Plerixafor and Clofarabine in Frontline Treatment of Elderly Patients With Acute Myelogenous Leukemia (AML)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01160354
First received: July 8, 2010
Last updated: May 16, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Acute Myelogenous Leukemia
Drug: Plerixafor
Drug: Clofarabine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Number of Participants in Phase I with First Cycle Dose Limiting Toxicities (DLT) Observed [ Time Frame: First cycle of treatment, i.e. first 4 weeks on study ] [ Designated as safety issue: Yes ]
    Dose limiting toxicity (DLT) consists of participants who developed DLT during maximum tolerated dose (MTD) estimation period or who completed the MTD estimation period without DLTs. DLTs observed during dose escalation used to develop MTD.


Secondary Outcome Measures:
  • Number of Participants with Overall Response during Phase II [ Time Frame: Continuously monitored, assessments at 12 weeks ] [ Designated as safety issue: Yes ]
    Overall response (OR) = Complete Remission (CR) + Partial Remission (PR)


Estimated Enrollment: 66
Study Start Date: August 2010
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Plerixafor + Clofarabine

Phase I: Plerixafor starting at 240 mcg/kg daily subcutaneous (SQ) injection on Days 1-5, 4-6 hours before a 1 hour (+/- 30 minutes) IV administration of Clofarabine.

Phase II: Plerixafor at the highest dose tolerated in Phase I.

Phase I and II: Clofarabine fixed dose of 30 mg/m2/day during Induction cycle (20 mg/m2/day in consolidation cycles).

Drug: Plerixafor
Starting at 240 mcg/kg daily subcutaneous (SQ) injection on Days 1-5, 4-6 hours before a 1 hour (+/- 30 minutes) IV administration of Clofarabine
Other Name: Mobozil
Drug: Clofarabine
Fixed dose of 30 mg/m2/day during Induction cycle (20 mg/m2/day in consolidation cycles).
Other Names:
  • Clofarex
  • Clolar

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  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 Cockcroft -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.

Exclusion Criteria:

  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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01160354

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Genzyme, a Sanofi Company
Investigators
Study Chair: Jan A. Burger, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01160354     History of Changes
Other Study ID Numbers: 2009-0536, NCI-2012-01786
Study First Received: July 8, 2010
Last Updated: May 16, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Leukemia
AML
Clofarabine
Plerixafor
elderly patients
previously untreated
unfavorable prognostic factors

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
JM 3100
Clofarabine
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on October 01, 2014