Brief Title
Study of MLN8237 in Participants With Advanced Hematological Malignancies
Official Title
An Open-label, Phase 1 Study of MLN8237, a Novel Aurora A Kinase Inhibitor, in Patients With Advanced Hematological Malignancies
Brief Summary
This is an open-label, multicenter, phase 1 study of MLN8237 in participants with advanced
hematological malignancies for whom there are limited standard treatment options.
Detailed Description
The drug being tested in this study is called alisertib. Alisertib is being tested to treat
people who have advanced hematological malignancies. This study determined the dose-limiting
toxicity, maximum tolerated dose, safety and pharmacokinetics (how the drug moves through the
body) for alisertib when given once or twice a day for 7 to 21 days.
This open label study enrolled 58 patients. Participants were enrolled in one of 3 treatment
groups:
- Part 1: Powder-in-Capsule (PIC) Dose Escalation (alisertib 25 mg PIC, orally twice daily
[BID] on Day 1 [loading dose] and then alisertib 25 or 35 mg PIC once daily [QD] for 21
days (D), or alisertib 35, 45, 65 or 90 mg PIC, orally, QD for 14D) in 28-day cycles
- Part 1: Enteric-coated Tablet (ECT) Dose Escalation (alisertib 40 mg, ECT, orally, QD
for 14D or alisertib 30, 40 or 50 mg, orally, BID for 7D) in 28-day cycles
- Part 2: Participants with Peripheral T-cell Lymphoma (PTCL) (alisertib 50 mg ECT,
orally, BID for 7D) in 21-day cycles
All participants received treatment for 12 months or until their disease progressed or they
experienced unacceptable alisertib-related toxicity. This multi-center trial was conducted in
the United States. The overall time to participate in this study was 422 days. Participants
made multiple visits to the clinic, including a final visit 30 days after receiving their
last dose of alisertib for a follow-up assessment.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Number of Participants With Dose-Limiting Toxicity (DLT)
Secondary Outcome
Best Overall Response Rate Based on Investigator's Assessment
Condition
B-cell Follicular Lymphoma
Intervention
Alisertib
Study Arms / Comparison Groups
Part 1: PIC Dose Escalation
Description: Alisertib 25 or 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles or alisertib 35, 45, 65 or 90 mg PIC, orally, (QD for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 14 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose), followed by their respective dosage assignment.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
58
Start Date
July 11, 2008
Completion Date
October 19, 2016
Primary Completion Date
October 1, 2016
Eligibility 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)
- Participants 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 pharmacokinetics
(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 central nervous system (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 gastrointestinal (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.
- Participants who fail to meet laboratory values as specified in the protocol during
the screening period
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Medical Director Clinical Science, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00697346
Organization ID
C14003
Secondary IDs
U1111-1187-1184
Responsible Party
Sponsor
Study Sponsor
Millennium Pharmaceuticals, Inc.
Study Sponsor
Medical Director Clinical Science, Study Director, Millennium Pharmaceuticals, Inc.
Verification Date
February 2019