XK469R in Treating Patients With Refractory Hematologic Cancer

Phase 1

Completed

• Conditions: 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)
• Interventions: Drug: R(+)XK469; Other: pharmacological study; Other: laboratory biomarker analysis

• Registration Number: NCT00095797
• Lead Sponsor: 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

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 Timeline

• Study Start: 2004-10
• Study First Submitted QC: 2004-11-08
• Study First Submitted: 2004-11-09
• Study First Posted: 2004-11-09
• Primary Completion: 2007-03
• Status Verified: 2013-02
• Last Update Submitted: 2013-02-07
• Last Update Posted: 2013-02-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (XK469R)	R(+)XK469	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.
Treatment (XK469R)	pharmacological 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.
Treatment (XK469R)	laboratory biomarker analysis	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.

Primary Outcome Measures

Name	Time	Method
MTD as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0	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	21 days

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic profile of XK496R	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	At baseline

Trial Locations

Locations (1)

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States