XK469R in Treating Patients With Refractory Hematologic Cancer

February 7, 2013 updated by: National Cancer Institute (NCI)

A Phase I Study of XK469R (NSC 698215) in Patients With Refractory Hematologic Malignancies

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (XK469R)
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.
Other: pharmacological study
Correlative studies
Other Names:
  • pharmacological studies
Other: laboratory biomarker analysis
Optional correlative studies
Drug: R(+)XK469
Given IV
Other Names:
  • XK469

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
MTD as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Time Frame: 21 days
21 days
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
21 days

Secondary Outcome Measures

Outcome Measure
Time Frame
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
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
Candidate genes for XK469R using PCR assay
Time Frame: At baseline
At baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2004

Primary Completion (Actual)

March 1, 2007

Study Registration Dates

First Submitted

November 9, 2004

First Submitted That Met QC Criteria

November 8, 2004

First Posted (Estimate)

November 9, 2004

Study Record Updates

Last Update Posted (Estimate)

February 8, 2013

Last Update Submitted That Met QC Criteria

February 7, 2013

Last Verified

February 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-02633
  • MDA-2004-0154
  • U10CA62461 (Other Grant/Funding Number: US NIH Grant/Contract Award Number)
  • CDR0000393836 (Registry Identifier: PDQ (Physician Data Query))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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