NCT05910801

Brief Summary

This phase II trial tests how well tafasitamab, lenalidomide and venetoclax work in treating patients with mantle cell lymphoma that has come back (after a period of improvement) (relapsed) or that has not responded to previous treatment (refractory). Tafasitamab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Lenalidomide is in a class of medications called immunomodulatory agents. It works by helping the immune system kill cancer cells. Venetoclax is in a class of medications called B-cell lymphoma-2 (Bcl-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving tafasitamab, lenalidomide and venetoclax together may kill cancer cells more efficiently in patients with relapsed or refractory mantle cell lymphoma.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
100

participants targeted

Target at P50-P75 for phase_2

Timeline
56mo left

Started Jan 2024

Longer than P75 for phase_2

Geographic Reach
1 country

2 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress34%
Jan 2024Dec 2030

First Submitted

Initial submission to the registry

June 9, 2023

Completed
11 days until next milestone

First Posted

Study publicly available on registry

June 20, 2023

Completed
7 months until next milestone

Study Start

First participant enrolled

January 4, 2024

Completed
6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 30, 2029

Expected
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

December 30, 2030

Last Updated

November 18, 2024

Status Verified

November 1, 2024

Enrollment Period

6 years

First QC Date

June 9, 2023

Last Update Submit

November 14, 2024

Conditions

Outcome Measures

Primary Outcomes (1)

  • Objective response rate

    A response is defined to be either a partial metabolic response (PMR) or complete metabolic response (CMR) by positron emission tomography (PET) or a partial response (PR) or complete response (CR) by computed tomography (CT) noted as the objective status using Lugano criteria. Objective response rate is defined as the proportion of evaluable patients who achieve response while on treatment. Estimate and corresponding 95% confidence intervals will be calculated according to the approach of Duffy and Santner.

    Up to 5 years

Secondary Outcomes (5)

  • Complete response rate

    Up to 5 years

  • Duration of response

    From first documentation of objective status(PMR or CMR by PET/CT, or PR or CR by CT) to the earliest date of progression or death, assessed up to 5 years

  • Progression free survival

    From registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 5 years

  • Overall survival

    From registration to death due to any cause, assessed up to 5 years

  • Incidence of adverse events (AE)

    Up to 5 years

Study Arms (1)

Treatment (Tafasitamab, lenalidomide, venetoclax)

EXPERIMENTAL

Patients receive tafasitamab IV, lenalidomide PO and venetoclax PO while on study. Patients may undergo lumbar puncture during screening. Patients undergo CT scan and blood sample collection and may undergo MRI and tumor biopsy on study and during follow-up. Patients undergo PET/CT, bone marrow biopsy, and bone marrow aspirate throughout the study.

Procedure: BiopsyProcedure: Biospecimen CollectionProcedure: Bone Marrow AspirationProcedure: Bone Marrow BiopsyProcedure: Computed TomographyDrug: LenalidomideProcedure: Lumbar PunctureProcedure: Magnetic Resonance ImagingProcedure: Positron Emission TomographyBiological: TafasitamabDrug: Venetoclax

Interventions

BiopsyPROCEDURE

Undergo biopsy

Also known as: BIOPSY_TYPE, Bx
Treatment (Tafasitamab, lenalidomide, venetoclax)

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection
Treatment (Tafasitamab, lenalidomide, venetoclax)

Undergo bone marrow aspiration

Treatment (Tafasitamab, lenalidomide, venetoclax)

Undergo bone marrow biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow
Treatment (Tafasitamab, lenalidomide, venetoclax)

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography
Treatment (Tafasitamab, lenalidomide, venetoclax)

Given PO

Also known as: CC-5013, CC5013, CDC 501, Revlimid
Treatment (Tafasitamab, lenalidomide, venetoclax)

Undergo lumbar puncture

Also known as: LP, Spinal Tap
Treatment (Tafasitamab, lenalidomide, venetoclax)

Undergo MRI

Also known as: Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging
Treatment (Tafasitamab, lenalidomide, venetoclax)

Undergo PET/CT scan

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT
Treatment (Tafasitamab, lenalidomide, venetoclax)
TafasitamabBIOLOGICAL

Given IV

Also known as: Immunoglobulin, Anti-(Human Cd19 Antigen) (Human-mus musculus Monoclonal MOR00208 Heavy Chain), Disulfide with Human-mus musculus Monoclonal MOR00208 .Kappa.-chain, Dimer, Monjuvi, MOR-00208, MOR00208, MOR208, Tafasitamab-cxix, XmAb5574
Treatment (Tafasitamab, lenalidomide, venetoclax)

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto
Treatment (Tafasitamab, lenalidomide, venetoclax)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age \>= 18 years old
  • Confirmed pathology diagnosis of mantle cell lymphoma (MCL) with t(11;14)(q13;q32) translocation or cyclin D1 overexpression NOTE: Patients with relapsed/refractory MCL after prior anti-CD19 therapy (such as chimeric antigen receptor \[CAR\] T-cell therapy) should have confirmed preserved expression of CD19, unless a biopsy is not feasible or associated with a high risk of complications in the treating physician's opinion
  • Relapsed or refractory disease, which is defined as patients with \>= 1 line of prior systemic treatment NOTE: Prior exposure to lenalidomide or venetoclax is allowed, provided there was no disease progression on lenalidomide or venetoclax
  • In the view of the treating physician, the patient is in need of treatment, for example, with lymphoma-related symptoms or cytopenia
  • Evaluable disease, which is defined as at least one lymph node or other type of lesion that has a size \>= 1.5 cm, or spleen size \>= 15 cm or white blood cell (WBC) \>= 30,000/mm\^3 in leukemic non-nodal MCL patients
  • Eastern Cooperative Oncology Group Performance Status (PS) 0, 1, or 2
  • Absolute neutrophil count (ANC) \>= 1500/mm\^3 (obtained =\< 14 days prior to registration)
  • Platelet count \>= 75,000/mm\^3 (\>= 50,000/mm\^3 if there is evidence of bone marrow involvement by MCL or hypersplenism) (obtained =\< 14 days prior to registration)
  • Hemoglobin \> 8.0 g/dL (obtained =\< 14 days prior to registration)
  • Activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) =\< 1.5 × upper normal limit (ULN) (obtained =\< 14 days prior to registration)
  • Prothrombin (PT) or international normalized ratio (INR) =\< 1.5 × upper normal limit (ULN) (obtained =\< 14 days prior to registration)
  • Total bilirubin =\< 1.5 × ULN (or =\< 3 × ULN if there is evidence of parenchymal liver involvement with MCL or documented Gilbert's disease) (obtained =\< 14 days prior to registration)
  • Alanine aminotransferase (ALT) and aspartate transaminase (AST) =\< 3 × ULN (or =\< 5 × ULN if there is evidence of parenchymal liver involvement with MCL) (obtained =\< 14 days prior to registration)
  • Calculated creatinine clearance \> 60 ml/min using the Cockcroft-Gault formula (obtained =\< 14 days prior to registration)
  • Negative pregnancy test done =\< 7 days prior to registration, for women of reproductive potential only NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required NOTE: Females of reproductive potential include all females who are menstruating, amenorrheic from previous medical treatments, under 50 years of age, and/or perimenopausal, and do not qualify for the females not of reproductive potential category. Females not of reproductive potential include females who have been in natural menopause for at least 24 consecutive months, or who have had a hysterectomy and/or bilateral oophorectomy, or female children who have not started menstruating
  • +6 more criteria

You may not qualify if:

  • Any of the following:
  • Pregnant persons
  • Nursing persons (lactating persons are eligible provided that they agree not to use their breast milk to feed while receiving treatment on the study or within 3 months of the last dose of study treatment)
  • Men or women of reproductive potential who are unwilling to employ adequate contraception during treatment and for 4 weeks after last dose of lenalidomide or for 3 months after last dose of tafasitamab (whichever is longer)
  • Any of the following prior therapies:
  • Autologous stem cell transplant =\< 90 days prior to registration
  • Allogeneic stem cell transplant
  • Anti-CD19 CAR T-cell therapy =\< 90 days prior to registration
  • Any central nervous system (CNS) involvement by MCL (e.g., any parenchymal, leptomeningeal, cerebrospinal fluid \[CSF\], cranial or spinal nerve root involvement)
  • Receiving any other treatment which would be considered as a treatment for MCL (with the exception of corticosteroid). If a patient received recent MCL treatment prior to registration, at least 5 half-lives of the drug(s) OR 14 days must have passed following the last dose for the patient to be eligible
  • Any of the following medication requirement or recent use:
  • Anticoagulation with a vitamin K antagonist =\< 7 days prior to registration
  • Requirement of a P-gp inhibitor during the study
  • Requirement of a strong cytochrome P450 (CYP) 3A inhibitor or inducer during the study
  • Use of a strong or moderate CYP3A inhibitor or inducer =\< 7 days prior to registration
  • +26 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

M D Anderson Cancer Center

Houston, Texas, 77030, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

BiopsySpecimen HandlingLenalidomideSpinal PunctureMagnetic Resonance SpectroscopytafasitamabImmunoglobulinsDisulfidesvenetoclax

Condition Hierarchy (Ancestors)

Lymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

CytodiagnosisCytological TechniquesClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisDiagnostic Techniques, SurgicalSurgical Procedures, OperativeInvestigative TechniquesPhthalimidesPhthalic AcidsAcids, CarbocyclicCarboxylic AcidsOrganic ChemicalsPiperidonesPiperidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsIsoindolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingDiagnostic Techniques, NeurologicalPuncturesTherapeuticsSpectrum AnalysisChemistry Techniques, AnalyticalImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsSulfidesAnionsIonsElectrolytesInorganic ChemicalsHydrogen SulfideSulfur Compounds

Study Officials

  • Yucai Wang

    Academic and Community Cancer Research United

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Inbox Mayo Clinic Cancer Studies

CONTACT

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 9, 2023

First Posted

June 20, 2023

Study Start

January 4, 2024

Primary Completion (Estimated)

December 30, 2029

Study Completion (Estimated)

December 30, 2030

Last Updated

November 18, 2024

Record last verified: 2024-11

Locations