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Tafasitamab Plus Lenalidomide in Relapsed CNS Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05351593
Recruitment Status : Not yet recruiting
First Posted : April 28, 2022
Last Update Posted : April 28, 2022
Sponsor:
Collaborator:
Incyte Corporation
Information provided by (Responsible Party):
James Rubenstein, University of California, San Francisco

Brief 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 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.

Condition or disease Intervention/treatment Phase
CNS Lymphoma Primary Central Nervous System Lymphoma Secondary Central Nervous System Lymphoma Drug: Tafasitamab Drug: Lenalidomide Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Tafasitamab Plus Lenalidomide in Relapsed CNS Lymphoma
Estimated Study Start Date : July 1, 2022
Estimated Primary Completion Date : April 30, 2023
Estimated Study Completion Date : April 30, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Phase 1 (Tafasitamab, Lenalidomide)
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.
Drug: Tafasitamab
Given IV
Other Name: MOR208

Drug: Lenalidomide
Given Orally
Other Name: Revlimid

Experimental: Phase 2 (Tafasitamab, Lenalidomide)
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.
Drug: Tafasitamab
Given IV
Other Name: MOR208

Drug: Lenalidomide
Given Orally
Other Name: Revlimid




Primary Outcome Measures :
  1. Proportion of participants with dose limiting toxicities (DLTs) (Phase 1) [ Time Frame: Up to 1 cycle (1 cycle is equal to 28 days) ]
    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.

  2. Maximum Tolerated Dose (MTD) (Phase 1) [ Time Frame: Up to 1 cycle (1 cycle is equal to 28 days) ]
    The MTD is the highest dose at which no more than one instance of a DLT is observed among 6 participants treated.

  3. Recommended Phase 2 Dose (RP2D) (Phase1) [ Time Frame: Up to 1 cycle (1 cycle is equal to 28 days) ]
    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

  4. Percentage of participants with demonstrated Clinical Benefit Rate (CBR) (Phase 2) [ Time Frame: Up to 3 months ]
    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).


Secondary Outcome Measures :
  1. Proportion of participants with Treatment-Related Adverse Events [ Time Frame: Up to 90 days ]
    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.

  2. Median Progression-free survival (PFS) (Phase 2) [ Time Frame: Up to 1 year ]
    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

  3. Median Overall Survival (OS) [ Time Frame: Up to 1 year ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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).

    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 109/ L (1,500/ microliter (mcL), growth factors permitted).
    2. Platelets ≥ 50 X 109 / 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.

    d. Creatinine clearance (CrCl, calculated) >= 60 mL/min/1.73 m2, 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.

7. Ability to understand and the willingness to sign a written informed consent document.

8. For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.

9. 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.

10. 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.

11. 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.

12. 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.

    13. Recipients of prior hematopoietic stem cell transplant are eligible as long as the following criteria are met:

a. Absence of graft versus host disease. b. Discontinuation of systemic immunosuppressant therapy.

Exclusion Criteria:

  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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05351593


Contacts
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Contact: Kate Rafanova (415) 502-4751 kate.rafanova@ucsf.edu

Locations
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United States, California
University of California, San Francisco
San Francisco, California, United States, 94143
Contact: Kate Rafanova    415-502-4751    kate.rafanova@ucsf.edu   
Contact    877-827-3222    cancertrials@ucsf.edu   
Principal Investigator: James Rubenstein, MD, PhD         
Sponsors and Collaborators
James Rubenstein
Incyte Corporation
Investigators
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Principal Investigator: James Rubenstein, MD, PhD University of California, San Francisco
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Responsible Party: James Rubenstein, Principal Investigator, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT05351593    
Other Study ID Numbers: 212531
NCI-2022-03704 ( Registry Identifier: NCI Clinical Trials Reporting Program (CTRP) )
First Posted: April 28, 2022    Key Record Dates
Last Update Posted: April 28, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lenalidomide
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents