Study of MLN8237 in Participants With Advanced Hematological Malignancies

NCT ID: NCT00697346

Last Updated: 2019-05-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-11
• Study Completion Date: 2016-10-19

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.

Conditions

B-cell Follicular Lymphoma; B-cell Marginal Zone Lymphoma; Diffuse Large B-cell Lymphoma; B-cell Mantle Cell Lymphoma; B-cell Small Lymphocytic Lymphoma; B-Cell Chronic Lymphocytic Leukemia; Multiple Myeloma; Waldenstrom's Macroglobulinemia; Noncutaneous Peripheral T-cell Lymphoma Not Otherwise Specified; Angioimmunoblastic T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Enteropathy Associated T-cell Lymphoma; NK Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Part 1: PIC Dose Escalation

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.

Group Type: EXPERIMENTAL

Alisertib

Intervention Type: DRUG

Alisertib (MLN8237) PIC or ECT

Part 1: ECT Dose Escalation

Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles, or alisertib 30, 40 or 50 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).

Group Type: EXPERIMENTAL

Alisertib

Intervention Type: DRUG

Alisertib (MLN8237) PIC or ECT

Part 2: PTCL

Participants with peripheral T-cell lymphoma (PTCL) received alisertib 50 mg ECT, orally, BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).

Group Type: EXPERIMENTAL

Alisertib

Intervention Type: DRUG

Alisertib (MLN8237) PIC or ECT

Interventions

Alisertib

Alisertib (MLN8237) PIC or ECT

Intervention Type: DRUG

Other Intervention Names

MLN8237

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director Clinical Science

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

Scottsdale, Arizona, United States

Lexington, Kentucky, United States

Baltimore, Maryland, United States

Omaha, Nebraska, United States

Hackensack, New Jersey, United States

Buffalo, New York, United States

Chapel Hill, North Carolina, United States

Nashville, Tennessee, United States

Houston, Texas, United States

San Antonio, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 24352795 (View on PubMed)

Other Identifiers

U1111-1187-1184

Identifier Type: REGISTRY

Identifier Source: secondary_id

C14003

Identifier Type: -

Identifier Source: org_study_id