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

• ClinicalTrials.gov Identifier: NCT02399085
• Recruitment Status: Active, not recruiting
• First Posted: March 26, 2015
• Results First Posted: February 5, 2020
• Last Update Posted: February 6, 2020
• Sponsor: MorphoSys AG
• Information provided by (Responsible Party): MorphoSys AG

Tracking Information

• First Submitted Date: March 13, 2015
• First Posted Date: March 26, 2015
• Results First Submitted Date: November 27, 2019
• Results First Posted Date: February 5, 2020
• Last Update Posted Date: February 6, 2020
• Study Start Date: March 2016
• Actual Primary Completion Date: November 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 23, 2020)

Number of Participants With Best Objective Response Rate [ Time Frame: 1-3 years approximately ]

ORR = complete response [CR] + partial response [PR]; IRC Evaluation

• Original Primary Outcome Measures (submitted: March 25, 2015): Objective response rate (ORR = complete response [CR] + partial response [PR]) [ Time Frame: 3 years ]

Current Secondary Outcome Measures (submitted: January 23, 2020)

• Disease Control Rate (DCR) [ Time Frame: 1-3 years approximately ]
  DCR = CR + PR + SD; IRC Evaluation
• Duration of Response (DoR) [ Time Frame: 1-3 years approximately ]
  IRC Evaluation
• Progression-free Survival (PFS) [ Time Frame: 1-3 years approximately ]
  IRC Evaluation
• Percentage of Participants With Overall Survival (OS) [ Time Frame: Approximately 32 months between first patient first visit and primary outcome completion date ]
  Overall survival was defined as first administration of IMP and deaths due to any cause. Percentage of patients alive at 12 months from the start of their study participation is reported.

Original Secondary Outcome Measures (submitted: March 25, 2015)

• Disease Control Rate (DCR) [ Time Frame: 3 years ]
  DCR = CR + PR + SD
• Duration of Response (DoR) [ Time Frame: 3 years ]
• Progression-free Survival (PFS) [ Time Frame: 3 years ]
• Overall survival (OS) [ Time Frame: 3 years ]
• Time to progression (TTP) [ Time Frame: 3 years ]
• Time to next treatment (TTNT) [ Time Frame: 3 years ]
  TTNT is defined as the time from study entry (= first dosing) to the institution of next therapy for any reason including disease progression, treatment toxicity and patient preference. TTNT will be descriptively analysed.
• Safety of LEN combined with MOR00208 according to the frequency and severity of adverse events (AEs) [ Time Frame: 2 years ]
  Safety profile is assessed according to the frequency and severity of adverse events (AEs)
• Potential immunogenicity of MOR00208 [ Time Frame: 2 years ]
  The absolute number and percentage of patients, who develop anti-MOR00208 antibodies, and the results of semi-quantitative anti-MOR00208 antibody titre determinations of confirmed positive sample assessments will be tabulated
• Pharmacokinetics (PK) of MOR00208 [ Time Frame: 2 years ]
  maximum serum concentration [Cmax]
• Pharmacokinetics (PK) of MOR00208 [ Time Frame: 2 years ]
  time to maximum serum concentration [tmax]
• Pharmacokinetics (PK) of MOR00208 [ Time Frame: 2 years ]
  apparent trough serum concentration before dosing [Cpd]
• Pharmacokinetics (PK) of MOR00208 [ Time Frame: 2 years ]
  area under the serum concentration versus time curve from time 0 to the time t of the last quantifiable concentration [AUC0-t]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Safety and Efficacy of Lenalidomide With MOR00208 in Patients With R-R DLBCL
• 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)
• Brief Summary: This is an open-label, multicentre study to characterize the safety and efficacy of the human anti CD19 antibody MOR00208 in combination with Lenalidomide in adult subjects with relapsed/refractory Diffuse Large B-cell Lymphoma (DLBCL) who have had at least one, but no more than three prior systemic regimens and who are not eligible for high dose chemotherapy (HDC) with autologous stem-cell transplantation (ASCT) at the time of study entry.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Diffuse Large B-cell Lymphoma

Intervention

• Drug: MOR00208
  12 mg/kg
  Other Name: MOR208
• Drug: Lenalidomide
  25 mg
  Other Names:

  • CC-5013
  • IMiD-1
  • Revlimid

Study Arms

Experimental: Treatment (MOR00208, lenalidomide)

MOR00208 Fc-Optimized Anti-CD19 Antibody, intravenous Infusion, weekly (Cycle 1-3) to bi-weekly (Cycle 4 onwards), 4 week cycles, until disease progression or unacceptable toxicity or discontinuation due to any other reason.

Lenalidomide (Revlimid®), PO, daily, 4 week cycles, lenalidomide is used 3 of the 4 weeks. Up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Interventions:

• Drug: MOR00208
• Drug: Lenalidomide

• Publications *: Salles G, Duell J, González Barca E, Tournilhac O, Jurczak W, Liberati AM, Nagy Z, Obr A, Gaidano G, André 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: December 5, 2017): 81
• Original Estimated Enrollment (submitted: March 25, 2015): 80
• Estimated Study Completion Date: November 2022
• Actual Primary Completion Date: November 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Major Inclusion Criteria:

1. Age >18 years
2. Histologically confirmed diagnosis of DLBCL
3. Tumour tissue for central pathology review and correlative studies must be provided.

4. Patients must have:

   • 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 have included a CD20-targeted therapy
   • Eastern Cooperative Oncology Group 0 to 2
5. Patients not considered in the opinion of the investigator eligible, or patients unwilling to undergo intensive salvage therapy including ASCT

6. Patients must meet the following laboratory criteria at screening:

   • absolute neutrophil count ≥1.5 × 109/L
   • platelet count ≥90 × 109/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
   • agree to ongoing pregnancy testing
   • commit 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) must

   • use an effective barrier method of contraception
   • refrain from donating blood or sperm

9. In the opinion of the investigator the patients must:

   • be able and willing to receive adequate prophylaxis and/or therapy for thromboembolic events
   • be able to understand the reason for complying with the special conditions of the pregnancy prevention risk management plan and give written acknowledgement of this.

Major Exclusion Criteria:

1. Patients who have:

   • other histological type of lymphoma
   • primary refractory DLBCL
   • a history of "double/triple hit" genetics

2. Patients who have, within 14 days prior to Day 1 dosing:

   • not discontinued CD20-targeted therapy, chemotherapy, radiotherapy, investigational anticancer therapy or other lymphoma specific therapy
   • undergone major surgery or suffered from significant traumatic injury
   • received live vaccines.
   • required parenteral antimicrobial therapy for active, intercurrent infections

3. Patients who:

   • were previously treated with CD19-targeted therapy or IMiDs® (e.g. thalidomide, LEN)
   • have undergone ASCT within the period ≤ 3 months prior to signing the informed consent form.
   • have undergone previous allogenic stem cell transplantation
   • have a history of deep venous thrombosis/embolism and who are not willing/able to take venous thromboembolic event prophylaxis during the entire treatment period
   • concurrently use other anticancer or experimental treatments
4. Prior history of malignancies other than DLBCL, unless the patient has been free of the disease for ≥5 years prior to screening.

5. Patients 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 compromise the patient's ability to give informed consent.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Czechia, France, Germany, Hungary, Italy, Poland, Spain, United Kingdom, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT02399085
• Other Study ID Numbers: MOR208C203
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: MorphoSys AG
• Study Sponsor: MorphoSys AG
• Collaborators: Not Provided

Investigators

• Study Director: Sumeet V Ambarkhane, MD; Clinical Program Leader

• PRS Account: MorphoSys AG
• Verification Date: January 2020