MOR00208 + Lenalidomide for Chronic Lymphocytic Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ohio State University Comprehensive Cancer Center

Must not be taking: CD19 antibodies, Alemtuzumab

Disqualifiers: Richter's transformation, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 12

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of combining two treatments, MOR00208 (an experimental treatment) and lenalidomide, for individuals with certain blood cancers, including chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or prolymphocytic leukemia (PLL). The treatments aim to halt cancer growth and enhance the immune system's ability to combat cancer cells. Another part of the trial examines the combination of MOR00208 with ibrutinib to assess their joint effectiveness. This trial may suit those with CLL, SLL, or PLL that is untreated or has recurred, especially if experiencing symptoms like severe fatigue or significant weight loss. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop any CLL treatments at least 4 weeks before starting the study, but you can continue taking palliative steroids at a low dose. The protocol does not specify other medication restrictions, so it's best to discuss your current medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of MOR00208 and lenalidomide is generally safe. Early studies indicate that patients tolerate this combination well. Some side effects occurred, but they were mostly manageable and typical for this type of treatment.

For the combination of MOR00208 and ibrutinib, studies suggest it is also safe. Ibrutinib alone effectively treats chronic lymphocytic leukemia and is known for its safety across various health conditions. When combined with MOR00208, the safety remains good, and early evidence shows this combination effectively targets cancer cells.

Overall, studies have shown that both treatment combinations are generally safe, with expected but manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for chronic lymphocytic leukemia (CLL) because they introduce innovative mechanisms that differ from standard treatments like chemotherapy, targeted therapy, and immunotherapy. MOR00208 is an anti-CD19 monoclonal antibody, which means it specifically targets CD19 proteins on the surface of cancer cells, potentially leading to more precise and effective eradication of cancerous cells. When combined with lenalidomide, known for modifying the immune system, or with ibrutinib, which blocks signals that tell cancer cells to grow, these combinations could enhance immune responses and improve patient outcomes more effectively than current options. This dual approach not only targets cancer cells directly but also boosts the body's natural defenses, offering a promising new avenue for treating CLL.

What evidence suggests that this trial's treatments could be effective for chronic lymphocytic leukemia?

This trial will evaluate the effectiveness of different treatment combinations for chronic lymphocytic leukemia (CLL). Research has shown that combining MOR00208 with lenalidomide may help treat CLL. MOR00208, a monoclonal antibody, targets cancer cells by identifying those with a marker called CD19, either stopping their growth or aiding the immune system in destroying them. Lenalidomide enhances immune function, which can also inhibit cancer cell growth. Together, these two drugs have shown early success in slowing cancer cell growth in people with CLL.

Another arm of this trial will test MOR00208 with ibrutinib. Ibrutinib disrupts the processes that support cancer cell growth and survival. Research suggests that using MOR00208 with ibrutinib might enhance the immune system's ability to fight CLL, making this combination another potential treatment option. ^{1 2 5 6 7}

Who Is on the Research Team?

Jennifer Woyach, MD

Principal Investigator

The Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with chronic lymphocytic leukemia, small lymphocytic lymphoma, or prolymphocytic leukemia that's come back or hasn't been treated. They should have symptoms like weight loss, fatigue, fever without infection, large spleen or lymph nodes. They need to be in good enough health to take pills and not have other serious illnesses or cancers that would interfere with the study.

Inclusion Criteria

Patients must be able to receive outpatient treatment and follow-up at the treating institution

Patients with a diagnosis of intermediate or high risk CLL, SLL, or B cell (B)-PLL by Biennial International Workshop on CLL (IWCLL) 2008 criteria who have

COHORT 1: previously untreated disease AND refuse or are ineligible for approved chemo- and/or -immunotherapy options for untreated CLL/SLL/PLL

Exclusion Criteria

Previous treatment with a CD19 antibody; prior lenalidomide is acceptable for patients on cohort 2

Patients who have received alemtuzumab within the previous 6 months

Patients with active Richter's transformation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive anti-CD19 monoclonal antibody MOR00208 and lenalidomide. Treatment repeats every 28 days for up to 12 courses.

12 months

Monthly visits for 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Lenalidomide
• MOR00208

Trial Overview Researchers are testing a combination of MOR00208 (an antibody targeting cancer cells) and lenalidomide (a drug that may boost the immune system) to see if they work better together against certain blood cancers. The trial will look at how well patients respond to this treatment combo.

How Is the Trial Designed?

Group I: Cohorts 1-3Treatment (MOR00208, lenalidomide) Experimental Treatment 3 Interventions

Patients receive anti-CD19 monoclonal antibody MOR00208 IV over 2 hours on day 1 (days 1, 2, 8, 15, and 22 of course 1 only) and lenalidomide PO daily on days 1-28 (days 9-28 of course 1 only). Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Correlative studies will be collected for this trial and will focus on the effects of MOR00208 alone and in combination with lenalidomide on immune effector cell number and function.

Group II: Cohort 4 Treatment (MOR00208, ibrutinib) Experimental Treatment 2 Interventions

Patients receive anti-CD19 monoclonal antibody MOR00208 IV over 2 hours on day 1 (days 1, 2, 8, 15, and 22 of course 1 only) and ibrutinib PO daily on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Correlative studies will be collected for this trial and will focus on the effects of MOR00208 alone and in combination with ibrutinib on immune effector cell number and function.

Lenalidomide is already approved in European Union, United States for the following indications:

Approved in European Union as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Approved in United States as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Who Is Running the Clinical Trial?

Ohio State University Comprehensive Cancer Center

Lead Sponsor

Trials

350

Recruited

295,000+

MorphoSys AG

Industry Sponsor

Trials

27

Recruited

6,600+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02639910

NCT02639910 | Study to Evaluate Safety and Preliminary ... This is a two-cohort, multicenter, open-label study of tafasitamab (MOR208) combined with idelalisib or venetoclax in adult patients with R/R CLL or R/R SLL ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4256907/

A phase 1 trial of the Fc-engineered CD19 antibody ... A phase 1 trial of the Fc-engineered CD19 antibody XmAb5574 (MOR00208) demonstrates safety and preliminary efficacy in relapsed CLL · Key Points. XmAb5574 is an ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6488229/

Pharmacotherapy of relapsed/refractory chronic ... As a single agent, it was relatively well tolerated and effective in RR CLL with an ORR of 67%[40]. It is being investigated in combination with lenalidomide, ...

4. tandfonline.com tandfonline.com/doi/full/10.1080/10428194.2021.1964020

Tafasitamab combined with idelalisib or venetoclax in ... Outcomes of patients with chronic lymphocytic leukemia after discontinuing ibrutinib. Source: Blood. Venetoclax–rituximab holds substantial promise in CLL.

5. researchgate.net researchgate.net/publication/336378499_Final_Results_and_Follow-up_of_a_Phase_I_Study_of_the_Fc_Engineered_CD19_Antibody_XmAbR5574_aka_MOR00208_in_Patients_with_Relapsed_or_Refractory_Chronic_Lymphocytic_Leukemia_CLL_or_Small_Lymphocytic_L

Final Results and Follow-up of a Phase I Study of the Fc ... We have previously presented safety and efficacy data from a first in human trial of this ab in relapsed or refractory (R/R) CLL, and now update ...

6. researchgate.net researchgate.net/publication/336417564_Updated_Results_from_a_Phase_II_Study_of_the_Fc_Engineered_CD19_Antibody_MOR208_in_Combination_with_Lenalidomide_for_Patients_with_Chronic_Lymphocytic_Leukemia_CLL_and_Richter's_Transformation_or_Ibru

Updated Results from a Phase II Study of the Fc ... MOR208 appears safe in combination with ibrutinib, and preliminary evidence of activity against CLL cells with BTK C481S has been observed.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40413564/

Real-World Safety Profile of Ibrutinib in Chronic ... Ibrutinib remains an effective treatment for lymphocytic leukemia, even in patients with comorbidities and high-risk genetic characteristics.