Study of MLN8237 in Patients With Advanced Hematological Malignancies - Full Text View

Sponsor:	Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):	Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT00697346

Purpose

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.

Condition	Intervention	Phase
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	Phase I

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	An Open-label, Phase 1 Study of MLN8237, a Novel Aurora A Kinase Inhibitor, in Patients With Advanced Hematological Malignancies

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Acute Lymphocytic Leukemia Cancer Chronic Lymphocytic Leukemia Leukemia Lymphoma Multiple Myeloma

U.S. FDA Resources

Further study details as provided by Millennium Pharmaceuticals, Inc.:

Primary Outcome Measures:

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 ]

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	97
Study Start Date:	July 2008
Estimated Study Completion Date:	January 2013
Estimated Primary Completion Date:	November 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 MLN8237	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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00697346

Locations

United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203

Sponsors and Collaborators

Millennium Pharmaceuticals, Inc.

Investigators

Study Director:

Medical Monitor

Millennium Pharmaceuticals, Inc.

More Information

No publications provided

Responsible Party:	Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT00697346 History of Changes
Other Study ID Numbers:	C14003
Study First Received:	June 11, 2008
Last Updated:	December 7, 2011
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Immunoblastic Lymphadenopathy
Intestinal Diseases
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Lymphoma, Follicular
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Non-Hodgkin
Waldenstrom Macroglobulinemia
Multiple Myeloma
Neoplasms, Plasma Cell
Lymphoma, B-Cell
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral

Lymphoma, Large-Cell, Anaplastic
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Mantle-Cell
Hematologic Neoplasms
Enteropathy-Associated T-Cell Lymphoma
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Gastrointestinal Diseases
Digestive System Diseases
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Hemostatic Disorders

ClinicalTrials.gov processed this record on February 09, 2012