Phase II Study of TAK228 in Relapsed Lymphoma

NCT02727777 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 2014-0501NCI-2016-00671
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if TAK-228 can help to control relapsed lymphoma. The safety of this drug will also be studied.

Conditions

Lymphoma

Keywords

Lymphoma; Relapsed Lymphoma; MLN0128; Blood sugar; Glucometer; TK228

Outcome Measures

Primary Outcomes (1)

• Response Assessment (RA)

  RA was defined by Lugano Criteria \& based on CT scans obtained at screening \& after completion of every 2 cycles of therapy. Complete Radiographic Response Target Nodes must regress to \<=1.5cm in longest dimension,No extralymphatic sites of disease. PR \>=50% decrease in sum of the product of diameters of up to 6 target measurable nodes and extranodal sites. When a lesion is too small to measure on CT, 5 mmx5mm is assigned. When not visible on CT, assign 0x0 mm. For a node 5mmx5mm use actual measurement. SD\< 50% decrease in sum of the product of diameters of up to 6 target measurable nodes \& extranodal sites, no criteria for disease progression are met. Progressive disease requires one of the following:An individual node must be abnormal with: LDi 1.5cm \& Increase by 50% from PPD nadir \& an increase in LDi or SDi from nadir 0.5cm for lesions 2cm,1cm for lesions 2cm. In case of splenomegaly, the splenic length must increase by \>=50% of the extent of its prior increase beyond baseline.

  Time frame for response assessment was from Baseline to end of treatment or progression of disease up to 1 year.

Secondary Outcomes (1)

• Number of Participants With Adverse Events

  Baseline to end of treatment or progression of disease

Other Outcomes (1)

• Exploratory Objective to Define Change of mTOR Pathway Protein Phosphorylation and the Incidence of Activating Mutations in MTOR and Related Genes.

  Baseline to end of treatment or progression of disease

Study Arms (3)

Aggressive Non-Hodgkin Lymphoma (NHL) - TAK228

EXPERIMENTAL

Phase II - Aggressive NHL: Diffuse Large B Cell Lymphoma (DLBCL), Mantle Cell Lymphoma (MCL), Transformed Large Cell Lymphoma, and Follicular Lymphoma (FL) grade 3b Group Participants take TAK-228 1 time every day of a 28 day cycle. Treatment continues until progression of disease occurs, or a maximum of 12 months of treatment. Participant checks blood sugar every day before TAK-228 dose.

Drug: TAK228; Other: Blood Sugar Testing

Indolent Non-Hodgkin Lymphoma (NHL) - TAK228

EXPERIMENTAL

Phase II - Indolent NHL: Follicular Lymphoma (FL) grade 1-3a, Small Lymphocytic Lymphoma (SLL), Marginal Zone Lymphoma (MZL) Group Participants take TAK-228 1 time every day of a 28 day cycle. Treatment continues until progression of disease occurs, or a maximum of 12 months of treatment. Participant checks blood sugar every day before TAK-228 dose.

Drug: TAK228; Other: Blood Sugar Testing

Hodgkin Lymphoma - TAK228

EXPERIMENTAL

Phase II - Hodgkin Lymphoma Group Participants take TAK-228 1 time every day of a 28 day cycle. Treatment continues until progression of disease occurs, or a maximum of 12 months of treatment. Participant checks blood sugar every day before TAK-228 dose.

Drug: TAK228; Other: Blood Sugar Testing

Interventions

TAK228 DRUG

Starting dose of TAK228: 3 mg by mouth every day of a 28 day cycle.

Also known as: MLN0128

Aggressive Non-Hodgkin Lymphoma (NHL) - TAK228; Hodgkin Lymphoma - TAK228; Indolent Non-Hodgkin Lymphoma (NHL) - TAK228

Blood Sugar Testing OTHER

Participant given a glucometer to check pre-dose blood sugar levels at home every day.

Aggressive Non-Hodgkin Lymphoma (NHL) - TAK228; Hodgkin Lymphoma - TAK228; Indolent Non-Hodgkin Lymphoma (NHL) - TAK228

Eligibility Criteria

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

You may qualify if:

• Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
• Female patients who: are postmenopausal for at least 1 year before the screening visit, OR are surgically sterile, OR if they are of childbearing potential, agree to practice 1 effective methods of contraception and one additional effective (barrier) method, at the same time, from the time of signing the informed consent through 90 days (or longer, as mandated bu local labeling \[eg,USPI, SmPC, etc;\]) after the last dose of study drug, or agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient (Periodic abstinence \[e.g, calendar, ovulation, symptothermal, postovulation methods\] and withdrawal,spermicides only, ad lactational amenorrhea are not acceptable methods of contraception.Female and male condoms should not be used together.
• Male patients, even if surgically sterilized (ie, status post-vasectomy), who: agree to practice highly effective barrier contraception during the entire study treatment period and through 120 days after the last dose of study drug, or agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient (Periodic abstinence \[e.g, calendar, ovulation, symptothermal, postovulation methods for the female partner\] and withdrawal, spermicides only, ad lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together; Agree not to donate sperm during the course of this study or 120 days after receiving their last dose of study drug
• Patients must have a diagnosis of prior treated diffuse large b-cell lymphoma, mantle cell lymphoma, transformed lymphoma, follicular lymphoma (any grade), small lymphocytic lymphoma, marginal zone lymphoma, or Hodgkin lymphoma with at least 2 lines of therapy without a curative treatment options.
• Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status \</= 2.
• Adequate organ function, as specified below, within 3 weeks before the first dose of study drug: a) Bone marrow reserve consistent with: absolute neutrophil count (ANC) \>/=1.5 x 10\^9/L; platelet count \>/=100 x 10\^9/L; hemoglobin \>/=9 g/dL without transfusion within 1 week preceding study drug administration; b) Hepatic: total bilirubin \< /=1.5 x upper limit of normal (ULN), transaminases (aspartate aminotransferase-AST and alanine aminotransferase ALT) \</= 2.5 x ULN (\</= 5 x ULN if liver metastases are present); c) Renal: creatinine clearance \>/= 50 mL/min based either on Cockcroft-Gault estimate or based on urine collection (12 or 24 hour); d) Metabolic: fasting serum glucose (\</=130 mg/dL) and fasting triglycerides \</=300 mg/dL;
• Ability to swallow oral medications;
• Measurable disease, defined as \>/=1.5 cm on imaging assessment.

You may not qualify if:

• Eligible for therapy for the lymphoid malignancy which has a high likelihood of a curative result in the opinion of the investigator.
• Female patients who are both lactating and breastfeeding or have a positive serum pregnancy test during the screening period
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
• Concurrent malignancies except basal or squamous cell carcinoma of the skin, or cervical carcinoma in situ treated with curative intent. Any cancer from which the patient has been disease free for at least 2 years is permissible.
• Treatment with any investigational products within 14 days before the first dose of study drug
• Failed to recover to baseline or stable grade 1 from the reversible effects of prior anticancer therapies with the exception of alopecia.
• Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of TAK228; such as significant chronic diarrhea. In addition, patients with enteric stomata are also excluded.
• History of any of the following within the last 6 months prior to study entry: ischemic myocardial event, including angina requiring therapy and artery revascularization procedures; Ischemic cerebrovascular event, including TIA and artery revascularization procedures; Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia); Placement of a pacemaker for control of rhythm; New York Heart Association (NYHA) Class III or IV heart failure; Pulmonary embolism.
• History of any of the following within the last 6 months prior to study entry: Requirement of inotropic support; Serious uncontrolled cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia); Placement of a pacemaker for control of rhythm
• Significant active cardiovascular or pulmonary disease at the time of study entry, including: uncontrolled high blood pressure (i.e., systolic blood pressure \>180 mm Hg, diastolic blood pressure \> 95 mm Hg) Use of anti-hypertensive agents to control hypertension before cycle 1 day 1 is allowed; Pulmonary hypertension; Uncontrolled asthma or O2 saturation \< 90% by ABG (Arterial Blood Gas) analysis or pulse oximetry on room air; Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement; medically significant (symptomatic) bradycardia; History of arrhythmia requiring an implantable cardiac defibrillator; Baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTc interval \> 480 milliseconds, or history of congenital long QT syndrome, or torsades de pointes).
• Treatment with strong inhibitors and/or inducers of cytochrome P450 (CYP) 3A4, CYP2C9 or CYP2C19 within 1 week preceding the first dose of study drug.
• Patients receiving systemic corticosteroids (either IV or oral steroids, excluding inhalers or low-dose hormone replacement therapy as defined no greater than 20mg of prednisone daily) within 1 week before administration of the first dose of study drug.
• Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise participation of the patient in the study.
• Central nervous system (CNS) lymphoma.
• Known human immunodeficiency virus infection.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Takeda: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Lymphoma

Interventions

sapanisertib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Dr. Jason R. Westin/Lymphoma/Myeloma
• Organization: UT MD Anderson Cancer Center

jwestin@mdanderson.org

713-792-3750

Study Officials

• Jason R. Westin, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2016
• First Posted: April 5, 2016
• Study Start: March 1, 2017
• Primary Completion: July 10, 2018
• Study Completion: July 10, 2018
• Last Updated: March 12, 2020
• Results First Posted: March 12, 2020

Record last verified: 2020-03

Locations

US (1)