RECRUITING

Tafasitamab Plus Lenalidomide in Relapsed CNS Lymphoma

Conditions

CNS Lymphoma Primary Central Nervous System Lymphoma Secondary Central Nervous System Lymphoma

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2022-06-08

Study Completion:2026-06-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05351593

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. 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). 1. Concomitant systemic lymphoma as well as transformation from follicular lymphoma and/or Chronic lymphocytic leukemia (CLL) to an aggressive B-cell histology is allowed. 2. Participants are eligible with disease in each CNS compartment: brain, leptomeninges/CSF and intraocular compartment. 2. Age \>= 18 years. 3. Anticipated survival \> 2 months, as determined by the investigator. 4. Eastern Cooperative Oncology Group (ECOG) performance status \<=1 (Karnofsky performance status \>= 70%) 5. Demonstrates adequate organ function as defined below: 1. Absolute neutrophil count (ANC) ≥ 1.5 X 10\^9/ L (1,500/ microliter (mcL), growth factors permitted). 2. Platelets \>= 50 X 10\^9 / L (50,000/ mcL, platelet transfusion independent). 3. Total bilirubin \<= 1.5 x institutional upper limit of normal,unless elevated due to Gilbert's syndrome. 4. Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) \<=3 X institutional upper limit of normal. 5. Alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) \<=3 X institutional upper limit of normal. 6. Ability to understand and the willingness to sign a written informed consent document. 7. 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 PCR to confirm. 8. 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. 9. 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. 10. 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. 11. Prior Therapies 1. Participants with CNS lymphoma involving the brain parenchyma must have received at least one prior systemic therapy. 2. Participants with secondary CNS lymphoma must have received prior CNS-directed treatment. 3. 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. 12. Recipients of prior hematopoietic stem cell transplant are eligible as long as the following criteria are met: 1. Absence of graft versus host disease. 2. Discontinuation of systemic immunosuppressant therapy.	1. Has received systemic anti-cancer therapies within 2 weeks of first dose, radiation within 1 week, antibody therapy within 4 weeks. 2. Has not recovered from adverse events due to prior anti-cancer therapy to ≤ grade 1 or baseline (other than alopecia). 3. Is currently receiving any other investigational agents. 4. 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. 5. Has a history of HIV infection. 6. Has CNS post-transplant lymphoproliferative disease (PTLD). 7. Has known hypersensitivity to lenalidomide or Tafasitamab. 8. 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. 9. Prior receipt of anti-CD19 based therapy including anti-CD19, Chimeric antigen receptor T cells (CAR-T) therapy is an exclusion criteria. 10. Has any significant medical condition or comorbidity that could compromise patient safety (e.g., uncontrolled serious infection).

Inclusion Criteria

Exclusion Criteria

1. 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).
1. Concomitant systemic lymphoma as well as transformation from follicular lymphoma and/or Chronic lymphocytic leukemia (CLL) to an aggressive B-cell histology is allowed.
2. Participants are eligible with disease in each CNS compartment: brain, leptomeninges/CSF and intraocular compartment.
2. Age \>= 18 years.
3. Anticipated survival \> 2 months, as determined by the investigator.
4. Eastern Cooperative Oncology Group (ECOG) performance status \<=1 (Karnofsky performance status \>= 70%)
5. Demonstrates adequate organ function as defined below:
1. Absolute neutrophil count (ANC) ≥ 1.5 X 10\^9/ L (1,500/ microliter (mcL), growth factors permitted).
2. Platelets \>= 50 X 10\^9 / L (50,000/ mcL, platelet transfusion independent).
3. Total bilirubin \<= 1.5 x institutional upper limit of normal,unless elevated due to Gilbert's syndrome.
4. Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) \<=3 X institutional upper limit of normal.
5. Alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) \<=3 X institutional upper limit of normal.
6. Ability to understand and the willingness to sign a written informed consent document.
7. 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 PCR to confirm.
8. 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.
9. 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.
10. 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.
11. Prior Therapies
1. Participants with CNS lymphoma involving the brain parenchyma must have received at least one prior systemic therapy.
2. Participants with secondary CNS lymphoma must have received prior CNS-directed treatment.
3. 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.
12. Recipients of prior hematopoietic stem cell transplant are eligible as long as the following criteria are met:
1. Absence of graft versus host disease.
2. Discontinuation of systemic immunosuppressant therapy.

1. Has received systemic anti-cancer therapies within 2 weeks of first dose, radiation within 1 week, antibody therapy within 4 weeks.
2. Has not recovered from adverse events due to prior anti-cancer therapy to ≤ grade 1 or baseline (other than alopecia).
3. Is currently receiving any other investigational agents.
4. 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.
5. Has a history of HIV infection.
6. Has CNS post-transplant lymphoproliferative disease (PTLD).
7. Has known hypersensitivity to lenalidomide or Tafasitamab.
8. 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.
9. Prior receipt of anti-CD19 based therapy including anti-CD19, Chimeric antigen receptor T cells (CAR-T) therapy is an exclusion criteria.
10. Has any significant medical condition or comorbidity that could compromise patient safety (e.g., uncontrolled serious infection).

Contacts and Locations

Study Contact

Morgan Tate

CONTACT

877-827-3222

Morgan.Tate@ucsf.edu

Principal Investigator

James Rubenstein, MD, PhD

PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Study Locations (Sites)

University of California, San Francisco

San Francisco, California, 94143

United States

Collaborators and Investigators

Sponsor: James Rubenstein

James Rubenstein, MD, PhD, PRINCIPAL_INVESTIGATOR, University of California, San Francisco

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-06-08

Study Completion Date2026-06-30

Study Record Updates

Study Start Date2022-06-08

Study Completion Date2026-06-30

Terms related to this study

Additional Relevant MeSH Terms

CNS Lymphoma
Primary Central Nervous System Lymphoma
Secondary Central Nervous System Lymphoma