Study to Evaluate the Efficacy and Safety of Loncastuximab Tesirine Versus Idelalisib in Participants With Relapsed or Refractory Follicular Lymphoma

NCT ID: NCT04699461

Last Updated: 2023-10-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-04
• Study Completion Date: 2022-11-25

Brief Summary

This study aims to evaluate the efficacy of single agent loncastuximab tesirine compared to idelalisib in participants with relapsed or refractory follicular lymphoma.

Conditions

Relapsed Follicular Lymphoma; Refractory Follicular Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Loncastuximab Tesirine

Participants will be administered loncastuximab tesirine as an intravenous (IV) infusion on Day 1 of each cycle, where 1 cycle is 3 weeks. Loncastuximab tesirine will be administered at a dose of 150 μg/kg for 2 cycles, then at a dose of 75 μg/kg for subsequent cycles.

Group Type: EXPERIMENTAL

Loncastuximab Tesirine

Intervention Type: DRUG

IV infusion

Idelalisib

Participants will be administered 150 mg idelalisib, orally, twice a day throughout each cycle, where 1 cycle is 4 weeks.

Group Type: ACTIVE_COMPARATOR

Idelalisib

Intervention Type: DRUG

Oral tablet

Interventions

Loncastuximab Tesirine

IV infusion

Intervention Type: DRUG

Idelalisib

Oral tablet

Intervention Type: DRUG

Other Intervention Names

Zynlonta; ADCT-402

Eligibility Criteria

Inclusion Criteria

• Written informed consent must be obtained prior to any study procedures.
• Male or female participants aged 18 years or older, with pathologic diagnosis of follicular lymphoma (FL) (Grade 1, 2, 3A) in the most recent tumor biopsy.
• Relapsed or refractory disease following two or more treatment regimens, at least one of which must have contained an anti-CD20 therapy.
• Participants who have received previous CD19-directed therapy must have a biopsy which shows CD19 expression after completion of the CD19-directed therapy.
• Measurable disease as defined by the 2014 Lugano Classification as assessed by positron emission tomography - computed tomography (PET-CT) or, if not Fluorodeoxyglucose (FDG) avid, CT or magnetic resonance imaging (MRI).
• Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block (or minimum 10 freshly cut unstained slides if block is not available). Note: Any biopsy since initial diagnosis is acceptable, but if several samples are available, the most recent sample is preferred.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
• Adequate organ function as defined by screening laboratory values within the following parameters:

1. Absolute neutrophil count (ANC) ≥1.0 × 10^3/μL (off growth factors at least 72 hours),

2. Platelet count ≥75 × 10^3/μL without transfusion in the past 2 weeks,

3. Alanine aminotransferase, AST, and GGT ≤2.5 × the upper limit of normal (ULN),

4. Total bilirubin ≤1.5 × ULN (participants with known Gilbert's syndrome may have a total bilirubin up to ≤3 × ULN),

5. Calculated creatinine clearance ≥30 mL/min by the Cockcroft and Gault equation. Note: A laboratory assessment may be repeated a maximum of two times during the Screening period to confirm eligibility

• Women of childbearing potential (WOCBP)(1) must agree to use a highly effective method(2) of contraception from the time of giving informed consent until at least 9 months after the last dose of study treatment. Men with female partners who are of childbearing potential must agree to use a condom when sexually active or practice total abstinence from the time of giving informed consent until at least 6 months after the participant receives his last dose of study treatment.

1. WOCBP are defined as sexually mature women who have not undergone bilateral tubal ligation, bilateral oophorectomy, or hysterectomy; or who have not been postmenopausal. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.

2. Highly effective forms of birth control are methods that achieve a failure rate of less than 1% per year when used consistently and correctly. Highly effective forms of birth control include hormonal contraceptives associated with inhibition of ovulation (oral, injectable, patch, intrauterine devices), male partner sterilization, or total abstinence from heterosexual intercourse, when this is the preferred and usual lifestyle of the participant.

Note: The double-barrier method (e.g., synthetic condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel), periodic abstinence (such as calendar, symptothermal, post ovulation), withdrawal (coitus interruptus), lactational amenorrhea method, and spermicide-only are not acceptable as highly effective methods of contraception.

Exclusion Criteria

• Previous treatment with loncastuximab tesirine.
• Previous treatment with idelalisib.
• History of hypersensitivity to any of the excipients of loncastuximab tesirine or idelalisib.
• Follicular lymphoma which has transformed to diffuse large B-cell lymphoma (DLBCL) or other aggressive lymphomas.
• Requires treatment or prophylaxis with a strong cytochrome P450 (CYP) 3A inhibitor, inducer, or sensitive substrate.
• History of or ongoing drug-induced pneumonitis.
• History of or ongoing inflammatory bowel disease.
• Any condition that could interfere with the absorption or metabolism of idelalisib including malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel.
• Active second primary malignancy other than non-melanoma skin cancers, nonmetastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy that the Sponsor's medical monitor and Investigator agree and document should not be exclusionary.
• Autologous transplant within 30 days prior to start of study treatment (C1D1).
• Allogenic transplant within 60 days prior to start of study treatment (C1D1).
• Active graft-versus-host disease.
• Post-transplantation lymphoproliferative disorders.
• Human immunodeficiency virus (HIV) seropositive with any of the following:

1. CD4+ T-cell counts <350 cells/μL.

2. Acquired immuno-deficiency syndrome (AIDS)-defining opportunistic infection within 12 months prior to screening.

3. Not on anti-retroviral therapy, or on anti-retroviral therapy for < 4 weeks at the time of screening.

4. HIV viral load ≥400 copies/mL.

• Serologic evidence of chronic hepatitis B infection and unable or unwilling to receive standard prophylactic anti-viral therapy or with detectable hepatitis B virus (HBV) viral load.
• Serologic evidence of hepatitis C infection without completion of curative treatment or with detectable hepatitis C virus (HCV) viral load.
• History of Stevens-Johnson syndrome or toxic epidermal necrolysis.
• Lymphoma with active central nervous system involvement, including leptomeningeal disease.
• Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath).
• Breastfeeding or pregnant.
• Significant medical comorbidities, including but not limited to, uncontrolled hypertension (BP ≥160/100 mm Hg repeatedly), unstable angina, congestive heart failure (greater than New York Heart Association class II), electrocardiographic evidence of acute ischemia, coronary angioplasty or myocardial infarction within 6 months prior to screening, uncontrolled atrial or ventricular cardiac arrhythmia, poorly controlled diabetes, or severe chronic pulmonary disease.
• Any Grade ≥3 active infection which requires IV antibiotics, IV antiviral, or IV antifungal treatment.
• Major surgery, radiotherapy, chemotherapy or other anti-neoplastic therapy within 14 days prior to start of study treatment (C1D1), except shorter if approved by the Sponsor.
• Use of any other experimental medication within 30 days prior to start of study treatment (C1D1).
• Live vaccine administration within 4 weeks prior to Cycle(C) 1 Day (D) 1.
• Failure to recover to ≤ Grade 1 (Common Terminology Criteria for Adverse Events [CTCAE] version 5.0) from acute non-hematologic toxicity (except ≤Grade 2 neuropathy or alopecia) due to previous therapy prior to screening.
• Any other significant medical illness, abnormality, or condition that would, in the Investigator's judgment, make the participant inappropriate for study participation or put the participant at risk.

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

Sponsors

ADC Therapeutics S.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Comprehensive Cancer Centers of Nevada - Central Valley

Las Vegas, Nevada, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Summit Medical Group - Florham Park Campus

Florham Park, New Jersey, United States

Summit Medical Group

Florham Park, New Jersey, United States

Hollings Cancer Center

Charleston, South Carolina, United States

Universitair Ziekenhuis Gent

Ghent, , Belgium

Centre Hospitalier Universitaire Universite Catholique de Louvain

Yvoir, , Belgium

Centre Hospitalier de Dunkerque

Dunkirk, , France

Centre Hospitalier de La Rochelle

La Rochelle, , France

Centre de Lutte Contre le Cancer - Centre Henri-Becquerel

Rouen, , France

Hôpital Bretonneau

Tours, , France

Semmelweis Egyetem

Budapest, , Hungary

Országos Onkológiai Intézet

Budapest, , Hungary

Pécsi Tudományegyetem Klinikai Központ

Pécs, , Hungary

Soroka Medical Center

Beersheba, , Israel

Carmel Medical Center

Haifa, , Israel

Rabin Medical Center - Beilinson Hospital

Petah Tikva, , Israel

The Chaim Sheba Medical Center

Tel Aviv, , Israel

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Azienda Ospedaliero - Universitaria Careggi

Florence, , Italy

Szpitale Pomorskie Spółka Z Ograniczoną Odpowiedzialnością

Gdynia, , Poland

Pratia Onkologia Katowice

Katowice, , Poland

Pratia Poznań

Skorzewo, , Poland

Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)

L'Hospitalet de Llobregat, , Spain

Hospital Universitari Arnau de Vilanova

Lleida, , Spain

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

Hospital Universitario Fundación Jiménez Díaz

Madrid, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Universitario Quirónsalud Madrid

Pozuelo de Alarcón, , Spain

Hospital Universitario Virgen del Rocío

Seville, , Spain

Inselspital Universitätsspital Bern

Bern, , Switzerland

NHS Greater Glasgow and Clyde

Glasgow, , United Kingdom

Account University College London Hospitals NHS Foundation Trust

London, , United Kingdom

Countries

United States; Belgium; France; Hungary; Israel; Italy; Poland; Spain; Switzerland; United Kingdom

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2020-003695-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ADCT 402-202

Identifier Type: -

Identifier Source: org_study_id