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
• Last Update Posted: June 6, 2019
• Sponsor: MorphoSys AG
• Information provided by (Responsible Party): MorphoSys AG

Tracking Information

• First Submitted Date: March 13, 2015
• First Posted Date: March 26, 2015
• Last Update Posted Date: June 6, 2019
• Study Start Date: March 2016
• Actual Primary Completion Date: November 2018 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: December 5, 2017): Objective response rate (ORR = complete response [CR] + partial response [PR]) [ Time Frame: 1-3 years approximately ]
• Original Primary Outcome Measures (submitted: March 25, 2015): Objective response rate (ORR = complete response [CR] + partial response [PR]) [ Time Frame: 3 years ]
• Change History: Complete list of historical versions of study NCT02399085 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: December 5, 2017)

• Disease control rate (DCR) [ Time Frame: 1-3 years approximately ]
  DCR = CR + PR + SD
• Duration of response (DoR) [ Time Frame: 1-3 years approximately ]
• Progression-free survival (PFS) [ Time Frame: 1-3 years approximately ]
• Overall survival (OS) [ Time Frame: 1-3 years approximately ]
• Safety of LEN combined with MOR00208 according to the frequency and severity of adverse events (AEs) [ Time Frame: 1-3 years approximately ]
  Safety profile is assessed according to the frequency and severity of adverse events (AEs)
• Potential immunogenicity of MOR00208 [ Time Frame: upto 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: upto 2 years ]
  time to maximum serum concentration [tmax]

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: 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 weeks cycles, until disease progression or unacceptable toxicity or discontinuation due to any other reason.

Lenalidomide (Revlimid®), PO, daily, 4 weeks 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 *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated 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: June 2019