Text Size

XK469R in Treating Patients With Refractory Hematologic Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00095797
First received: November 9, 2004
Last updated: February 7, 2013
Last verified: February 2013
History of Changes
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of XK469R (NSC 698215) in Patients With Refractory Hematologic Malignancies

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • MTD as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Candidate genes for XK469R using PCR assay [ Time Frame: At baseline ] [ Designated as safety issue: No ]

Enrollment: 60
Study Start Date: October 2004
Primary Completion Date: March 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00095797

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

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00095797     History of Changes
Other Study ID Numbers: NCI-2012-02633, MDA-2004-0154, U10CA62461, CDR0000393836
Study First Received: November 9, 2004
Last Updated: February 7, 2013
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on May 22, 2013