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

NCT ID: NCT02399085

Last Updated: 2023-10-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 81 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-29
• Study Completion Date: 2023-04-19

Brief 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).

Detailed 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.

Conditions

Diffuse Large B-cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tafasitamab (MOR00208) + lenalidomide (LEN)

MOR00208:

MOR00208 was administered via IV infusion at a dose of 12 mg/kg. For the first three cycles (Cycles 1 to 3) of the study each cycle consisted of a MOR00208 infusion on Day 1, Day 8, Day 15 and Day 22 of the cycle.

Additionally, a loading dose was administered on Day 4 of Cycle 1. Thereafter MOR00208 was administered on a bi-weekly (every 14 days) basis with infusions on Day 1 and Day 15 of each 28-day cycle.

LEN:

Participants self-administered a starting dose of 25 mg oral LEN daily on Days 1-21 of each cycle, for up to 12 cycles in total. LEN dose could be modified in a de-escalating fashion or discontinued based upon clinical and laboratory findings.

On days when both study drugs were given together, LEN was administered prior to MOR00208.

Group Type: EXPERIMENTAL

Tafasitamab

Intervention Type: DRUG

12 mg/kg

Lenalidomide

Intervention Type: DRUG

25 mg

Interventions

Tafasitamab

12 mg/kg

Intervention Type: DRUG

Lenalidomide

25 mg

Intervention Type: DRUG

Other Intervention Names

MOR00208; LEN; Revlimid®

Eligibility Criteria

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.

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.

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

Sponsors

MorphoSys AG

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Johannes Duell, MD

Role: PRINCIPAL_INVESTIGATOR

MorphoSys AG

Locations

CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center

Bakersfield, California, United States

UCLA - David Geffen School of Medicine

Los Angeles, California, United States

Cancer Care - Torrance Memorial Physician Network

Redondo Beach, California, United States

Central Coast Medical Oncology Corporation

Santa Maria, California, United States

St. Mary's Hospital And Regional Medical Center

Grand Junction, Colorado, United States

Norwalk Hospital

Norwalk, Connecticut, United States

St. Joseph Mercy Hospital Cancer Care Center

Ypsilanti, Michigan, United States

Ohio State University Medical Center

Columbus, Ohio, United States

Charleston Hematology Oncology Associates

Charleston, South Carolina, United States

Tyler Hematology-Oncology

Tyler, Texas, United States

ZNA Middelheim dep Klinische studies Hematologie

Antwerp, , Belgium

AZ Groeninge-Campus Maria's Voorzienigheid

Kortrijk, , Belgium

Centre Hospitalier Universitaire (CHU) de Liege

Liège, , Belgium

Clinique Universitaire de Mont Godinne

Yvoir, , Belgium

University Hospital Olomouc Hematoonkologicka klinika

Olomouc, , Czechia

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, , France

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

Nuremberg, , Germany

Universitaetsklinikum Wuerzburg

Würzburg, , Germany

Semmelweis Egyetem I. Sz. Belgyogyaszati Klinika-Semmelweis University

Budapest, , Hungary

National Institute of Oncology Hematological Department

Budapest, , Hungary

DEKK, Belgyogyaszati Klinika

Debrecen, , Hungary

Somogy Megyei Kaposi Mor Oktato Korhaz (Kaposi Mor County Hospital)

Kaposvár, , Hungary

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

Florence, , 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, , Italy

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

Rzeszów, , Poland

MTZ Clinical Research Sp. z o.o

Warsaw, , Poland

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy Klinika Nowotworow Ukladu Chlonnego Ul.

Warsaw, , Poland

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy

Warsaw, , Poland

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

Seville, , Spain

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 Kingdom

Countries

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

References

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 relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol. 2020 Jul;21(7):978-988. doi: 10.1016/S1470-2045(20)30225-4. Epub 2020 Jun 5.

Reference Type: RESULT

PMID: 32511983 (View on PubMed)

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. 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. Haematologica. 2021 Sep 1;106(9):2417-2426. doi: 10.3324/haematol.2020.275958.

Reference Type: RESULT

PMID: 34196165 (View on PubMed)

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. doi: 10.1080/10428194.2021.1986219. Epub 2021 Nov 15. No abstract available.

Reference Type: RESULT

PMID: 34779360 (View on PubMed)

Duell J, Abrisqueta P, Andre M, Gaidano G, Gonzales-Barca E, Jurczak W, Kalakonda N, Liberati AM, Maddocks KJ, Menne T, Nagy Z, Tournilhac O, Kuffer C, Bakuli A, Amin A, Gurbanov K, Salles G. Tafasitamab for patients with relapsed or refractory diffuse large B-cell lymphoma: final 5-year efficacy and safety findings in the phase II L-MIND study. Haematologica. 2024 Feb 1;109(2):553-566. doi: 10.3324/haematol.2023.283480.

Reference Type: DERIVED

PMID: 37646664 (View on PubMed)

Cherng HJ, Westin JR. Broadening the MIND: Tafasitamab and Lenalidomide versus Synthetic Controls. Clin Cancer Res. 2022 Sep 15;28(18):3908-3910. doi: 10.1158/1078-0432.CCR-22-1626.

Reference Type: DERIVED

PMID: 35861632 (View on PubMed)

Nowakowski GS, Yoon DH, Peters A, Mondello P, Joffe E, Fleury I, Greil R, Ku M, Marks R, Kim K, Zinzani PL, Trotman J, Huang D, Waltl EE, Winderlich M, Kurukulasuriya NC, Ambarkhane S, Hess G, Salles G. Improved Efficacy of Tafasitamab plus Lenalidomide versus Systemic Therapies for Relapsed/Refractory DLBCL: RE-MIND2, an Observational Retrospective Matched Cohort Study. Clin Cancer Res. 2022 Sep 15;28(18):4003-4017. doi: 10.1158/1078-0432.CCR-21-3648.

Reference Type: DERIVED

PMID: 35674661 (View on PubMed)

Zinzani PL, Rodgers T, Marino D, Frezzato M, Barbui AM, Castellino C, Meli E, Fowler NH, Salles G, Feinberg B, Kurukulasuriya NC, Tillmanns S, Parche S, Dey D, Fingerle-Rowson G, Ambarkhane S, Winderlich M, Nowakowski GS. RE-MIND: Comparing Tafasitamab + Lenalidomide (L-MIND) with a Real-world Lenalidomide Monotherapy Cohort in Relapsed or Refractory Diffuse Large B-cell Lymphoma. Clin Cancer Res. 2021 Nov 15;27(22):6124-6134. doi: 10.1158/1078-0432.CCR-21-1471. Epub 2021 Aug 25.

Reference Type: DERIVED

PMID: 34433649 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://pubmed.ncbi.nlm.nih.gov/34779360/

CD19 expression is maintained in DLBCL patients after treatment with tafasitamab plus lenalidomide in the L-MIND study

https://pubmed.ncbi.nlm.nih.gov/32511983/

Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study

https://pubmed.ncbi.nlm.nih.gov/34196165/

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

Other Identifiers

2014-004688-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MOR208C203

Identifier Type: -

Identifier Source: org_study_id