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

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)

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).

Study Overview

• Status: Completed
• Conditions: Diffuse Large B-cell Lymphoma
• Intervention / Treatment: Drug: Lenalidomide; Drug: Tafasitamab

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.

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium, 2020
    • ZNA Middelheim dep Klinische studies Hematologie
  • Kortrijk, Belgium, 8500
    • AZ Groeninge-Campus Maria's Voorzienigheid
  • Liege, Belgium, 4000
    • Centre Hospitalier Universitaire (Chu) de Liege
  • Yvoir, Belgium, 5530
    • Clinique Universitaire de Mont Godinne
• Czechia
  • Olomouc, Czechia, 779 00
    • University Hospital Olomouc Hematoonkologicka klinika
• France
  • Clermont-Ferrand, France, 63000
    • CHU De Clermont Ferrand - Hopital Estaing Service Hematologie Clinique Et Thrapie Cellulaire
  • Limoges, France, 87042
    • Centre Hospitalier Universitaire (CHU) De Limoges Hopital Dupuytren
  • Lyon, France, 69495
    • Centre Hospitalier Lyon-Sud (CHLS)
  • Paris, France, 75015
    • Hopital Universitaire Necker Enfants Malades Service de Hematologie Adultes
• Germany
  • Essen, Germany, 45147
    • Universitatsklinikum Essen, Abteilung Haematologie
  • Frankfurt, Germany, 60488
    • Krankenhaus Nordwest GmbH - Institut Fuer Klinisch-Onkologische Forschung (IKF)
  • Munich, Germany, 81337
    • Klinikum Grosshadern-Klinikum Der Ludwig-Maximilian Universitaet Muenchen
  • Nürnberg, Germany, 90419
    • Klinikum Nuernberg Nord Medizinische Klinik 5 Hamatologie
  • Würzburg, Germany, 97080
    • Universitaetsklinikum Wuerzburg
• Hungary
  • Budapest, Hungary, 1038
    • Semmelweis Egyetem I. Sz. Belgyogyaszati Klinika-Semmelweis University
  • Budapest, Hungary, 1122
    • National Institute of Oncology Hematological Department
  • Debrecen, Hungary, 4032
    • DEKK, Belgyogyaszati Klinika
  • Kaposvár, Hungary, 7400
    • Somogy Megyei Kaposi Mor Oktato Korhaz (Kaposi Mor County Hospital)
• Italy
  • Bari, Italy, 70124
    • Azienda Ospedaliera Univerisitaria Policlinico Consorziale Di Bari UOC Ematologia con Trapianto
  • Bologna, Italy, 40138
    • Ist.Ematologia E Oncologia Medica L.E A.Seragnoli Azienda Ospedaliero-Universitaria, Policlinico S.Orsola-Malpighi
  • Firenze, Italy, 50134
    • Azienda Ospedaliero Universitaria Careggi-S.O.D. Patologia Medica
  • Modena, Italy, 41124
    • Azienda Ospedaliero - Universitaria Policlinico di Modena Dip di Medicina Diagnostica, Clinica e di Sanità Pubblica
  • Novara, Italy, 28100
    • AOU Maggiore della Cartia
  • Perugia, Italy, 6132
    • A .O. S. Maria della Misericordia
  • Roma, Italy, 00133
    • Tor Vergata University Department Of Hematology
  • Terni, Italy, 5100
    • Az Ospedaliera Santa Maria Facolta di Medicina e Chirurgia
  • Torino, Italy, 10126
    • A.O.U. Città della Salute e della Scienza di Torino
• Poland
  • Krakow, Poland, 30-510
    • Pratia MCM Krakow
  • Olsztyn, Poland, 10228
    • Samodzielny Publiczny Zaklad Opieki Zdrowotnej MSWiA z Warmimsko
  • Opole, Poland, 45061
    • Szpital Wojewodzk I w Opolu SP ZOZ Oddzial Hematologii i Onkologii Hematologicznej
  • Poznan, Poland, 60631
    • Samodzielny Publiczny Zaklad Opieki Zdrowotnej Ministerstwa Spraw Wewnetrznych w Poznaniu im. prof. Ludwika Bierkowskiego
  • Rzeszow, Poland, 35055
    • Szpital Wojewodzki Nr 1 im. Fryderyka Chopina w Rzeszowie
  • Warsaw, Poland, 02781
    • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
  • Warszawa, Poland, 02106
    • MTZ Clinical Research Sp. z o.o
  • Warszawa, Poland, 02781
    • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy Klinika Nowotworow Ukladu Chlonnego Ul.
• Spain
  • Badalona, Spain, 08916
    • Hospital Universitari Germans Trias i Pujol (HUGTP)
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08097
    • Institut Catala D'Oncologia-Hospital Duran Y Reynals
  • Madrid, Spain, 28222
    • Hospital Universitario Puerta de Hierro de Majadahonda
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz Servicio de Hematologia Unidad de Linformas Oncohealth Institute
  • Pamplona, Spain, 31008
    • Complejo Hospitalario de Navarra (CHN)
  • Pozuelo De Alarcón, Spain, 28223
    • Hospital Universitario Quiron Salud Madrid
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio, Hospital de la Mujer Servicio de Hematologia
• United Kingdom
  • Bournemouth, United Kingdom, BH77DW
    • The Royal Bournemouth & Christchurch Hospitals
  • Liverpool, United Kingdom, L7 8XP
    • Royal Liverpool University Hospital - Liverpool University Hospitals NHS Foundation Trust
  • London, United Kingdom, W1G 6AD
    • Sarah Cannon Research Institute
  • Newcastle, United Kingdom, NE7 7DN
    • The Newcastle Hospitals NHS Foundation Trust
• United States
  • California
    • Bakersfield, California, United States, 93309
      • CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center
    • Los Angeles, California, United States, 90095
      • UCLA - David Geffen School of Medicine
    • Redondo Beach, California, United States, 90277
      • Cancer Care - Torrance Memorial Physician Network
    • Santa Maria, California, United States, 93454
      • Central Coast Medical Oncology Corporation
  • Colorado
    • Grand Junction, Colorado, United States, 81501
      • St. Mary's Hospital And Regional Medical Center
  • Connecticut
    • Norwalk, Connecticut, United States, 06856
      • Norwalk Hospital
  • Michigan
    • Ypsilanti, Michigan, United States, 48179
      • St. Joseph Mercy Hospital Cancer Care Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Charleston Hematology Oncology Associates
  • Texas
    • Tyler, Texas, United States, 75701
      • Tyler Hematology-Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: Lenalidomide; 25 mg; Other Names: Revlimid®; LEN; Drug: Tafasitamab; 12 mg/kg; Other Names: MOR00208

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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
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
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
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.
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
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

Collaborators and Investigators

• Sponsor: MorphoSys AG
• Investigators: Principal Investigator: Johannes Duell, MD, MorphoSys AG

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2016
• Primary Completion (Actual): November 14, 2022
• Study Completion (Actual): April 19, 2023

Study Registration Dates

• First Submitted: March 13, 2015
• First Submitted That Met QC Criteria: March 25, 2015
• First Posted (Estimated): March 26, 2015

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: September 28, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: lenalidomide; DLBCL; Efficacy; MOR00208; Tafasitamab
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide
• Other Study ID Numbers: MOR208C203; 2014-004688-19 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes