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

Refractory Follicular Lymphoma Clinical Trial

— LOTIS-6  

Official title:

A Phase 2 Randomized Study of Loncastuximab Tesirine Versus Idelalisib in Patients With Relapsed or Refractory Follicular Lymphoma (LOTIS-6)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04699461
• Other study ID #: ADCT 402-202
• Secondary ID: 2020-003695-40
• Status: Terminated
• Phase: Phase 2
• Start date: November 4, 2021
• Est. completion date: November 25, 2022

Study information

• Verified date: September 2023
• Source: ADC Therapeutics S.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: November 25, 2022
• Est. primary completion date: November 25, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Follicular
• Refractory Follicular Lymphoma
• Relapsed Follicular Lymphoma

Intervention

Drug:
• Loncastuximab Tesirine
IV infusion
• Idelalisib
Oral tablet

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Centre Hospitalier Universitaire Universite Catholique de Louvain	Yvoir
France	Centre Hospitalier de Dunkerque	Dunkerque
France	Centre Hospitalier de La Rochelle	La Rochelle
France	Centre de Lutte Contre le Cancer - Centre Henri-Becquerel	Rouen
France	Hôpital Bretonneau	Tours Cedex 9
Hungary	Országos Onkológiai Intézet	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Pécsi Tudományegyetem Klinikai Központ	Pécs
Israel	Soroka Medical Center	Be'er Sheva
Israel	Carmel Medical Center	Haifa
Israel	Rabin Medical Center - Beilinson Hospital	Petah tikva
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Israel	The Chaim Sheba Medical Center	Tel Aviv
Italy	Azienda Ospedaliero - Universitaria Careggi	Firenze
Poland	Szpitale Pomorskie Spólka Z Ograniczona Odpowiedzialnoscia	Gdynia
Poland	Pratia Onkologia Katowice	Katowice
Poland	Pratia Poznan	Skorzewo
Spain	Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)	L'Hospitalet De Llobregat
Spain	Hospital Universitari Arnau de Vilanova	Lleida
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario Fundación Jiménez Díaz	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Universitario Quirónsalud Madrid	Pozuelo De Alarcón
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Switzerland	Inselspital Universitätsspital Bern	Bern
United Kingdom	NHS Greater Glasgow and Clyde	Glasgow
United Kingdom	Account University College London Hospitals NHS Foundation Trust	London
United States	Hollings Cancer Center	Charleston	South Carolina
United States	Summit Medical Group	Florham Park	New Jersey
United States	Summit Medical Group - Florham Park Campus	Florham Park	New Jersey
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada

Sponsors (1)

Lead Sponsor	Collaborator
ADC Therapeutics S.A.

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Response Rate (CRR)	CRR was defined as the percentage of participants who experienced a best overall response (BOR) of complete response (CR) assessed prior to any subsequent anticancer treatment.	Up to the end of treatment, maximum time on treatment was 333 days
Secondary	Overall Response Rate (ORR)	ORR was defined as the percentage of participants with a BOR of CR or partial response (PR) assessed prior to any subsequent anticancer treatment.	Up to end of treatment, maximum time on treatment was 333 days
Secondary	Progression-Free Survival (PFS)	PFS was defined as the time between the randomization date and the first documentation of recurrence, progression, or death.	Up to end of treatment, maximum time on treatment was 333 days
Secondary	Overall Survival (OS)	OS was defined as the time between the randomization date and death from any cause.	Up to end of treatment, maximum time on treatment was 333 days
Secondary	Duration of Response (DOR)	DOR was defined as the time from the documentation of tumor response to disease progression or death.	Up to end of treatment, maximum time on treatment was 333 days
Secondary	Number of Participants Who Experienced at Least One Treatment-Emergent Adverse Event (TEAE)	TEAEs were defined as an AE that occurs or worsens in the period extending from the first dose of study treatment until 30 days after the last dose of study treatment or start of new anti-cancer therapy, whichever is earlier.; Any clinically significant changes from baseline in the safety laboratory values, vital signs, 12-lead electrocardiogram (ECG), and Eastern Cooperative Oncology Group (ECOG) performance status were reported as TEAEs.	Day 1 to 30 days after end of treatment, maximum time on treatment was 333 days
Secondary	Average Concentration of Loncastuximab Tesirine Before Infusion		Up to end of treatment, maximum time on treatment was 333 days
Secondary	Average Concentration of Loncastuximab Tesirine at the End of Infusion		Up to end of treatment, maximum time on treatment was 333 days
Secondary	Clearance Rate of Loncastuximab Tesirine		Up to end of treatment, maximum time on treatment was 333 days
Secondary	Volume of Distribution of Loncastuximab Tesirine		Up to end of treatment, maximum time on treatment was 333 days
Secondary	Number of Participants With Anti-Drug Antibody (ADA) Titers to Loncastuximab Tesirine		Up to end of treatment, maximum time on treatment was 333 days
Secondary	Change From Baseline in Health-Related Quality of Life (HRQoL) as Measured by the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L)		Up to end of treatment, maximum time on treatment was 333 days
Secondary	Change From Baseline in Health-Related Quality of Life (HRQoL) as Measured by the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym)		Up to end of treatment, maximum time on treatment was 333 days
Secondary	Number of Participants With Specific Symptomatic Adverse Event Symptoms As Selected From Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)	The specific symptomatic adverse events includes fatigue, swelling, rash, nausea, diarrhea, abdominal pain, and cough.	Up to end of treatment, maximum time on treatment was 333 days
Secondary	Treatment-Related Symptoms as Assessed by Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)	The specific symptoms assessed include fatigue, swelling, rash, nausea, diarrhea, abdominal pain, and cough. The severity is assessed from "None" to "Very severe" and the interference level is assessed from "Not at all" to "Very much."	Up to end of treatment, maximum time on treatment was 333 days