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CNS LymphomaPhase 1/2NCT05351593

Tafasitamab Plus Lenalidomide in Relapsed CNS Lymphoma

A Phase 1/2 study testing Tafasitamab and Lenalidomide in people with CNS Lymphoma and Primary Central Nervous System Lymphoma, run by James Rubenstein at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This is a single arm open-label multicenter phase I/II investigation of combination lenalidomide/Tafasitamab in patients with relapsed central nervous system (CNS) lymphoma. This is the first study to examine a naked anti-CD19 monoclonal antibody in relapsed CNS lymphoma patients as well as the combination of… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Tafasitamab and Lenalidomide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
1 siteUnited States
Study dates
8 Jun 2022to 30 Sep 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants must have relapsed primary or secondary CNS lymphoma, diffuse large B-cell lymphoma (DLBCL) type, based on radiographic, ophthalmologic, or CSF criteria (evidence of malignant cells based on CSF studies: cytospin/cytology and flow-cytometry).
  • Concomitant systemic lymphoma as well as transformation from follicular lymphoma and/or Chronic lymphocytic leukemia (CLL) to an aggressive B-cell histology is allowed.
  • Participants are eligible with disease in each CNS compartment: brain, leptomeninges/CSF and intraocular compartment.
  • Age >= 18 years.
  • Anticipated survival > 2 months, as determined by the investigator.
  • Eastern Cooperative Oncology Group (ECOG) performance status <=1 (Karnofsky performance status >= 70%)
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  • Demonstrates adequate organ function as defined below:
  • Absolute neutrophil count (ANC) ≥ 1.5 X 10^9/ L (1,500/ microliter (mcL), growth factors permitted).
  • Platelets >= 50 X 10^9 / L (50,000/ mcL, platelet transfusion independent).
  • Total bilirubin <= 1.5 x institutional upper limit of normal,unless elevated due to Gilbert's syndrome.
  • Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) <=3 X institutional upper limit of normal.
  • Alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) <=3 X institutional upper limit of normal.
  • Creatinine clearance (CrCl, calculated) >= 60 mL/min/1.73 m^2, calculated using the Cockcroft-Gault equation. CrCl > 60 mL/min/1.73 m2 is requisite for eligibility for the phase I dose-escalation phase of the study.
  • Ability to understand and the willingness to sign a written informed consent document.
  • For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. If a HBV test comes up positive due to Intravenous immunoglobulin (IVIG) and the participant has no prior history of HBV, then perform a HBV Polymerase chain reaction (PCR) to confirm undetectable disease.
  • 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.
  • Individuals with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
  • The effects of the study drugs on the developing human fetus are unknown. For this reason, and because the teratogenic effect of lenalidomide in humans cannot be ruled out, females of child-bearing potential (FCBP) and men must agree to use adequate contraception. FCBP must agree to undergo pregnancy testing as required in the study protocol. Should a woman become pregnant or suspect they are pregnant while their partner is participating in this study, they should inform her treating physician immediately.
  • Prior Therapies
  • Participants with CNS lymphoma involving the brain parenchyma must have received at least one prior systemic therapy.
  • Participants with secondary CNS lymphoma must have received prior CNS-directed treatment.
  • There is no limit in terms of prior lines of therapy received. Patients may have progressed after prior treatment with IMiD's (including lenalidomide, pomalidomide and CC122), patients may have had prior rituximab or other anti-CD20 based therapy as well as autologous and allogeneic stem cell transplant. Patients who progress after prior stem cell transplant are immediately eligible whereas patients that progress after anti-CD19-based therapy including CAR-T based therapy are not eligible.
  • Recipients of prior hematopoietic stem cell transplant are eligible as long as the following criteria are met:
  • Absence of graft versus host disease.
  • Discontinuation of systemic immunosuppressant therapy.

Who cannot join

  • Has received systemic anti-cancer therapies within 2 weeks of first dose, radiation within 1 week, antibody therapy within 4 weeks.
  • Has not recovered from adverse events due to prior anti-cancer therapy to ≤ grade 1 or baseline (other than alopecia).
  • Is currently receiving any other investigational agents.
  • Has participated in a study of an investigational product and received study treatment or used an investigational device within four weeks of the first dose of treatment.
  • Has a history of HIV infection.
  • Has CNS post-transplant lymphoproliferative disease (PTLD).
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  • Has known hypersensitivity to lenalidomide or Tafasitamab.
  • Pregnant women and women of child-bearing potential who will not using an effective method of birth control (detailed in Appendix 3) are excluded from this study because the study drugs have potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lenalidomide and/or Tafasitamab, breastfeeding should be discontinued if the mother is treated with study drugs.
  • Prior receipt of anti-CD19 based therapy including anti-CD19, Chimeric antigen receptor T cells (CAR-T) therapy is an exclusion criteria.
  • Has any significant medical condition or comorbidity that could compromise patient safety (e.g., uncontrolled serious infection).

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

UCSF Hematopoietic Malignancies Clinical Trial Recruitment contact

877-827-3222

HDFCCC.Heme@ucsf.edu

United States1 site, 1 recruiting

  • University of California, San Francisco

    San Francisco, California, 94143

    UCSF Hematopoietic Malignancies Clinical Trial Recruitment, 877-827-3222, HDFCCC.Heme@ucsf.edu

    cancertrials@ucsf.edu

    Recruiting

Other trials in United States

About this study

Official title: A Phase I/II Study of Tafasitamab Plus Lenalidomide in Relapsed CNS Lymphoma

This is a single arm open-label multicenter phase I/II investigation of combination lenalidomide/Tafasitamab in patients with relapsed central nervous system (CNS) lymphoma. This is the first study to examine a naked anti-CD19 monoclonal antibody in relapsed CNS lymphoma patients as well as the combination of anti-CD19 antibody plus an Immunomodulatory imide drugs (IMiDs) in CNS lymphomas. This study will also test the novel hypothesis that Tafasitamab enhances blood-brain barrier permeability, a potential property that could have broad clinical implications.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of lenalidomide in combination with Tafasitamab in patients with relapsed central nervous system (CNS) lymphoma (Phase 1).

II. To evaluate the clinical benefit rate of Tafasitamab in combination with lenalidomide in relapsed CNS lymphoma (Phase 2).

SECONDARY OBJECTIVES:

  1. To describe the toxicities of Tafasitamab in combination with lenalidomide in relapsed CNS lymphoma.

II. To describe the efficacy of Tafasitamab in combination with lenalidomide in relapsed CNS lymphoma.

EXPLORATORY OBJECTIVES:

  1. To obtain pilot information about cerebral spinal fluid (CSF) penetration of Tafasitamab as well as CSF partition coefficient of lenalidomide in combination with Tafasitamab to evaluate possibility that Tafasitamab enhances CSF penetration of lenalidomide to an extent greater than CSF/plasma partition coefficient of lenalidomide which was 20% at 15 and 20 milligram (mg) dose levels.

II. To evaluate the relationship between tumor mutational profile and response to Tafasitamab plus lenalidomide, via whole exome sequencing of diagnostic specimens.

II. To evaluate change in immune cell phenotypes in CSF and blood in patients via flow-cytometry of natural killer (NK) cell, T-cells and CSF monocytes/macrophages in patients treated with combination Tafasitamab plus lenalidomide.

IV. To evaluate the relationship between CSF cytokine microenvironment such as Interleukin-10 (IL-10), Chemokine ligand 13 (CXCL13), etc. as well as CSF metabolites, including energy metabolites and neurotransmitters, and response to combination Tafasitamab plus lenalidomide Tafasitamab, PFS, OS, and neurocognitive endpoints.

  1. To test the hypothesis that Tafasitamab in combination with lenalidomide impacts blood-brain barrier permeability associated with CNS lymphoma lesions, as assessed by albumin levels and MRI vascular permeability imaging metrics.

VI. To explore the correlation between immune cell subsets and response and/or resistance to lenalidomide/Tafasitamab.

VII. To evaluate the relationship between Minimal Residual Disease status (MRD) and response and PFS using either circulating tumor DNA or Clonoseq technologies.

STUDY DESIGN:

This is a single arm open-label multicenter phase I/II investigation of combination lenalidomide/Tafasitamab in patients with relapsed CNS lymphoma.During the phase 1 portion of the study, the investigators will examine three dose levels of Lenalidomide (10mg, 15mg and 20mg) in combination with Tafasitamab at a dose of 12 mg/kg. After MTD/RP2D is determined during phase 1, the phase 2 portion of the study will begin enrollment to the established dose.

Participants will be followed for AEs 90 days after last dose/decision to discontinue treatment, or new treatments are administered and followed for overall survival/disease status for up to 1 year after last dose. Participants may continue study treatment until disease progression.

Being tested
Tafasitamab, Lenalidomide

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TafasitamabDrug

    Also called MOR208

    Given IV

  • LenalidomideDrug

    Also called Revlimid

    Given Orally

Study groups in NCT05351593
Study groupRoleWhat they receive
Phase 1 (Tafasitamab, Lenalidomide)ExperimentalParticipants 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.
Receives: Drug: Tafasitamab; Drug: Lenalidomide
Phase 2 (Tafasitamab, Lenalidomide)ExperimentalParticipants 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.
Receives: Drug: Tafasitamab; Drug: Lenalidomide

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Toxicities will be classified using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The DLT will be based on the tolerability observed during the first cycle. In order for a patient to be assessed for DLT, they must receive at least 75% of lenalidomide dose (16 of the planned 21 days of lenalidomide administration). The maximum tolerated dose of lenalidomide/Tafasitamab will be the highest dose at which fewer than one-third of patients experience dose limiting toxicity. If multiple toxicities are seen, the presence of dose limiting toxicity should be based on the most severe toxicity experienced.

    Measured: Up to 1 cycle (1 cycle is equal to 28 days)

  2. Maximum Tolerated Dose (MTD) (Phase 1)

    The MTD is the highest dose at which no more than one instance of a DLT is observed among 6 participants treated.

    Measured: Up to 1 cycle (1 cycle is equal to 28 days)

  3. Recommended Phase 2 Dose (RP2D) (Phase1)

    The RP2D is the dose at which the Phase 2 portion of the study will begin enrolling. RP2D will be determined based on all data including available pharmacokinetics (PK), pharmacodynamic (PD), target engagement, efficacy, safety and tolerability data collected during Phase 1

    Measured: Up to 1 cycle (1 cycle is equal to 28 days)

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

    Response to the combination lenalidomide/Tafasitamab treatment is defined as achieving clinical benefit better at three months restaging. That is overall tumor shrinkage within three months of treatment initiation or stable disease at three months restaging. Response criteria will be graded using the Cytologic Response Criteria, Neurologic Response Criteria, and Radiographic Response Criteria developed by the International Workshop to Standardize Baseline Evaluation and Response Criteria in Primary CNS Lymphoma The response rate is defined as the proportion of study participants meeting the definition of response in Efficacy Analysis Set (EAS). Response rate will be summarized by percentage, along with the corresponding exact 95% confidence intervals (CIs).

    Measured: Up to 3 months

Secondary outcomes (3)

  1. Proportion of participants with Treatment-Related Adverse Events

    Serious adverse events, adverse events which are >=Grade 3, and adverse events resulting in discontinuation of treatment, withdrawal from the study, and deaths on-study will be used to determine the proportion of participants with treatment-related adverse events. Analyses will be performed based on the safety population.

    Measured: Up to 90 days

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

    PFS is defined as the duration from first dose to disease relapse, progression, or death, whichever occurs first. The censoring time for PFS is set to be last study assessment for progression, and will be descriptively analyzed using Kaplan-Meier methods

    Measured: Up to 1 year

  3. Median Overall Survival (OS)

    OS is defined as the duration from first dose to death. The censoring time for OS is set to be the last study contact. OS will be descriptively analyzed using Kaplan-Meier methods.

    Measured: Up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Apr 2022
  2. Study start8 Jun 2022
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion30 Sep 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
35 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05351593
Sponsor's protocol ID
212531
Other IDs
NCI-2022-03704
Status last verified
Jun 2026
First submitted
22 Apr 2022
Last updated
14 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Tafasitamab and Lenalidomide in people with CNS Lymphoma and Primary Central Nervous System Lymphoma, run by James Rubenstein at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 14 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact UCSF Hematopoietic Malignancies Clinical Trial Recruitment (877-827-3222, HDFCCC.Heme@ucsf.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of participants with dose limiting toxicities (DLTs) (Phase 1) (time frame: Up to 1 cycle (1 cycle is equal to 28 days)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05351593.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2026.

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