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PS-341 in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia in Blast Phase, or Myelodysplastic Syndrome

Primary Purpose

Adult Acute Promyelocytic Leukemia (M3), Blastic Phase Chronic Myelogenous Leukemia, Previously Treated Myelodysplastic Syndromes

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
bortezomib
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Acute Promyelocytic Leukemia (M3)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: AML, ALL, or high-risk MDS (R-AEB or RAEB-t) that has: Not responded (no CR) to initial induction chemotherapy, or Recurred after an initial CR of < 1 year, or Recurred after an initial CR of > 1 year and failed to respond to an initial re-induction attempt, or Recurred more than once, OR Chronic myeloid leukemia in myeloid blast phase Patients with CML blast phase may receive PS-341 as their first therapy for blast phase or after failing other treatments for blast phase Patients with refractory or relapsed acute promyelocytic leukemia are eligible provided they have failed an ATRA-containing regimen Patients who are likely to benefit from allogeneic bone marrow transplantation (i.e., age < 60 years of physiological age with histocompatible donor) should be excluded from this study unless such therapy is not feasible ECOG performance status =< 52 (Karnofsky >= 50%) Total bilirubin < 1.6 mg/ml ALT or AST =< 2.5 times the institutional upper limit of normal Creatinine < 1.6 mg/ml or creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal Patients must have been off chemotherapy for 2 weeks prior to entering this study and recovered from the toxic effects of that therapy; use of hydroxyurea on patients with rapidly proliferative disease (i.e., absolute peripheral blood blast count >= 5 x 10^9/L, and increasing by >= 1 x 10^9/L/24 hrs) is allowed up to 24 hours prior to the start of therapy with PS-341 The effects of PS-341 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Because the potential risk of toxicity in nursing infants secondary to PS-341 treatment of the mother is unknown but may be harmful, breastfeeding should be discontinued if the mother is treated with PS-341 Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Patients undergoing therapy with other investigational agents Patients with known brain metastases or CNS disease should be excluded from this clinical trail because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other toxicities Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, or unstable angina pectoris, or cardiac arrhythmia HIV-positive patients receiving, anti-retroviral thearpy (HAART) are excluded from the study because of possible pharmacokinetic interactions; appropriate studies will be undertaken in patients receiving, HAART therapy when indicated

Sites / Locations

  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (bortezomib)

Arm Description

Patients receive PS-341 IV bolus twice weekly for 4 weeks followed by 2 weeks of rest. Treatment continues for a maximum of 12 courses in the absence of unacceptable toxicity or disease progression.

Outcomes

Primary Outcome Measures

The occurrence of greater or equal grade 3 toxicity
Graded using the NCI CTC version 2.0.

Secondary Outcome Measures

Full Information

First Posted
April 6, 2000
Last Updated
January 22, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00005064
Brief Title
PS-341 in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia in Blast Phase, or Myelodysplastic Syndrome
Official Title
Phase I Study of PS-341 in Acute Myeloid Leukemias, Myelodysplastic Syndromes and Chronic Myeloid Leukemia in Blast Phase
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
February 2000 (undefined)
Primary Completion Date
October 2002 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
Phase I trial to study the effectiveness of PS-341 in treating patients who have refractory or relapsed acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia in blast phase, or myelodysplastic syndrome. PS-341 may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth
Detailed Description
OBJECTIVES: I. Determine the maximum tolerated dose of PS-341 in patients with refractory or relapsed acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia in blast phase. II. Assess the plasma pharmacology of this drug, its ability to inhibit proteasome function and to accelerate apoptosis in circulating blasts in this patient population. III. Assess the antileukemic effects of this drug in these patients. OUTLINE: This is a dose-escalation study. Patients receive PS-341 IV bolus twice weekly for 4 weeks followed by 2 weeks of rest. Treatment continues for a maximum of 12 courses in the absence of unacceptable toxicity or disease progression. Cohorts of 2 patients receive escalating doses of PS-341 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose level associated with toxicity probability closest to 0.2 after 30 patients are treated.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult Acute Promyelocytic Leukemia (M3), Blastic Phase Chronic Myelogenous Leukemia, Previously Treated Myelodysplastic Syndromes, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia, Refractory Anemia With Excess Blasts, Refractory Anemia With Excess Blasts in Transformation, Relapsing Chronic Myelogenous Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (bortezomib)
Arm Type
Experimental
Arm Description
Patients receive PS-341 IV bolus twice weekly for 4 weeks followed by 2 weeks of rest. Treatment continues for a maximum of 12 courses in the absence of unacceptable toxicity or disease progression.
Intervention Type
Drug
Intervention Name(s)
bortezomib
Other Intervention Name(s)
LDP 341, MLN341, VELCADE
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
The occurrence of greater or equal grade 3 toxicity
Description
Graded using the NCI CTC version 2.0.
Time Frame
35 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: AML, ALL, or high-risk MDS (R-AEB or RAEB-t) that has: Not responded (no CR) to initial induction chemotherapy, or Recurred after an initial CR of < 1 year, or Recurred after an initial CR of > 1 year and failed to respond to an initial re-induction attempt, or Recurred more than once, OR Chronic myeloid leukemia in myeloid blast phase Patients with CML blast phase may receive PS-341 as their first therapy for blast phase or after failing other treatments for blast phase Patients with refractory or relapsed acute promyelocytic leukemia are eligible provided they have failed an ATRA-containing regimen Patients who are likely to benefit from allogeneic bone marrow transplantation (i.e., age < 60 years of physiological age with histocompatible donor) should be excluded from this study unless such therapy is not feasible ECOG performance status =< 52 (Karnofsky >= 50%) Total bilirubin < 1.6 mg/ml ALT or AST =< 2.5 times the institutional upper limit of normal Creatinine < 1.6 mg/ml or creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal Patients must have been off chemotherapy for 2 weeks prior to entering this study and recovered from the toxic effects of that therapy; use of hydroxyurea on patients with rapidly proliferative disease (i.e., absolute peripheral blood blast count >= 5 x 10^9/L, and increasing by >= 1 x 10^9/L/24 hrs) is allowed up to 24 hours prior to the start of therapy with PS-341 The effects of PS-341 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Because the potential risk of toxicity in nursing infants secondary to PS-341 treatment of the mother is unknown but may be harmful, breastfeeding should be discontinued if the mother is treated with PS-341 Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Patients undergoing therapy with other investigational agents Patients with known brain metastases or CNS disease should be excluded from this clinical trail because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other toxicities Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, or unstable angina pectoris, or cardiac arrhythmia HIV-positive patients receiving, anti-retroviral thearpy (HAART) are excluded from the study because of possible pharmacokinetic interactions; appropriate studies will be undertaken in patients receiving, HAART therapy when indicated
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jorge Cortes
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Learn more about this trial

PS-341 in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia in Blast Phase, or Myelodysplastic Syndrome

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