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Recurrent Diffuse Large B-Cell LymphomaPhase 1NCT05228249

Loncastuximab Tesirine in Combination With Chemotherapy Prior to Stem Cell Transplant for the Treatment of Recurrent or Refractory Diffuse Large B-Cell Lymphoma

A Phase 1 study testing Autologous Hematopoietic Stem Cell Transplantation, Carmustine and Cytarabine in people with Recurrent Diffuse Large B-Cell Lymphoma and Recurrent Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, run by Fred Hutchinson Cancer Center at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This phase I trial studies the side effects and best dose of loncastuximab tesirine in combination with carmustine, etoposide, cytarabine, and melphalan (BEAM) chemotherapy regimen in treating patients with diffuse large B-cell lymphoma that has come back (recurrent) or has not responded to treatment (refractory). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Autologous Hematopoietic Stem Cell Transplantation, Carmustine and Cytarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
Apr 2023to 1 Oct 2027
Phase
Phase 1
Are there results?
None posted in the registry

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

  • PART 1: Subjects must have a histologically confirmed diagnosis of diffuse large B-cell lymphoma including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma (with MYC and BCL-2 and/or BCL-6 gene rearrangement), and DLBCL arising from follicular lymphoma
  • PART 1: Subjects must be eligible for high-dose therapy (BEAM conditioning chemotherapy) and autologous stem cell transplant, as determined by transplant center
  • PART 1: Subjects must have chemosensitive disease as defined radiographically (positron emission tomography [PET]/computed tomography [CT] and/or diagnostic CT) by at least a partial response (PR) to their last cycle of salvage therapy, within 60 days of enrollment
  • PART 1: Subjects must be >= 18 years of age
  • PART 1: Eastern Cooperative Oncology Group (ECOG) score =< 2 or Karnofsky score >= 60%
  • PART 1: Creatinine clearance (CrCl) > 40 mL/min by Cockcroft-Gault formula or serum creatinine =< 2.0 mg/dL
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  • PART 1: Total bilirubin =< 1.5 x the upper limit of normal (ULN) unless isolated hyperbilirubinemia attributed to Gilbert's syndrome; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN
  • PART 1: Adequate pulmonary function, defined as lung carbon monoxide diffusing capability test (DLCO) (corrected or uncorrected for hemoglobin per institutional standards), forced expiratory volume in 1 (FEV1), forced vital capacity (FVC) >= 50% of predicted
  • PART 1: Cardiac: Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) of >= 50%. Patients 60 years or older must have an LVEF at rest >= 40%, as measured by echocardiogram or radionuclide ventriculogram scan (MUGA)
  • PART 1: Hematologic: Prothrombin time (PT)/international normalized ratio (INR) < 1.5 x ULN and partial thromboplastin time PTT) (activated partial thromboplastin time [aPTT]) < 1.5 x ULN, absolute neutrophil count (ANC) >= 1000/mL, platelet >= 75,000/uL
  • PART 1: Women of childbearing potential (WOCBP), defined as those who have not been surgically sterilized or who have not been free of menses for at least 1 year, must have a negative serum pregnancy test within 7 days of and prior to initiating loncastuximab tesirine in combination with BEAM conditioning
  • Fertile male and WOCBP subjects must be willing to use highly effective contraceptive methods before, during, and for at least 6 months after ASCT or 9 months after the last administration of loncastuximab tesirine for women, 6 months after the last administration of loncastuximab tesirine for men, whichever is longer
  • PART 1: Ability to provide informed consent
  • PART 2: Eligible disease status. Following ASCT (within day +30 to +90), subjects must have achieved radiographic partial response (PR) or complete response (CR) via PET/CT and/or diagnostic CT
  • PART 2: Targeted radiation therapy following ASCT is allowed but must be completed >= 2 weeks prior to starting maintenance therapy
  • PART 2: Performance status ECOG 0-2 and/or Karnofsky >= 60
  • PART 2: CrCl > 40 mL/min by Cockcroft-Gault formula or serum creatinine =< 2.0 mg/dL
  • PART 2: Total bilirubin =< 1.5 x the upper limit of normal (ULN) unless isolated hyperbilirubinemia attributed to Gilbert's syndrome; AST and ALT =< 3 x ULN
  • PART 2: PT/INR < 1.5 x ULN and PTT (aPTT) < 1.5 x ULN, ANC >= 1000/mL, platelet >= 75,000/mL
  • PART 2: Pregnancy and the need for contraception. Negative serum pregnancy test within 7 days of initiating loncastuximab tesirine as maintenance therapy for women of childbearing potential (WOCBP), defined as those who have not been surgically sterilized or who have not been free of menses for at least 1 year
  • Fertile male and WOCBP patients must be willing to use highly effective contraceptive methods before, during, and for at least 6 months after ASCT or 16 weeks after the last administration of loncastuximab tesirine, whichever is longer

Who cannot join

  • PART 1: Receiving other investigational agents
  • PART 1: History of central nervous system (CNS) involvement by lymphoma
  • PART 1: If a history of receiving a CD19 targeting agent (e.g., CD19 directed CAR T-cell Kymriah, Yescarta, Breyanzi, CD19 antibody Monjuvi), must have pathologic evidence for CD19 expression after receiving CD19 targeting agent
  • PART 1: History of immunogenicity or hypersensitivity to a CD19 antibody
  • PART 1: Uncontrolled bacterial, viral or fungal infection (currently taking medication and with progression or no clinical improvement); symptomatic congestive heart failure unresponsive to treatment, unstable angina pectoris, symptomatic cardiac arrhythmia not including premature ventricular contractions (PVC); or psychiatric illness/social situations that would limit compliance with study requirements
  • PART 1: Active autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, Sjogren's syndrome, autoimmune vasculitis [e.g., granulomatosis with polyangiitis]); motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and myasthenia gravis); other central nervous system (CNS) autoimmune disease (e.g., poliomyelitis, multiple sclerosis)
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  • PART 1: Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath)
  • PART 1: Known seropositivity for human immunodeficiency virus (HIV), known history of hepatitis B or hepatitis C
  • PART 1: Active second primary malignancy other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy that the investigator(s) agreed and had documented that it was not exclusionary
  • PART 1: Any other significant medical illness, abnormality, or condition that could, in the investigator(s)' judgment, make the patient inappropriate for study participation or could put the patient at risk
  • PART 1: Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on bone marrow biopsy prior to initiation of therapy

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: Loncastuximab Tesirine in Combination With BEAM (Carmustine, Etoposide, Ara-C, Melphalan) Conditioning Regimen Prior to Autologous Stem Cell Transplant (ASCT) and for Maintenance Therapy in Diffuse Large B-Cell Lymphoma (DLBCL)

This phase I trial studies the side effects and best dose of loncastuximab tesirine in combination with carmustine, etoposide, cytarabine, and melphalan (BEAM) chemotherapy regimen in treating patients with diffuse large B-cell lymphoma that has come back (recurrent) or has not responded to treatment (refractory). Loncastuximab tesirine is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs, such as carmustine, etoposide, cytarabine, and melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy with loncastuximab tesirine may kill more cancer cells.

Read the detailed description

OUTLINE: This is a dose-escalation study of loncastuximab tesirine.

PART I (CONDITIONING): Patients receive loncastuximab tesirine intravenously (IV) on day -7, carmustine IV over 2 hours on day -7, etoposide IV over 1-2 hours twice daily (BID) days -6, -5, -4, and -3, cytarabine IV over 1 hour BID on days -6, -5, -4, and -3, and melphalan IV over 15-20 minutes on day -2. Patients undergo peripheral blood ASCT per standard practice on day 0.

PART II (MAINTENANCE): Beginning 30-90 days after ASCT, patients receive loncastuximab tesirine IV once every 3 weeks (Q3W) for up to 9 cycles in the absence of disease progression or unacceptable toxicity.

After completion of the study treatment, patients are followed for 2 years.

Being tested
Autologous Hematopoietic Stem Cell Transplantation, Carmustine, Cytarabine, Etoposide, Loncastuximab Tesirine
Medical subject headings
Lymphoma, Large B-Cell, Diffuse

What participants receive

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

  • Autologous Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called AHSCT, Autologous, Autologous Hematopoietic Cell Transplantation, Autologous Stem Cell Transplant

    Undergo peripheral blood ASCT

  • CarmustineDrug

    Also called BCNU, Becenum, Becenun, BiCNU

    Given IV

  • CytarabineDrug

    Also called .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone

    Given IV

  • EtoposideDrug

    Also called Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar

    Given IV

  • Loncastuximab TesirineBiological

    Also called ADC ADCT-402, ADCT-402, Anti-CD19 PBD-conjugate ADCT-402, Loncastuximab Tesirine-lpyl

    Given IV

  • MelphalanDrug

    Also called Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard

    Given IV

Study groups in NCT05228249
Study groupRoleWhat they receive
Treatment (loncastuximab tesirine, BEAM chemotherapy)ExperimentalPART I (CONDITIONING): Patients receive loncastuximab tesirine IV on day -7, carmustine IV over 2 hours on day -7, etoposide IV over 1-2 hours BID days -6, -5, -4, and -3, cytarabine IV over 1 hour BID on days -6, -5, -4, and -3, and melphalan IV over 15-20 minutes on day -2. Patients undergo peripheral blood ASCT per standard practice on day 0. PART II (MAINTENANCE): Beginning 30-90 days after ASCT, patients receive loncastuximab tesirine IV Q3V for up to 9 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Carmustine; Drug: Cytarabine; Drug: Etoposide; Biological: Loncastuximab Tesirine; Drug: Melphalan

What is being measured

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

  1. Incidence of dose-limiting toxicity (Part 1)

    Will be descriptive based on the appropriate analysis set and may include summary statistics such as means/median, standard deviations, range for continuous variables, and count/percentage for categorical variables, if applicable.

    Measured: Up to 30 days

  2. Incidence of toxicity requiring dose delay or modification (Part 2)

    Will be descriptive based on the appropriate analysis set and may include summary statistics such as means/median, standard deviations, range for continuous variables, and count/percentage for categorical variables, if applicable.

    Measured: Up to 30 days

Secondary outcomes (2)

  1. Progression-free survival

    Kaplan-Meier curves and median time-to-event estimation with 95% confidence intervals will be presented for time to-event endpoints, if appropriate.

    Measured: Time from receiving loncastuximab tesirine to the first observation of disease progression or death from any cause, whichever occurs first, assessed at 2 years post-autologous stem cell transplantation (ASCT)

  2. Overall survival

    Kaplan-Meier curves and median time-to-event estimation with 95% confidence intervals will be presented for time to-event endpoints, if appropriate.

    Measured: Time from receiving loncastuximab tesirine to death from any cause, assessed at 2 years post-ASCT

Timeline

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

  1. First posted8 Feb 2022
  2. Study startApr 2023 (estimated)
  3. Primary completion1 Oct 2025 (estimated)
  4. Study completion1 Oct 2027 (estimated)

Why it stopped: PI left institution and funding sponsor closed study. Study did not open to accrual, and no participants were enrolled.

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05228249
Sponsor's protocol ID
RG1121551
Other IDs
NCI-2021-14126, 10881
Status last verified
Jan 2023
First submitted
27 Jan 2022
Last updated
13 Jan 2023
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 study testing Autologous Hematopoietic Stem Cell Transplantation, Carmustine and Cytarabine in people with Recurrent Diffuse Large B-Cell Lymphoma and Recurrent Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, run by Fred Hutchinson Cancer Center 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 21 inclusion and 11 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: withdrawn, as of the sponsor's last update on 13 Jan 2023. 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 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.

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

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of dose-limiting toxicity (Part 1) (time frame: Up to 30 days). The study lists 2 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 NCT05228249.

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 13 Jan 2023.

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