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A Phase I Study of PS-341 in Patients With Hematologic Malignancies

Phase 1
18 Years
Not Enrolling
Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes

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Trial Information

A Phase I Study of PS-341 in Patients With Hematologic Malignancies

OBJECTIVES: I. Determine the maximum tolerated dose and dose-limiting toxicity of PS-341 in
patients with hematologic malignancies. II. Determine the pharmacodynamics of this drug in
these patients. III. Determine response to this drug in these patients. IV. Determine the
correlation between response of malignancies and proteasome inhibition and apoptosis in
peripheral blood mononuclear cells (PBMC) of these patients. V. Determine the correlation
between therapy toxicity and proteasome inhibition and apoptosis in PBMC of these patients.
VI. Determine the effect of this drug on other molecular markers (i.e., BCL-2 in follicular
lymphoma patients and t9;22/BCR/ABL in chronic lymphocytic leukemia patients). VII.
Determine the correlation between interleukin-6 serum levels in multiple myeloma patients
and drug dosing, toxicity of therapy, extent of protease inhibition, response to therapy,
and apoptosis in PBMC of these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients receive PS-341 IV over 30
minutes on days 1, 4, 8, 11, 15, 18, 22, and 25 followed by a 2-week rest. Treatment repeats
every 6 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6
patients receive escalating doses of PS-341 until the maximum tolerated dose (MTD) is
determined. The MTD is defined as the dose at which 2 of 6 patients experience dose-limiting

PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study.

Inclusion Criteria

DISEASE CHARACTERISTICS: Histologically confirmed hematologic malignancy including: Acute
myeloid leukemia Chronic myelogenous leukemia Acute lymphoblastic leukemia Chronic
lymphocytic leukemia Hodgkin's disease Non-Hodgkin's lymphoma Multiple myeloma
Myelodysplastic syndrome subtypes: Refractory anemia with excess blasts (RAEB) RAEB in
transformation Refractory to standard treatment or no curative therapy available
Measurable disease Not eligible for higher priority study

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At
least 6 weeks Hematopoietic: WBC at least 3,000/mm3 Absolute neutrophil count at least
1,000/mm3 Platelet count at least 50,000/mm3 Hematocrit at least 25% Hepatic: SGOT and
SGPT less than 2.5 times upper limit of normal (ULN) Bilirubin less than 1.5 times ULN
Renal: Creatinine clearance greater than 50 mL/min Cardiovascular: No acute ischemia or
new conduction system abnormalities by EKG No prior myocardial infarction within past 6
months No New York Heart Association class III or IV congestive heart failure Other:
Febrile episodes up to 38.5 degrees C due to tumor fever allowed No concurrent active
infection No grade 1 or greater National Cancer Institute common toxicity criteria No
serious medical or psychiatric condition that would preclude study Not pregnant or nursing
Negative pregnancy test Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 weeks since prior immunotherapy No
concurrent immunotherapy Chemotherapy: At least 4 weeks since prior chemotherapy No other
concurrent chemotherapy Endocrine therapy: Not specified Radiotherapy: At least 4 weeks
since prior radiotherapy No concurrent radiotherapy Surgery: At least 2 weeks since prior
major surgery

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Steven Soignet, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Federal Government

Study ID:




Start Date:

April 2000

Completion Date:

October 2001

Related Keywords:

  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • recurrent adult Hodgkin lymphoma
  • refractory multiple myeloma
  • recurrent adult acute myeloid leukemia
  • recurrent adult acute lymphoblastic leukemia
  • relapsing chronic myelogenous leukemia
  • refractory chronic lymphocytic leukemia
  • refractory anemia with excess blasts
  • refractory anemia with excess blasts in transformation
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • recurrent adult diffuse mixed cell lymphoma
  • recurrent adult diffuse large cell lymphoma
  • recurrent adult immunoblastic large cell lymphoma
  • recurrent adult lymphoblastic lymphoma
  • recurrent adult Burkitt lymphoma
  • previously treated myelodysplastic syndromes
  • recurrent mantle cell lymphoma
  • recurrent marginal zone lymphoma
  • recurrent small lymphocytic lymphoma
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • splenic marginal zone lymphoma
  • Neoplasms
  • Leukemia
  • Lymphoma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myelodysplastic Syndromes
  • Preleukemia



Memorial Sloan-Kettering Cancer Center New York, New York  10021