Phase I/II Study of Plerixafor and Clofarabine in Previously Untreated Older (>/=60 years) Adult Patients with Acute Myelogenous Leukemia (AML) with two or more unfavorable prognostic factors for Whom Standard Induction Chemotherapy is Unlikely to be of Benefit
Jan A. Burger
The goal of Part 1 of this clinical research study is to learn about the safety of the combination of plerixafor and clofarabine when given to patients with previously untreated AML who are at least 60 years old. The goal of Part 2 of this study is to learn if the combination of plerixafor and clofarabine can help to control previously untreated AML in patients who are at least 60 years old.
Disease Group: Leukemia
Treatment Agent: Clofarabine,Plerixafor
Treatment Location: Only at MD Anderson
Estimatated Length of Stay in Houston: Patients are required to stay in the Houston area for at least 4 weeks during ;course 1. Longer stay may be required as judged by the treating physician. ;There is a maximum of 6 cycles over approximately 5 months.
Sponsor: Genzyme Corporation
Return Visit: Outpatient visits at least weekly until CR, non-response, or resolution of toxicities. Return to MDACC thereafter every 3-6 months during the first year and then every 6-12 months as long as on study.
Home Care: As required.
The primary objective in the Phase 1 portion of the study is to assess the safety of the combination of Plerixafor with Clofarabine in previously untreated older (>/= 60 years) adult patients with acute myelogenous leukemia (AML) with two or more unfavorable prognostic factors for whom standard induction chemotherapy is unlikely to be of benefit. The primary objective in the Phase 2 portion of the study to assess whether the combination of Plerixafor with Clofarabine in previously untreated older (>/= 60 years) adult patients with acute myelogenous leukemia (AML) with two or more unfavorable prognostic factors demonstrates sufficient activity (as assessed by the overall response, OR = CR + PR) to warrant further study. Secondary Objectives • To assess the duration of remission. • To evaluate disease-free survival (DFS). • To evaluate overall survival (OS). • To assess the 30-day mortality rate (ie, rate of deaths occurring between Day 1 and Day 30 of the Induction Cycle. • To determine the efficacy of Plerixafor in mobilizing AML cells and defined AML cell subsets to the peripheral blood in correlative laboratory studies.
IRB Review and Approval Date: 08/05/2010
Recruitment Status: Not Accepting
Projected Accrual: N/A
1) Age >/= 60 years
2) Diagnosis of untreated AML (de novo, secondary, or with an antecedent hematologic disorder [AHD]) according to the World Health Organization (WHO) criteria
3) Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
4) At least 2 of the following adverse prognostic factors: Age >/= 70 years; or AHD; or ECOG performance status of = 2; or intermediate or unfavorable (ie, adverse) karyotype defined as any cytogenetic profile except the presence of any of the following: t(8;21)(q22;q22), inv(16)(p13q22) or t(16;16)(p13;q22), t(15;17)(q22;q12) and variants.
5) Provide signed, written informed consent.
6) Be able to comply with study procedures and follow-up examinations.
7) Adequate renal and hepatic function as indicated by all of the following: Total bilirubin </=1.5 x institutional Upper Limit of Normal (ULN); an AST or ALT </=2.5 x ULN; and an estimated creatinine clearance (CrCl) of > 50 mL/min, as calculated by the Cockroft-Gault equation.
8) Adequate cardiac function as measured by at least 1 of the following: Left ventricular ejection fraction (LVEF) >/=40% on multigated acquisition (MUGA) scan or similar radionuclide angiographic scan; or Left ventricular fractional fractional shortening >/=22% on echocardiography exam; or LVEF >/=40% on echocardiography exam.
9) Women of child-bearing potential (WOCBP) must agree to use adequate birth control through the end of the last treatment visit. WOCBP is a women who has not been naturally postmenopausal for at least 12 consecutive months or who had not undergone previous surgical sterilization.
1) Diagnosis of acute promyelocytic leukemia (APL),
(French-American-British classification M3 or WHO classification of APL
with t(15;17)(q22;q12), (PML/RAR alpha fusion gene and variants).
2) Prior treatment with clofarabine.
3) Prior treatment for AML or an AHD (excluding supportive care, hydroxyurea, hematopoietic cytokines, or lenalidomide [the latter specifically for an AHD only]). Hematopoietic cytokines and lenalidomide must not have been received within 14 days prior to first dose of study drug; hydroxyurea is allowed on study to control WBC counts. If any of the above treatments have been received for AML or an AHD within the permissible time periods, drug-related toxicities must have recovered to Grade 1 or less prior to first dose of study drug.
4) Prior hematopoietic stem cell transplant (HSCT).
5) Prior external beam radiation therapy to the pelvis.
6) Investigational agent received within 30 days prior to the first dose of study drug. If received any investigational agent prior to this time point, drug-related toxicities must have recovered to Grade 1 or less prior to first dose of study drug.
7) Systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
8) Any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver or other organ system that may place the patient at undue risk to undergo therapy with clofarabine.
9) Clinical evidence suggestive of central nervous system (CNS) involvement with leukemia unless a lumbar puncture confirms the absence of leukemic blasts in the cerebrospinal fluid (CSF)
10) Prior positive test for the human immunodeficiency virus (HIV).
11) WBC >50 × 10^9/L; the first 3 patients enrolled on the study will be required to have a WBC of <20 × 10^9/L.
12) Have psychiatric disorders that would interfere with consent, study participation, or follow-up.
13) Have been diagnosed with another malignancy, unless the patient has been disease free for at least 5 years following curative intent therapy, following exceptions: Patients with treated nonmelanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of disease-free duration, if definitive treatment for the condition has been completed or patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values if hormonal therapy has been initiated or radical prostatectomy has been performed.
14) Are pregnant or lactating.
Information and next steps
Phase I/Phase II
Jan A. Burger
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