Study of MLN8237 in Patients With Advanced Hematological Malignancies

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00697346
First received: June 11, 2008
Last updated: August 20, 2013
Last verified: August 2013

June 11, 2008
August 20, 2013
July 2008
June 2013   (final data collection date for primary outcome measure)
Determine dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of orally administered MLN8237; and to evaluate the pharmacokinetics of MLN8237. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Determine dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of orally administered MLN8237, evaluate pharmacokinetics and potential effect of MLN8237 exposure on Aurora A kinase inhibition in blood leukocytes. [ Time Frame: Duration of therapy ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00697346 on ClinicalTrials.gov Archive Site
  • To determine if MLN8237 has antitumor activity as measured by tumor response. [ Time Frame: Evaluations will be repeated after every 2 cycles of MLN8237 have been completed for up to 12 months ] [ Designated as safety issue: No ]
  • To evaluate the potential effect of MLN8237 exposure on Aurora A kinase inhibition in blood leukocytes [ Time Frame: Before and during the first cycle of treatment ] [ Designated as safety issue: No ]
To determine if MLN8237 has antitumor activity as measured by tumor response. [ Time Frame: Evaluations will be repeated after every 2 cycles of MLN8237 have been completed for up to 12 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Study of MLN8237 in Patients With Advanced Hematological Malignancies
An Open-label, Phase 1 Study of MLN8237, a Novel Aurora A Kinase Inhibitor, in Patients With Advanced Hematological Malignancies

This is an open-label, multicenter, phase 1 study of MLN8237 in subjects with advanced hematological malignancies for whom there are limited standard treatment options.

Not Provided
Interventional
Phase 1
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • B-cell Follicular Lymphoma
  • B-cell Marginal Zone Lymphoma
  • Diffuse Large B-cell Lymphoma
  • B-cell Mantle Cell Lymphoma
  • B-cell Small Lymphocytic Lymphoma (SLL)
  • B-Cell Chronic Lymphocytic Leukemia (B-CLL)
  • Multiple Myeloma
  • Waldenstrom's Macroglobulinemia
  • Noncutaneous Peripheral T-cell Lymphoma Not Otherwise Specified (PTCL-NOS)
  • Angioimmunoblastic T-cell Lymphoma (AITL)
  • Anaplastic Large Cell Lymphoma
  • Enteropathy Associated T-cell Lymphoma (EATCL)
  • NK Lymphoma (NKL)
Drug: MLN8237

MLN8237 administered twice daily (BID) on Days 1-7 of each cycle. The planned rest period is 14 days in length.

Number of Cycles: until progression or unacceptable toxicity, up to 12 months unless clinical benefit supports continued therapy.

Experimental: 1
MLN8237
Intervention: Drug: MLN8237
Kelly KR, Shea TC, Goy A, Berdeja JG, Reeder CB, McDonagh KT, Zhou X, Danaee H, Liu H, Ecsedy JA, Niu H, Benaim E, Iyer SP. Phase I study of MLN8237--investigational Aurora A kinase inhibitor--in relapsed/refractory multiple myeloma, non-Hodgkin lymphoma and chronic lymphocytic leukemia. Invest New Drugs. 2014 Jun;32(3):489-99. doi: 10.1007/s10637-013-0050-9. Epub 2013 Dec 20.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
58
June 2013
June 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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:

    • B-cell Follicular lymphoma
    • B-cell Marginal zone lymphoma
    • Diffuse large B-cell lymphoma
    • B-cell Mantle cell lymphoma
    • B-cell Small lymphocytic lymphoma (SLL)
    • B-Cell Chronic lymphocytic leukemia (B-CLL)
    • Multiple myeloma
    • Waldenstrom's macroglobulinemia
    • Noncutaneous peripheral T-cell lymphoma not otherwise specified (PTCL-NOS)
    • Angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma, enteropathy associated T-cell lymphoma (EATCL), NK lymphoma (NKL)
  • Subjects with 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.
  • Aged 18 years or older
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
  • Radiographically or clinically evaluable disease for Part 1 of this study and measurable disease for Part 2 of this study
  • Suitable venous access for the conduct of blood sampling for MLN8237 PK
  • Recovered from the reversible effects of prior antineoplastic treatment (with the exception of alopecia and Grade 1 neuropathy)

Exclusion Criteria:

  • Pregnant or lactating
  • Treatment with clinically significant enzyme inducers within 14 days prior to the first dose of MLN8237 as specified in the protocol
  • Prior allogeneic bone marrow (or other organ) transplantation
  • Newly diagnosed or uncontrolled cancer-related CNS disease
  • 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 or Rituximab, alemtuzumab (Campath®), or other unconjugated therapeutic antibody (21 days if clear evidence of progressive disease)
  • Treatment with radioimmunoconjugates or toxin immunoconjugates such as ibritumomab tiuxetan (Zevalin™), or tositumomab (Bexxar®) within 56 days preceding the first dose of study treatment
  • Antineoplastic treatment with glucocorticoids within 21 days preceding the first dose of study treatment
  • Radiotherapy involving <25% of the hematopoietically active bone marrow within 21 days preceding first dose of study treatment
  • Radiotherapy involving ≥25% of the hematopoietically active bone marrow within 42 days preceding first dose of study treatment
  • Inability to swallow capsules or 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.
  • History of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness such as severe chronic obstructive pulmonary disease
  • 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.
  • Patients who fail to meet laboratory values as specified in the protocol during the screening period
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00697346
C14003
No
Millennium Pharmaceuticals, Inc.
Millennium Pharmaceuticals, Inc.
Not Provided
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
Millennium Pharmaceuticals, Inc.
August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP