proceedings of the American Society of Clinical Oncology 12: A-937, 289, 1993.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Wyndham Wilson, MD, PhD, Protocol chair		Ph: 301-435-2415 Email: wilsonw@mail.nih.gov