Open Label Study to Evaluate the Safety and Efficacy of Lenalidomide With MOR00208 in Patients With R-R DLBCL

Diffuse Large B-cell Lymphoma Clinical Trial

— L-MIND  

Official title:

A Phase II, Single-Arm, Open-Label, Multicentre Study to Evaluate the Safety and Efficacy of Lenalidomide Combined With MOR00208 in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R-R DLBCL)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02399085
• Other study ID #: MOR208C203
• Secondary ID: 2014-004688-19
• Status: Completed
• Phase: Phase 2
• Start date: March 29, 2016
• Est. completion date: April 19, 2023

Study information

• Verified date: September 2023
• Source: MorphoSys AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase II, Single-Arm, Open-Label, Multicentre Study to Evaluate the Safety and Efficacy of Lenalidomide Combined with MOR00208 in Participants with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (R-R DLBCL).

Description:

The aim of this single-arm, multicentre, open-label Phase II study is to evaluate the Lenalidomide (LEN) combined with Tafasitamab (MOR00208) in adult participants with DLBCL who had relapsed after or were refractory to at least one, but no more than three previous systemic regimens administered for the treatment of their DLBCL and who were not candidates for high-dose chemotherapy and subsequent Autologous stem cell transplants and were thus considered to have exhausted their therapeutic options. One prior therapy line had to include an anti-CD20 targeted therapy (e.g., rituximab [RTX]).

MOR00208 and LEN were administered for up to 12 cycles (28 days each), followed by MOR00208 monotherapy until progression, in participants with at least stable disease or a better response.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 81
• Est. completion date: April 19, 2023
• Est. primary completion date: November 14, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Major Inclusion Criteria:

1. Age >18 years

2. Histologically confirmed diagnosis of DLBCL

3. Tumour tissue for central pathology review and correlative studies had to be provided.

4. Participants must had:

• relapsed and/or refractory disease

• at least one bidimensionally measurable, PET positive disease site (transverse diameter of =1.5 cm and perpendicular diameter of =1.0 cm at baseline)

• received at least one, but no more than three previous systemic regimens for the treatment of DLBCL and one therapy line must had included a CD20-targeted therapy

• Eastern Cooperative Oncology Group 0 to 2

5. Participants were not considered in the opinion of the investigator eligible, or participants unwilling to undergo intensive salvage therapy including ASCT

6. Participants had to meet the following laboratory criteria at screening:

• absolute neutrophil count =1.5 × 10^9/L

• platelet count =90 × 10^9/L

• total serum bilirubin =2.5 × ULN or =5 × ULN in cases of Glibert's Syndrome or liver involvement by lymphoma

• alanine transaminase, aspartate aminotransferase and alkaline phosphatase =3 × ULN or <5 × ULN in cases of liver involvement

• serum creatinine clearance =60 mL/minute

7. Females of childbearing potential (FCBP) must:

• not be pregnant

• refrain from breastfeeding and donating blood or oocytes

• agreed to ongoing pregnancy testing

• committed to continued abstinence from heterosexual intercourse, or agree to use and be able to comply with the use of double-barrier contraception

8. Males (if sexually active with a FCBP) had to

• use an effective barrier method of contraception

• refrain from donating blood or sperm

9. In the opinion of the investigator the participants had to:

• be able and willing to receive adequate prophylaxis and/or therapy for thromboembolic events

• be able to understand, give written informed consent and comply with all study-related procedures, medication use, and evaluations

• had no history of noncompliance in relation to medical regimens or not be considered potentially unreliable and/or uncooperative

• be able to understand the reason for complying with the special conditions of the pregnancy prevention risk management plan and gave written acknowledgement of this.

Major Exclusion Criteria:

1. Participants who had:

• other histological type of lymphoma

• primary refractory DLBCL

• a history of "double/triple hit" genetics

2. Participants who had, within 14 days prior to Day 1 dosing:

• not discontinued CD20-targeted therapy, chemotherapy, radiotherapy, investigational anticancer therapy or other lymphoma specific therapy

• underwent major surgery or suffered from significant traumatic injury

• received live vaccines.

• required parenteral antimicrobial therapy for active, intercurrent infections

3. Participants who:

• had, in the opinion of the investigator, not recovered sufficiently from the adverse toxic effects of prior therapies

• were previously treated with CD19-targeted therapy or immunomodulatory drugs (IMiDs)® (e.g., thalidomide, LEN)

• had a history of hypersensitivity to compounds of similar biological or chemical composition to MOR00208, IMiDs® and/or the excipients contained in the study drug formulations

• had undergone ASCT within the period = 3 months prior to the signing of the Informed Consent Form. Patients who had a more distant history of ASCT had to exhibit full haematological recovery before enrolment into the study

• had undergone previous allogenic stem cell transplantation

• had a history of deep venous thrombosis/embolism, threatening thromboembolism or known thrombophilia or were at a high risk for a thromboembolic event in the opinion of the investigator and who were not willing/able to take venous thromboembolic event prophylaxis during the entire treatment period

• concurrently used other anti-cancer or experimental treatments

4. Prior history of malignancies other than DLBCL, unless the participant had been free of the disease for =5 years prior to screening.

5. Participants with:

• positive hepatitis B and/or C serology.

• known seropositivity for or history of active viral infection with human immunodeficiency virus (HIV)

• CNS lymphoma involvement

• history or evidence of clinically significant cardiovascular, CNS and/or other systemic disease that would in the investigator's opinion preclude participation in the study or compromised the participant's ability to give informed consent.

Related Conditions & MeSH terms

• Diffuse Large B-cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Tafasitamab
12 mg/kg
• Lenalidomide
25 mg

Locations

Country	Name	City	State
Belgium	ZNA Middelheim dep Klinische studies Hematologie	Antwerp
Belgium	AZ Groeninge-Campus Maria's Voorzienigheid	Kortrijk
Belgium	Centre Hospitalier Universitaire (CHU) de Liege	Liege
Belgium	Clinique Universitaire de Mont Godinne	Yvoir
Czechia	University Hospital Olomouc Hematoonkologicka klinika	Olomouc
France	CHU De Clermont Ferrand - Hopital Estaing Service Hematologie Clinique Et Thrapie Cellulaire	Clermont-Ferrand
France	Centre Hospitalier Universitaire (CHU) De Limoges Hopital Dupuytren	Limoges
France	Centre Hospitalier Lyon-Sud (CHLS)	Lyon
France	Hopital Universitaire Necker Enfants Malades Service de Hematologie Adultes	Paris
Germany	Universitatsklinikum Essen, Abteilung Haematologie	Essen
Germany	Krankenhaus Nordwest GmbH - Institut Fuer Klinisch-Onkologische Forschung (IKF)	Frankfurt
Germany	Klinikum Grosshadern-Klinikum Der Ludwig-Maximilian Universitaet Muenchen	Munich
Germany	Klinikum Nuernberg Nord Medizinische Klinik 5 Hamatologie	Nürnberg
Germany	Universitaetsklinikum Wuerzburg	Würzburg
Hungary	National Institute of Oncology Hematological Department	Budapest
Hungary	Semmelweis Egyetem I. Sz. Belgyogyaszati Klinika-Semmelweis University	Budapest
Hungary	DEKK, Belgyogyaszati Klinika	Debrecen
Hungary	Somogy Megyei Kaposi Mor Oktato Korhaz (Kaposi Mor County Hospital)	Kaposvár
Italy	Azienda Ospedaliera Univerisitaria Policlinico Consorziale Di Bari UOC Ematologia con Trapianto	Bari
Italy	Ist.Ematologia E Oncologia Medica L.E A.Seragnoli Azienda Ospedaliero-Universitaria, Policlinico S.Orsola-Malpighi	Bologna
Italy	Azienda Ospedaliero Universitaria Careggi-S.O.D. Patologia Medica	Firenze
Italy	Azienda Ospedaliero - Universitaria Policlinico di Modena Dip di Medicina Diagnostica, Clinica e di Sanità Pubblica	Modena
Italy	AOU Maggiore della Cartia	Novara
Italy	A .O. S. Maria della Misericordia	Perugia
Italy	Tor Vergata University Department Of Hematology	Roma
Italy	Az Ospedaliera Santa Maria Facolta di Medicina e Chirurgia	Terni
Italy	A.O.U. Citta della Salute e della Scienza di Torino	Torino
Poland	Pratia MCM Krakow	Krakow
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej MSWiA z Warmimsko	Olsztyn
Poland	Szpital Wojewodzk I w Opolu SP ZOZ Oddzial Hematologii i Onkologii Hematologicznej	Opole
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej Ministerstwa Spraw Wewnetrznych w Poznaniu im. prof. Ludwika Bierkowskiego	Poznan
Poland	Szpital Wojewodzki Nr 1 im. Fryderyka Chopina w Rzeszowie	Rzeszow
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy	Warsaw
Poland	MTZ Clinical Research Sp. z o.o	Warszawa
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy Klinika Nowotworow Ukladu Chlonnego Ul.	Warszawa
Spain	Hospital Universitari Germans Trias i Pujol (HUGTP)	Badalona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Institut Catala D'Oncologia-Hospital Duran Y Reynals	Barcelona
Spain	Hospital Universitario Fundacion Jimenez Diaz Servicio de Hematologia Unidad de Linformas Oncohealth Institute	Madrid
Spain	Hospital Universitario Puerta de Hierro de Majadahonda	Madrid
Spain	Complejo Hospitalario de Navarra (CHN)	Pamplona
Spain	Hospital Universitario Quiron Salud Madrid	Pozuelo De Alarcón
Spain	Hospital Universitario Virgen del Rocio, Hospital de la Mujer Servicio de Hematologia	Sevilla
United Kingdom	The Royal Bournemouth & Christchurch Hospitals	Bournemouth
United Kingdom	Royal Liverpool University Hospital - Liverpool University Hospitals NHS Foundation Trust	Liverpool
United Kingdom	Sarah Cannon Research Institute	London
United Kingdom	The Newcastle Hospitals NHS Foundation Trust	Newcastle
United States	CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center	Bakersfield	California
United States	Charleston Hematology Oncology Associates	Charleston	South Carolina
United States	Ohio State University Medical Center	Columbus	Ohio
United States	St. Mary's Hospital And Regional Medical Center	Grand Junction	Colorado
United States	UCLA - David Geffen School of Medicine	Los Angeles	California
United States	Norwalk Hospital	Norwalk	Connecticut
United States	Cancer Care - Torrance Memorial Physician Network	Redondo Beach	California
United States	Central Coast Medical Oncology Corporation	Santa Maria	California
United States	Tyler Hematology-Oncology	Tyler	Texas
United States	St. Joseph Mercy Hospital Cancer Care Center	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
MorphoSys AG

Countries where clinical trial is conducted

United States,  Belgium,  Czechia,  France,  Germany,  Hungary,  Italy,  Poland,  Spain,  United Kingdom, 

References & Publications (3)

Duell J, Maddocks KJ, Gonzalez-Barca E, Jurczak W, Liberati AM, De Vos S, Nagy Z, Obr A, Gaidano G, Abrisqueta P, Kalakonda N, Andre M, Dreyling M, Menne T, Tournilhac O, Augustin M, Rosenwald A, Dirnberger-Hertweck M, Weirather J, Ambarkhane S, Salles G. — View Citation

Duell J, Obr A, Augustin M, Endell J, Liu H, Geiger S, Silverman IM, Ambarkhane S, Rosenwald A. CD19 expression is maintained in DLBCL patients after treatment with tafasitamab plus lenalidomide in the L-MIND study. Leuk Lymphoma. 2022 Feb;63(2):468-472. — View Citation

Salles G, Duell J, Gonzalez Barca E, Tournilhac O, Jurczak W, Liberati AM, Nagy Z, Obr A, Gaidano G, Andre M, Kalakonda N, Dreyling M, Weirather J, Dirnberger-Hertweck M, Ambarkhane S, Fingerle-Rowson G, Maddocks K. Tafasitamab plus lenalidomide in relaps — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Best Objective Response Rate (ORR)	ORR = complete response [CR] + partial response [PR]; Independent Radiology/Clinical Review Committee (IRC) Evaluation.; ORR after MOR00208 and Lenalidomide combination therapy assessed by the IRC evaluation.; ORR was defined as the number of participants of the total number of participants treated with MOR00208 + LEN with CR or PR as best response achieved at any time during the study.	Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled
Secondary	Duration of Response (DoR) by IRC Evaluation	DoR [months] = (date of assessment of tumor progression or death - date of assessment of first documented response of (CR or PR) + 1)/30.4375.	Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled
Secondary	DoR by Investigator (INV) Evaluation	DoR [months] = (date of assessment of tumour progression or death - date of assessment of first documented response of (CR or PR) + 1)/30.4375.	Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled
Secondary	Progression-free Survival (PFS) by IRC Evaluation	PFS time was defined as the time (in months) from the date of the first administration of any study drug to the date of tumor progression or death from any cause.	Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled
Secondary	PFS by INV Evaluation	PFS time was defined as the time (in months) from the date of the first administration of any study drug to the date of tumor progression or death from any cause.	Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled
Secondary	Overall Survival (OS)	OS was defined as the time from the date of the first administration of any study drug until death from any cause (documented by the date of death).	Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled
Secondary	Disease Control Rate (DCR) by IRC Evaluation	DCR = CR + PR + SD (Stable disease); IRC Evaluation DCR was defined as the number of participants having CR, PR or SD based on the best objective response achieved at any time during the study.	Approximately 2.5 years after first participant enrolled
Secondary	DCR by INV Evaluation	DCR = CR + PR + SD (Stable disease); IRC Evaluation DCR was defined as the number of participants having CR, PR or SD based on the best objective response achieved at any time during the study.	Approximately 2.5 years after first participant enrolled
Secondary	Time to Progression (TTP) by IRC Evaluation	TTP is defined as the time from the first administration of any study drug until documented DLBCL progression or death as a result of lymphoma.	Approximately 2.5 years after first participant enrolled
Secondary	TTP by INV Evaluation	TTP is defined as the time from the first administration of any study drug until documented DLBCL progression or death as a result of lymphoma.	Approximately 2.5 years after first participant enrolled
Secondary	Time to Next Treatment (TTNT)	Kaplan-Meier analysis of TTNT in FAS population. TTNT is defined as the time from the first administration of any study drug to the institution of next anti-neoplastic therapy (for any reason including disease progression, treatment toxicity and participant preference) or death of any cause, whatever comes first.	Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled
Secondary	Event-free Survival (EFS) by IRC Evaluation	EFS is defined as the time (in months) from the date of the first administration of any study drug to the date of tumour progression, first initiation of a new non-study anti-neoplastic therapy or death from any cause whichever comes first.	Approximately 4.5 years after first participant enrolled; Approximately 6.5 years after first participant enrolled
Secondary	Serum Drug Levels of MOR00208	The pharmacokinetics (PK) profile of MOR00208 was investigated by quantifying serum drug levels at baseline and after repeated IV administrations for up to 24 treatment cycles using sparse sampling.; MOR00208 PK sample was taken pre-dose and 1 hour ± 10 min after the end of MOR00208 infusion for Cycle 1 to Cycle 23. MOR00208 PK sample (pre-dose only) were taken in odd numbered additional treatment cycles only (e.g., treatment Cycles 13, 15,17, 19, 21, 23).	Cycle 1 Days 1, 4, 15 predose and 1 hr post-dose; Cycle 2 Days 1, 15 predose and 1 hr post-dose; Cycle 3 Days 1, 15 predose and 1 hr post-dose; Cycles 4, 5, 6, 7, 9, 11,13, 15, 17, 19, 21, 23 Day 1 predose; End of Treatment
Secondary	Number of Participants Who Developed Anti-MOR00208 Antibodies	The Anti-MOR00208 Antibodies were investigated by quantifying serum drug levels at baseline and after repeated intravenous (IV) administrations planned for up to 24 treatment cycles using sparse sampling. Anti-MOR00208 antibody sample (pre-dose only) were taken in odd numbered additional treatment cycles only (e.g., treatment Cycles 13, 15,17, 19, 21,23).	Baseline, Up to a maximum of 23 cycles.
Secondary	Number of Participants That Experienced Treatment-emergent Adverse Events (TEAEs)	TEAEs are defined as any adverse event reported in the following time interval (including the lower and upper limits): date of first administration of study treatment; date of last administration of study treatment + 30 days, or if they are considered to be related to the study drug.	Approximately 6.5 years after first participant enrolled
Secondary	Severity of Treatment-emergent Adverse Events (TEAEs)	Number of participants with Severity of TEAEs during MOR00208 and LEN combination therapy.	Approximately 6.5 years after first participant enrolled

External Links

•   CD19 expression is maintained in DLBCL patients after treatment with tafasitamab plus lenalidomide in the L-MIND study
•   Long-term outcomes from the Phase II L-MIND study of tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma
•   Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study