What side effects are associated with this type of intervention?

The most common treatments for Central Nervous System (CNS) Lymphoma, particularly those involving immunomodulatory drugs like Lenalidomide and anti-CD19 monoclonal antibodies like Tafasitamab, are associated with several side effects. Lenalidomide can cause neutropenia, thrombocytopenia, anemia, fatigue, and an increased risk of infections. Tafasitamab may lead to infusion-related reactions, neutropenia, anemia, and respiratory infections. When combined, these treatments could potentially amplify these side effects, requiring careful monitoring and supportive care.

What prior FDA approvals exist?

The FDA has approved several treatments for CNS Lymphoma, though specific approvals for combinations like Lenalidomide and Tafasitamab are still under investigation. Lenalidomide, an immunomodulatory drug, has shown efficacy in various hematologic malignancies, including CNS lymphomas. Tafasitamab, an anti-CD19 monoclonal antibody, is being studied for its potential to enhance blood-brain barrier permeability and improve treatment outcomes in CNS lymphoma. While these specific combinations are not yet FDA-approved, they represent a promising area of research in the treatment of relapsed CNS lymphoma.

What other types of research exist?

Promising novel alternatives for CNS Lymphoma treatment in 2024 include: 1) Chimeric Antigen Receptor (CAR) T cell therapies targeting CD19, such as Lisocabtagene Maraleucel and Axicabtagene Ciloleucel, which have shown efficacy in relapsed/refractory lymphomas. 2) Bispecific T cell engagers (BiTEs) like Blinatumomab, which targets CD19 and has demonstrated activity in B-cell malignancies. 3) PD-1/PD-L1 inhibitors such as Pembrolizumab and Nivolumab, which are being explored for their potential in various lymphomas, including those with CNS involvement.

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Immunomodulatory imide drugs (IMiDs)

Tafasitamab + Lenalidomide for CNS Lymphoma

Phase 1 & 2

Recruiting

Led By James Rubenstein, MD, PhD

Research Sponsored by James Rubenstein

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Individuals with a history of hepatitis C virus (HCV) infection must have been treated and cured. For individuals with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.

Participants must have histologically or cytologically confirmed relapsed primary or secondary B-cell CNS lymphoma, DLBCL type (recurrence documented by flow-cytometry is also acceptable).

Must not have

Prior receipt of anti-CD19 based therapy including anti-CD19, Chimeric antigen receptor T cells (CAR-T) therapy is an exclusion criteria.

Has received systemic anti-cancer therapies within 2 weeks of first dose, radiation within 1 week, antibody therapy within 4 weeks.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of lenalidomide and Tafasitamab in patients with brain cancer that has returned after previous treatments. Lenalidomide, a derivative of thalidomide, is known to boost the immune system and directly target cancer cells, potentially improving drug delivery to the brain.

Who is the study for?

Adults with relapsed B-cell CNS lymphoma, including those who've had stem cell transplants but not recent anti-cancer treatments or certain other therapies. Must have good organ function and no serious medical issues that could affect safety. Women of childbearing age must agree to pregnancy testing and use contraception.

What is being tested?

The trial is exploring the effectiveness of Tafasitamab combined with Lenalidomide in patients with relapsed CNS lymphoma. It's an open-label study, meaning everyone knows what treatment they're getting, focusing on how well this combination crosses the blood-brain barrier.

What are the potential side effects?

Potential side effects include reactions related to the immune system, such as infusion reactions from Tafasitamab and birth defects if taken during pregnancy due to Lenalidomide. Other risks may involve changes in blood counts and liver function.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I had hepatitis C but am cured, or I'm being treated with no detectable virus.

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My B-cell CNS lymphoma has returned, confirmed by tests.

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My hepatitis B virus load is undetectable with treatment.

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My blood counts and liver/kidney functions are within normal ranges.

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My cancer has spread to my brain, spinal cord, and eyes.

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I have had treatment specifically for lymphoma in my brain.

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I am mostly active and can care for myself.

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I am 18 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have never received anti-CD19 or CAR-T therapy.

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I haven't had cancer treatments like chemotherapy, radiation, or antibody therapy in the specified time before starting this trial.

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I have a lymphoma in my brain after a transplant.

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I am not pregnant or breastfeeding, and if of child-bearing potential, I am using effective birth control.

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I have a history of HIV infection.

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I have recovered from previous cancer treatment side effects, except for hair loss.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum Tolerated Dose (MTD) (Phase 1)

Percentage of participants with demonstrated Clinical Benefit Rate (CBR) (Phase 2)

Proportion of participants with dose limiting toxicities (DLTs) (Phase 1)

+1 more

Secondary study objectives

Median Overall Survival (OS)

Median Progression-free survival (PFS) (Phase 2)

Proportion of participants with Treatment-Related Adverse Events

Side effects data

From 2023 Phase 2 trial • 81 Patients • NCT02399085

64%

Any TEAE

49%

Neutropenia

37%

Diarrhoea

37%

Anaemia

30%

Cough

28%

Thrombocytopenia

26%

Asthenia

25%

Oedema peripheral

22%

Pyrexia

22%

Decreased appetite

20%

Back pain

19%

Hypokalaemia

19%

Constipation

16%

Fatigue

15%

Vomiting

15%

Bronchitis

15%

Muscle spasms

15%

Nausea

12%

Leukopenia

12%

Urinary tract infection

12%

Dyspnoea

11%

Respiratory tract infection

11%

C-reactive protein increased

10%

Abdominal pain

10%

Nasopharyngitis

10%

Upper respiratory tract infection

10%

Pruritus

10%

Rash

10%

Pain in extremity

10%

Hypomagnesaemia

Pneumonia

Rhinitis

Headache

Paraesthesia

Blood creatinine increased

Hypertension

Sinusitis

Abdominal pain upper

Mucosal inflammation

Gastroenteritis

Gamma-glutamyltransferase increased

Anxiety

Oropharyngeal pain

Arthralgia

Hypotension

Sciatica

Rash maculo-papular

Febrile neutropenia

Dysuria

Blood alkaline phosphatase increased

Hyperglycaemia

Productive cough

Lymphopenia

Hypocalcaemia

Hypogammaglobulinaemia

Infusion related reaction

COVID-19

Pulmonary embolism

Basal cell carcinoma

Lower respiratory tract infection

Squamous cell carcinoma

Atrial fibrillation

Cardiac failure congestive

Enterobacter bacteraemia

Intervertebral discitis

Bowen's disease

Lung adenocarcinoma

Cholecystitis

Klebsiella sepsis

Influenza

Febrile infection

Escherichia bacteraemia

Transient ischaemic attack

Cardio-respiratory arrest

Haematoma

Prostate cancer

Myelodysplastic syndrome

Breast cancer

Bronchopulmonary aspergillosis

Cerebrovascular accident

Cervicobrachial syndrome

Transient global amnesia

Sudden death

COVID-19 pneumonia

Gastroenteritis rotavirus

Myeloproliferative neoplasm

Cytomegalovirus infection

Neutropenic sepsis

Parainfluenzae virus infection

Progressive multifocal leukoencephalopathy

Respiratory syncytial virus infection

Sepsis

Soft tissue infection

Streptococcal sepsis

Urinary tract infection enterococcal

Varicella zoster virus infection

Lower limb fracture

Wound complication

Tumour flare

Biliary colic

Muscular weakness

Agranulocytosis

Cardiac failure

Myocardial ischaemia

Cognitive disorder

Facial paralysis

Chronic obstructive pulmonary disease

Respiratory failure

Arthritis

Osteonecrosis

Pathological fracture

Femur fracture

Renal failure

Deep vein thrombosis

100%

80%

60%

40%

20%

Study treatment Arm

Treatment (MOR00208, Lenalidomide)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Phase 2 (Tafasitamab, Lenalidomide)Experimental Treatment2 Interventions

Participants will be given 12mg of Tafasitamab on days 1, 4, 8, 15, and 22 of cycle 1, days 1, 8, 15, and 22 of cycles 2 \& 3, and days 1 and 15 for any cycle thereafter. Participants will also be given daily Lenalidomide on days 1-21 of each cycle at the recommended phase 2 dose.

Group II: Phase 1 (Tafasitamab, Lenalidomide)Experimental Treatment2 Interventions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Tafasitamab

2016

Completed Phase 3

~630

Lenalidomide

2005

Completed Phase 3

~2240

0 / 14Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Lenalidomide and tafasitamab are promising treatments for Central Nervous System (CNS) Lymphoma due to their complementary mechanisms of action. Lenalidomide enhances the immune response by boosting T-cell and natural killer (NK) cell activity, while also inhibiting angiogenesis and cytokine release. Tafasitamab, an anti-CD19 monoclonal antibody, targets the CD19 antigen on B-cells, leading to cell death through antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis. This combination is particularly significant for CNS Lymphoma patients as it may improve the immune system's ability to penetrate the blood-brain barrier and effectively target lymphoma cells within the CNS.

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.