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Phase I Study of MDR Modulation With PSC-833 (NSC# 648265) With a Pilot Study of Cytogenetic Risk-Adapted Consolidation Followed by a Phase II Pilot Study of Immunotherapy With RIL-2 (NSC # 373364) in Previously Untreated Patients With AML< 60 Years


Phase 1/Phase 2
15 Years
59 Years
Not Enrolling
Both
Leukemia

Thank you

Trial Information

Phase I Study of MDR Modulation With PSC-833 (NSC# 648265) With a Pilot Study of Cytogenetic Risk-Adapted Consolidation Followed by a Phase II Pilot Study of Immunotherapy With RIL-2 (NSC # 373364) in Previously Untreated Patients With AML< 60 Years


OBJECTIVES: I. Determine the maximum tolerated dose (MTD) of daunorubicin when used in
combination with etoposide, cytarabine, and PSC 833 (ADEP), and in combination with
etoposide and cytarabine (ADE) in previously untreated patients with acute myelogenous
leukemia who are less than 60 years. II. Determine the MTD of etoposide when used in
combination with a constant dose of daunorubicin and cytarabine (ADE) in these patients.
III. Determine the feasibility and toxic effects of administering postremission therapy in a
risk adapted fashion, such that patients with favorable cytogenetic findings receive three
intensifications with high dose cytarabine (HiDAC), while average to poor risk patients
receive HiDAC/etoposide/filgrastim (G-CSF) for consolidation therapy and stem cell
mobilization followed by peripheral stem cell (PBSC) transplant using busulfan/etoposide as
the preparative regimen. IV. Determine the feasibility and toxic effects of the
consolidation sequence of HiDAC/etoposide/G-CSF followed by 2 courses of HiDAC in patients
who would otherwise receive PBSC transplant, but are unable to do so for logistical or
institutional reasons. V. Determine the feasibility of intermittent administration of high
dose subcutaneous interleukin-2 (IL-2) in combination with continuous low dose subcutaneous
IL-2 in patients recovering from PBSC transplant or intensive consolidation chemotherapy.

OUTLINE: This is a dose escalation study of daunorubicin in the induction therapy portion,
with a separate dose escalation study of etoposide in the same portion. Patients are treated
with three phases of treatment: induction, intensification, and postremission therapy.
Induction therapy: Patients receive cytarabine IV as a continuous infusion on days 1-7 plus
daunorubicin IV over 30 minutes and etoposide IV over 2 hours on days 1-3 (ADE regimen).
Some patients also receive PSC 833 IV as a continuous infusion on days 1-3 (ADEP regimen).
This course may be repeated 14 days later. Cohorts of 9 patients each receive escalating
doses of daunorubicin until the maximum tolerated dose (MTD) is reached. The MTD is defined
as the dose at which 3 of 9 patients experience dose limiting toxicity. Escalations are
conducted separately for the ADE and ADEP regimens. Other cohorts of 9 patients each receive
escalating doses of etoposide with constant doses of daunorubicin in the ADE regimen. The
MTD is described in the same manner. Intensification therapy: Arm I (patients with certain
genetic characteristics in their leukemia cells): Patients receive 3 additional courses of
cytarabine IV over 3 hours, twice a day, for 3 days. Courses are repeated every 28 days. Arm
II (patients who do not have these genetic characteristics): Patients undergo a peripheral
blood stem cell (PBSC) transplant. Patients first receive high dose cytarabine IV over 2
hours on days 1-4, etoposide IV as a continuous infusion on days 1-4, and filgrastim (G-CSF)
subcutaneously beginning on day 5 until blood counts recover. PBSC are then collected.
Approximately 4-6 weeks later, patients receive oral busulfan 4 times a day on days 1-4 and
etoposide IV over 4 hours on day 5. PBSC are reinfused on day 7. G-CSF is administered
subcutaneously beginning on day 7 until blood cell counts recover. Arm III (patients who
cannot undergo a PBSC transplant): Patients receive cytarabine, etoposide, and G-CSF as in
arm II, then high dose cytarabine as in arm I. Postremission therapy (all patients):
Patients receive low dose interleukin-2 (IL-2) by daily injection for 2 weeks. On day 15,
patients begin receiving intermittent high dose IL-2 three days a week. Patients alternate
these courses of IL-2: 14 days of low dose IL-2, 3 days of high dose IL-2, 1 day of rest,
low dose IL-2 for 10 days, then 3 days of high dose IL-2, then 1 day of rest. This course is
repeated 3 times. Patients then receive another 16 day course of low dose IL-2. Patients are
followed at 1 month, then every 3 months for 2 years, then every 6 months for 2 years, then
annually thereafter.

PROJECTED ACCRUAL: Approximately 410 patients will be accrued into this study within 36
months.

Inclusion Criteria


DISEASE CHARACTERISTICS: Histologically proven acute myelogenous leukemia, except M3

PATIENT CHARACTERISTICS: Age: 15 to 59 Performance status: Not specified Life expectancy:
Not specified Hematopoietic: No prior hematologic malignancy, myeloproliferative disorder,
myelodysplastic syndrome, or paroxysmalnocturnal hemoglobinuria No unexplained cytopenias
greater than 3 months in duration Hepatic: Not specified Renal: Not specified

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy No prior treatment
for leukemia except leukapheresis Chemotherapy: No prior chemotherapy except hydroxyurea
which may be used for emergency therapy of hyperleukocytosis Endocrine therapy: Not
specified Radiotherapy: Prior cranial radiation therapy allowed for CNS leukostasis
Surgery: Not specified

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Jonathan E. Kolitz, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Don Monti Comprehensive Cancer Center at North Shore University Hospital

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000065333

NCT ID:

NCT00002925

Start Date:

February 1997

Completion Date:

June 2010

Related Keywords:

  • Leukemia
  • untreated adult acute myeloid leukemia
  • adult acute erythroid leukemia (M6)
  • adult acute myeloblastic leukemia without maturation (M1)
  • adult acute myeloblastic leukemia with maturation (M2)
  • adult acute myelomonocytic leukemia (M4)
  • adult acute monoblastic leukemia (M5a)
  • adult acute megakaryoblastic leukemia (M7)
  • adult acute monocytic leukemia (M5b)
  • adult acute minimally differentiated myeloid leukemia (M0)
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263
Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
Walter Reed Army Medical CenterWashington, District of Columbia  20307-5000
University of Chicago Cancer Research CenterChicago, Illinois  60637
University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
University of Massachusetts Memorial Medical CenterWorcester, Massachusetts  01655
Lineberger Comprehensive Cancer Center, UNCChapel Hill, North Carolina  27599-7295
Duke Comprehensive Cancer CenterDurham, North Carolina  27710
Comprehensive Cancer Center of Wake Forest University Baptist Medical CenterWinston-Salem, North Carolina  27157-1082
Medical University of South CarolinaCharleston, South Carolina  29425-0721
Rhode Island HospitalProvidence, Rhode Island  02903
Vermont Cancer CenterBurlington, Vermont  05401-3498
CCOP - Southern Nevada Cancer Research FoundationLas Vegas, Nevada  89106
University of California San Diego Cancer CenterLa Jolla, California  92093-0658
UCSF Cancer Center and Cancer Research InstituteSan Francisco, California  94115-0128
CCOP - Christiana Care Health ServicesWilmington, Delaware  19899
CCOP - Mount Sinai Medical CenterMiami Beach, Florida  33140
Marlene & Stewart Greenebaum Cancer Center, University of MarylandBaltimore, Maryland  21201
Ellis Fischel Cancer Center - ColumbiaColumbia, Missouri  65203
Barnes-Jewish HospitalSaint Louis, Missouri  63110
Norris Cotton Cancer CenterLebanon, New Hampshire  03756
CCOP - North Shore University HospitalManhasset, New York  11030
State University of New York - Upstate Medical UniversitySyracuse, New York  13210
CCOP - Southeast Cancer Control ConsortiumWinston-Salem, North Carolina  27104-4241
University of Tennessee, Memphis Cancer CenterMemphis, Tennessee  38103
MBCCOP - Massey Cancer CenterRichmond, Virginia  23298-0037
Mount Sinai Medical Center, NYNew York, New York  10029
New York Presbyterian Hospital - Cornell CampusNew York, New York  10021
Dana-Farber Cancer InstituteBoston, Massachusetts  02115
North Shore University HospitalManhasset, New York  11030
CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.Syracuse, New York  13217
University of Illinois at Chicago Health Sciences CenterChicago, Illinois  60612
University of Nebraska Medical CenterOmaha, Nebraska  68198-3330