Alisertib and Romidepsin in Treating Patients With Relapsed or Refractory B-Cell or T-Cell Lymphomas

NCT01897012 | Completed Phase 1 FDA Drug

• 7 other identifiers: NCI-2013-01272TX0352012-06029342P30CA016672U01CA062461UM1CA186688
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of alisertib and romidepsin in treating patients with B-cell or T-cell lymphomas that have returned after a period of improvement (relapsed) or have not responded to treatment (refractory). Alisertib and romidepsin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Conditions

MYC Positive; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements; Recurrent Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements; Refractory Hodgkin Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events as graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (utilized for adverse event reporting beginning April 1, 2018)

  Up to 4 weeks post-treatment

• Maximum tolerated dose graded according to NCI CTCAE version 5.0

  Maximum tolerated dose is defined as the highest dose level at which 6 patients have been treated with fewer than 2 instances of dose-limiting toxicities.

  Up to 28 days

Secondary Outcomes (2)

• Overall response rate

  Up to 4 weeks post-treatment

• Complete response

  Up to 4 weeks post-treatment

Other Outcomes (2)

• Aurora A kinase expression intensity, assessed by immunohistochemistry

  Baseline

• Change in gene expression profiles

  Baseline to up to 28 days (course 1)

Study Arms (1)

Treatment (alisertib, romidepsin)

EXPERIMENTAL

Patients receive alisertib PO BID on days 1-7 (dose levels 1-4) or days 1-3, 8-10, and 15-17 (dose levels 5-8). Patients also receive romidepsin IV over 4 hours on days 1 and 8 (dose levels 1-4) or 2, 9, and 16 (dose levels 5-8). Treatment repeats every 21 days (dose levels 1-4) or 28 days (dose levels 5-8) for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Drug: Alisertib; Other: Laboratory Biomarker Analysis; Drug: Romidepsin

Interventions

Alisertib DRUG

Given PO

Also known as: Aurora A Kinase Inhibitor MLN8237, MLN-8237, MLN8237

Treatment (alisertib, romidepsin)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (alisertib, romidepsin)

Romidepsin DRUG

Given IV

Also known as: Antibiotic FR 901228, Depsipeptide, FK228, FR901228, Istodax, N-[(3S,4E)-3-Hydroxy-7-mercapto-1-oxo-4-heptenyl]-D-valyl-D-cysteinyl-(2Z)-2-amino-2-butenoyl-L-valine, (4->1) Lactone, Cyclic

Treatment (alisertib, romidepsin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed Hodgkin lymphoma, Burkitt's lymphoma, double-hit lymphoma, other c-Myc positive B-cell lymphoma, diffuse large-B cell lymphoma including those patients with history of transformed follicular lymphoma, mantle cell lymphoma, or peripheral T-cell lymphoma
• Patients must have at least one 1.5 cm bidimensional measurable lesion
• Relapsed or refractory after at least 1 front-line therapy
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Life expectancy of greater than 12 weeks
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 75,000/mcL
• Direct bilirubin =\< 1 mg/dL
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal
• Creatinine =\< 2 x institutional upper limits of normal
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 4 months after completion of MLN8237 plus romidepsin administration; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of MLN8237 plus romidepsin administration
• Ability to understand and the willingness to sign a written informed consent document
• According to current guidelines, patients must be able to take oral medication and to maintain a fast as required for 2 hours before and 1 hour after MLN8237 administration; these guidelines may change pending results from an ongoing food effects study

You may not qualify if:

• Patients who have had chemotherapy, radiation therapy, or other investigational agents within 3 weeks prior to entering study, 6 weeks for nitrosoureas or mitomycin
• Patients with known brain metastases should be excluded from this clinical trial
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to MLN8237, including but not limited to established allergic reaction to benzodiazepines, or romidepsin; agents that alter gastric pH may change MLN8237 absorption are not permitted; proton pump inhibitors need to be stopped 4 days prior to the first dose of MLN8237; histamine-2 (H2) receptor antagonists are not permitted from the day prior (day -1) through to the end of MLN8237 dosing; antacid preparations are not permitted for 2 hours before or 2 hours after administration of MLN8237
• Co-administration of enzyme-inducing antiepileptic drugs, rifampin, rifabutin, rifapentine, or St. John's wort is not permitted; concurrent bisphosphonate therapy is allowed if it was started before study entry and is maintained at recommended dosing intervals; bisphosphonate therapy may not be initiated after study entry
• Any serious active disease or co-morbid condition, which in the opinion of the principal investigator, will interfere with the safety or compliance of the trial
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with MLN8237 and/or romidepsin
• Ejection fraction (EF) \< 40% or myocardial infarction (MI) within the past 3 months; known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen; or any conditions that could result in excessive toxicity associated with the benzodiazepine-like effects of MLN8237
• Requirement for constant administration of proton pump inhibitor, H2 antagonist, or pancreatic enzymes; intermittent uses of antacids or H2 antagonists are allowed
• Inability to swallow oral medication or to maintain a fast as required for 2 hours before and 1 hour after MLN8237 administration or any condition that would modify small bowel absorption of oral medications, including malabsorption, or resection of pancreas or upper bowel; treatment with clinically significant enzyme inducers, such as the enzyme-inducing antiepileptic drugs phenytoin, carbamazepine, oxcarbazepine, primidone or phenobarbital, or rifampin, rifabutin, rifapentine, or St. John's wort within 14 days prior to the first dose of MLN8237 and during the study; patients must be cautiously co-medicated with agents that cause corrected QT interval (QTc) prolongation and agents that are strong or moderate enzyme inhibitors during the study

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Lymphoma, B-Cell; Burkitt Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Hodgkin Disease; Lymphoma, Mantle-Cell; Lymphoma, T-Cell

Interventions

MLN 8237; romidepsin; Depsipeptides; Lactones

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Organic Chemicals

Study Officials

• Hun Lee

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2013
• First Posted: July 11, 2013
• Study Start: July 17, 2013
• Primary Completion: October 31, 2018
• Study Completion: November 30, 2018
• Last Updated: January 28, 2019

Record last verified: 2019-01

Locations

US (1)