XK469R in Treating Patients With Refractory Hematologic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00095797
Recruitment Status : Completed
First Posted : November 9, 2004
Last Update Posted : February 8, 2013
Information provided by (Responsible Party):
National Cancer Institute (NCI)

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

Condition or disease Intervention/treatment Phase
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 Drug: R(+)XK469 Other: pharmacological study Other: laboratory biomarker analysis Phase 1

Detailed Description:


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.


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  (Clinical Trial)
Actual Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of XK469R (NSC 698215) in Patients With Refractory Hematologic Malignancies
Study Start Date : October 2004
Actual Primary Completion Date : March 2007

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.
Drug: R(+)XK469
Given IV
Other Name: XK469

Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Other: laboratory biomarker analysis
Optional correlative studies

Primary Outcome Measures :
  1. MTD as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 [ Time Frame: 21 days ]
  2. 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 Measures :
  1. 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 ]
  2. Candidate genes for XK469R using PCR assay [ Time Frame: At baseline ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00095797

United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Francis Giles M.D. Anderson Cancer Center

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00095797     History of Changes
Other Study ID Numbers: NCI-2012-02633
U10CA62461 ( Other Grant/Funding Number: US NIH Grant/Contract Award Number )
CDR0000393836 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: November 9, 2004    Key Record Dates
Last Update Posted: February 8, 2013
Last Verified: February 2013

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Anemia, Refractory
Blast Crisis
Anemia, Refractory, with Excess of Blasts
Leukemia, Monocytic, Acute
Hypereosinophilic Syndrome
Leukemia, Megakaryoblastic, Acute
Leukemia, Erythroblastic, Acute
Anemia, Aplastic
Leukemia, Basophilic, Acute
Leukemia, Eosinophilic, Acute
Pathologic Processes
Neoplasms by Histologic Type
Hematologic Diseases
Bone Marrow Diseases