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XK469R in Treating Patients With Refractory Hematologic Cancer

Primary Purpose

Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia, Adult Acute Megakaryoblastic Leukemia (M7)

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
R(+)XK469
pharmacological study
laboratory biomarker analysis
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 Basophilic Leukemia

Eligibility Criteria

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

Inclusion Criteria: Diagnosis of 1 of the following relapsed or refractory hematologic malignancies for which all potentially curative therapy options have been exhausted: Acute myeloid leukemia* (AML) (non-M3) Acute lymphoblastic leukemia* Myelodysplastic syndromes*, including the following: Refractory anemia with excess blasts (RAEB) RAEB in transformation Chronic myelomonocytic leukemia in transformation* (CMML-t) with ≥ 10% peripheral blood/bone marrow blasts Chronic myelogenous leukemia in blast crisis* (CML-BC) Chronic lymphocytic leukemia Rai stage III-IV Failed prior fludarabine-based therapy and ≥ 1 other therapy Fludarabine failure defined as failure to achieve partial response or complete response (CR) to at least 1 fludarabine-containing regimen; disease progression while on fludarabine; or disease progression within 6 months of response to fludarabine Not a candidate for autologous or allogeneic stem cell transplantation (SCT) Patients with previously untreated AML, MDS, or CMML-t who are considered inappropriate candidates for, or refused, standard induction chemotherapy due to older age or concurrent medical conditions are eligible No known CNS disease Performance status - ECOG 0-2 See Disease Characteristics Bilirubin < 1.5 times upper limit of normal (ULN) AST and ALT < 5 times ULN Creatinine < 1.5 times ULN No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Not pregnant or nursing Fertile patients must use effective contraception No ongoing or active infection No psychiatric illness or social situation that would preclude study compliance No history of allergic reactions attributed to compounds of similar chemical or biologic composition to XK469R No other uncontrolled illness HIV-positive patients allowed provided CD4 counts are normal with no AIDS-defining disease No prior allogeneic SCT No concurrent prophylactic hematopoietic colony-stimulating factors More than 7 days since prior cytotoxic chemotherapy (except hydroxyurea) More than 7 days since prior radiotherapy No concurrent combination antiretroviral therapy for HIV-positive patients No other concurrent investigational agents No other concurrent anti-leukemia agents No other concurrent anticancer therapy

Sites / Locations

  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (XK469R)

Arm Description

Patients receive XK469R IV over 30-60 minutes on days 1, 3, and 5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

MTD as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Dose-limiting toxicity (DLT) defined as a clinically significant adverse event or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications using CTCAE version 3.0

Secondary Outcome Measures

Pharmacokinetic profile of XK496R
Candidate genes for XK469R using PCR assay

Full Information

First Posted
November 9, 2004
Last Updated
February 7, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00095797
Brief Title
XK469R in Treating Patients With Refractory Hematologic Cancer
Official Title
A Phase I Study of XK469R (NSC 698215) in Patients With Refractory Hematologic Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
February 2013
Overall Recruitment Status
Completed
Study Start Date
October 2004 (undefined)
Primary Completion Date
March 2007 (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 XK469R in treating patients who have refractory hematologic cancer. Drugs used in chemotherapy, such XK469R, work in different ways to stop cancer cells from dividing so they stop growing or die
Detailed Description
PRIMARY OBJECTIVES: I. Determine the dose-limiting toxicity, maximum tolerated dose, and recommended phase II dose of XK469R in patients with refractory hematologic malignancies. II. Determine the pharmacokinetics of this drug in these patients. SECONDARY OBJECTIVES: I. Determine the presence of genetic variations potentially affecting XK469R disposition in patients treated with this drug. OUTLINE: This is an open-label, dose-escalation, multicenter study. Patients receive XK469R IV over 30-60 minutes on days 1, 3, and 5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of XK469R until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which at least 2 of 6 patients experience dose-limiting toxicity. A total of 12 patients receive treatment at the MTD. PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia, Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2), Adult Acute Myeloblastic Leukemia Without Maturation (M1), Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Adult Acute Myelomonocytic Leukemia (M4), Adult Erythroleukemia (M6a), Adult Pure Erythroid Leukemia (M6b), Blastic Phase Chronic Myelogenous Leukemia, Chronic Myelomonocytic Leukemia, de Novo Myelodysplastic Syndromes, 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, Refractory Chronic Lymphocytic Leukemia, Relapsing Chronic Myelogenous Leukemia, Secondary Myelodysplastic Syndromes, Stage III Chronic Lymphocytic Leukemia, Stage IV Chronic Lymphocytic Leukemia, Untreated Adult Acute Myeloid 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
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (XK469R)
Arm Type
Experimental
Arm Description
Patients receive XK469R IV over 30-60 minutes on days 1, 3, and 5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
R(+)XK469
Other Intervention Name(s)
XK469
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
pharmacological study
Other Intervention Name(s)
pharmacological studies
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Optional correlative studies
Primary Outcome Measure Information:
Title
MTD as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Time Frame
21 days
Title
Dose-limiting toxicity (DLT) defined as a clinically significant adverse event or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications using CTCAE version 3.0
Time Frame
21 days
Secondary Outcome Measure Information:
Title
Pharmacokinetic profile of XK496R
Time Frame
At baseline, at 15 and 30 minutes, and at 1, 2, 4, 6, 8, and 24 hours (of days 1-2), and at days 3 and 5
Title
Candidate genes for XK469R using PCR assay
Time Frame
At baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of 1 of the following relapsed or refractory hematologic malignancies for which all potentially curative therapy options have been exhausted: Acute myeloid leukemia* (AML) (non-M3) Acute lymphoblastic leukemia* Myelodysplastic syndromes*, including the following: Refractory anemia with excess blasts (RAEB) RAEB in transformation Chronic myelomonocytic leukemia in transformation* (CMML-t) with ≥ 10% peripheral blood/bone marrow blasts Chronic myelogenous leukemia in blast crisis* (CML-BC) Chronic lymphocytic leukemia Rai stage III-IV Failed prior fludarabine-based therapy and ≥ 1 other therapy Fludarabine failure defined as failure to achieve partial response or complete response (CR) to at least 1 fludarabine-containing regimen; disease progression while on fludarabine; or disease progression within 6 months of response to fludarabine Not a candidate for autologous or allogeneic stem cell transplantation (SCT) Patients with previously untreated AML, MDS, or CMML-t who are considered inappropriate candidates for, or refused, standard induction chemotherapy due to older age or concurrent medical conditions are eligible No known CNS disease Performance status - ECOG 0-2 See Disease Characteristics Bilirubin < 1.5 times upper limit of normal (ULN) AST and ALT < 5 times ULN Creatinine < 1.5 times ULN No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Not pregnant or nursing Fertile patients must use effective contraception No ongoing or active infection No psychiatric illness or social situation that would preclude study compliance No history of allergic reactions attributed to compounds of similar chemical or biologic composition to XK469R No other uncontrolled illness HIV-positive patients allowed provided CD4 counts are normal with no AIDS-defining disease No prior allogeneic SCT No concurrent prophylactic hematopoietic colony-stimulating factors More than 7 days since prior cytotoxic chemotherapy (except hydroxyurea) More than 7 days since prior radiotherapy No concurrent combination antiretroviral therapy for HIV-positive patients No other concurrent investigational agents No other concurrent anti-leukemia agents No other concurrent anticancer therapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Francis Giles
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

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XK469R in Treating Patients With Refractory Hematologic Cancer

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