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Study Summary
No. 2008-0278:.......Lymphoma......Nathan Fowler......Lymphoma/Myeloma
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Study Summary Title
Study Summary
Number:
2008-0278
Study Title:An Open-Label, Phase 1 Study of MLN8237, a Novel Aurora A Kinase Inhibitor, in Patients with Advanced Hematological Malignancies
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Physician New Patient Referral
Name:Nathan FowlerPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Lymphoma/MyelomaReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2860
Contact us about clinical trials
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General Information
Disease Group:LymphomaSupported By:Millennium Pharmaceuticals, Inc. in partnership with Johnson & Johnson
Phase of Study:Phase IReturn
Visit:
Screening visit, Cycle 1, Days 1, 2, 8, 15, 22, 23, 24, 25, & 26. Cycle 2, Days
1, 8, 11, 15, 18, 22, 25. End of Treatment and End of Study/ Follow-up.
Treatment
Agents:
MLN8237Home Care:n/a
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
n/a
Description/
Intervention:
The goal of this clinical research study is to find the highest safe dose of
MLN8237 that can be given to patients with a hematological cancer. How much
drug is absorbed into the bloodstream and then taken out of the body, how the
drug affects genes and proteins that are involved in cancer, and what side
effects the drug causes will also be studied.
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Study Objectives / Outcomes
Primary Objectives
The primary objectives are:

• To determine the DLT and MTD of orally administered MLN8237
• To describe the pharmacokinetics (PK) of MLN8237
• To evaluate the potential effect of MLN8237 exposure on Aurora A kinase
inhibition in blood leukocytes

Secondary Objectives
The secondary objectives are:

• To determine if MLN8237 has antitumor activity as measured by tumor
response
• To explore the relationship between polymorphic variations in the
UDP-glucuronosyltransferase gene UGT1A1 and exposure to MLN8237
• To assess biomarkers in relation to clinical response in banked tumor
specimens including, but not limited to, Aurora A kinase protein expression
levels and gene amplification
• To assess 2 common polymorphic variants in the Aurora A kinase gene
(Phe31Ile and Val57Ile) thought to potentially influence tumorigenesis
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Study Status Information
Study Activation / Registration Date:10/03/2008
IRB Review and Approval Date:07/07/2008
Study Type:Phase I
Recruitment Status:Open
Projected Accrual:Up to 57 patients
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Relapsed or refractory disease and a histologically or cytologically confirmed hematological malignancy of the following type for which standard curative treatment does not exist or is no longer effective: follicular lymphoma; marginal zone lymphomas; diffuse large B-cell lymphoma; mantle cell lymphoma; small lymphocytic leukemia (SLL); chronic lymphocytic leukemia (CLL); multiple myeloma; Waldenstrom's macroglobulinemia (Continued in Inclusion #2)

2) (Continued from Inclusion #1) Subjects with a diagnosis of diffuse large B-cell lymphoma must have failed, be ineligible for, or have refused an autologous stem cell transplant. There is no restriction regarding the maximum number of prior regimens.

3) Aged 18 years or older

4) Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

5) Radiographically or clinically evaluable disease for Part 1 of this study and measurable disease for Part 2 of this study

6) Suitable venous access for the conduct of blood sampling for MLN8237 PK

7) Recovered from the reversible effects of prior antineoplastic treatment (with the exception of alopecia and Grade 1 neuropathy)

8) Male subjects must use an appropriate method of barrier contraception (eg, condoms), inform any sexual partners that they must also use a reliable method of contraception (eg, a hormonal contraceptive, an intrauterine device, diaphragm with spermicide, or abstinence), and refrain from blood and semen donation during the study and for 90 days after the last dose of study treatment.

9) Female subjects must be postmenopausal, surgically sterilized, or willing to use reliable methods of birth control (eg, a hormonal contraceptive, an intrauterine device, diaphragm with spermicide, or abstinence) and refrain from blood donation during the study and for 90 days after the last dose of study treatment. Female subjects must have a negative pregnancy test prior to receiving MLN8237.

10) Willing and able to give written informed consent before the conduct of any study-related procedure that is not part of normal medical care and willing to comply with the protocol.

Exclusion Criteria:1) Pregnant or lactating

2) Prior allogeneic bone marrow (or other organ) transplantation

3) Systemic antineoplastic treatment within 21 days preceding the first dose of study treatment. Exceptions requiring a 42-day recovery period from last treatment include: Nitrosoureas, mitomycin C; Rituximab, alemtuzumab (Campath®), or other unconjugated therapeutic antibody (21 days if clear evidence of progressive disease)

4) Treatment with radioimmunoconjugates or toxin immunoconjugates such as ibritumomab tiuxetan (Zevalin), or tositumomab (Bexxar®) within 56 days preceding the first dose of study treatment

5) Antineoplastic treatment with glucocorticoids within 21 days preceding the first dose of study treatment

6) Radiotherapy involving <25% of the hematopoietically active bone marrow within 21 days preceding first dose of study treatment

7) Radiotherapy involving >/=25% of the hematopoietically active bone marrow within 42 days preceding first dose of study treatment

8) Major surgery within the 14 days preceding the first dose of study treatment

9) Serious infection within 14 days prior to the first dose of study treatment

10) Life-threatening or uncontrolled medical illness unrelated to cancer

11) Ongoing nausea or vomiting that is Grade 2 or worse in intensity

12) Diarrhea that is Grade 2 or worse in intensity or use of an antimotility agent to control diarrhea to an intensity of Grade 1 or lower level

13) Known GI disease or GI procedures that could interfere with the oral absorption or tolerance of MLN8237. Examples include, but are not limited to, partial gastrectomy, history of small intestine surgery, and celiac disease.

14) History of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness such as severe chronic obstructive pulmonary disease

15) Inability to swallow capsules, or inability or unwillingness to avoid taking anything by mouth except for water and prescribed medications for 2 hours before and 1 hour after each dose of MLN8237

16) Newly diagnosed or uncontrolled cancer-related CNS disease

17) Absolute neutrophil count (ANC) <1,500/mm^3

18) Platelet count <75,000/mm^3

19) Measured or estimated creatinine clearance (Cockcroft-Gault formula) <30 mL/minute

20) Bilirubin >1.5 times the ULN or aspartate transaminase (AST)/alanine transaminase (ALT) >2.5 times the ULN. The AST or ALT level may be elevated up to 5 times the ULN if the elevation can be reasonably attributed to the presence of metastatic disease to liver.

21) Diagnosed or treated for another malignancy within 2 years of first dose, or who were previously diagnosed with another malignancy and have any radiographic or biochemical marker evidence of active disease. In the case of prior prostate cancer treated with radiotherapy, the PSA may be detectable, but must be <1 ng/mL. Subjects with completely resected basal cell carcinoma, squamous cell carcinoma of the skin, or in situ malignancy of any type are not excluded.

22) Abnormalities on 12-lead electrocardiogram (ECG) considered by the investigator to be clinically significant, including but not limited to clinically important QTc prolongation

23) Known or suspected human immunodeficiency virus (HIV) positive or hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection. Testing is not required in the absence of clinical findings or suspicion.

24) Inability to comply with study visits and procedures

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Links
Registration Number: NCT00697346
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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