XK469R in Treating Patients With Refractory Hematologic Cancer

National Cancer Institute (NCI)

Status and phase: Completed; Phase 1

Conditions: Refractory Anemia With Excess Blasts in Transformation; Adult Acute Basophilic Leukemia; Untreated Adult Acute Myeloid Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Pure Erythroid Leukemia (M6b); Previously Treated Myelodysplastic Syndromes; Relapsing Chronic Myelogenous Leukemia; Adult Acute Monoblastic Leukemia (M5a); Adult Acute Eosinophilic Leukemia; Adult Acute Myelomonocytic Leukemia (M4); Refractory Anemia With Excess Blasts; Refractory Chronic Lymphocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Adult Acute Myeloblastic Leukemia Without Maturation (M1); Blastic Phase Chronic Myelogenous Leukemia; Stage III Chronic Lymphocytic Leukemia; Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monocytic Leukemia (M5b); Chronic Myelomonocytic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Erythroleukemia (M6a); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; de Novo Myelodysplastic Syndromes; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Secondary Myelodysplastic Syndromes; Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloblastic Leukemia With Maturation (M2); Stage IV Chronic Lymphocytic Leukemia; Recurrent Adult Acute Myeloid Leukemia

Treatments: Other: laboratory biomarker analysis; Drug: R(+)XK469; Other: pharmacological study

Study type: Interventional

Funder types: NIH

Identifiers

NCT00095797

U10CA62461 (Other Grant/Funding Number)

MDA-2004-0154

CDR0000393836 (Registry Identifier)

NCI-2012-02633

Details and patient eligibility

About

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

Full 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.

Enrollment: 60 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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60 participants in 1 patient group

Treatment (XK469R)

Experimental group

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.

Treatment:

Other: pharmacological study

Drug: R(+)XK469

Other: laboratory biomarker analysis