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


Phase 1
18 Years
N/A
Not Enrolling
Both
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

Thank you

Trial Information

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


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.


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

MTD as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0

Outcome Time Frame:

21 days

Safety Issue:

Yes

Principal Investigator

Francis Giles

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02633

NCT ID:

NCT00095797

Start Date:

October 2004

Completion Date:

Related Keywords:

  • 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
  • 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

Name

Location
M D Anderson Cancer Center Houston, Texas  77030