Relapsed/Refractory Aggressive B-Cell MalignanciesPhase 1/2NCT05588440
A Clinical Study of ONCT-808 in Subjects With Relapsed or Refractory B-Cell Malignancies
A Phase 1/2 study testing ONCT-808 and Bridging Therapy in people with Relapsed/Refractory Aggressive B-Cell Malignancies, run by Oncternal Therapeutics, Inc at 4 sites in United States.
Trial summary
This is a Phase 1/2 study to investigate the safety and efficacy of the CAR-T therapy, ONCT-808, in patients with relapsed/refractory (R/R) aggressive B cell malignancies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed/Refractory Aggressive B-Cell Malignancies
- What is being tested?
- ONCT-808 and Bridging Therapy
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 4 sitesUnited States
- Study dates
- 9 May 2023to 12 Sep 2024
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Over 18 years old
- Histologically confirmed aggressive B-cell NHL, including:
- MCL, with diagnosis confirmed by cyclin D1 overexpression or evidence of t (11;14) translocation
- LBCL, including:
- DLBCL NOS
- Primary mediastinal LBCL
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- High-grade BCL
- DLBCL arising from follicular lymphoma
- Follicular lymphoma grade 3B
- Richter's syndrome
- Availability of archival tissue for immunohistology, or willing to undergo baseline biopsy if not available
- R/R with no available therapy. Subject must have:
- Received prior systemic therapy that has included an alkylating agent, anthracycline, and an anti-CD20 mAb
- Received and progressed after autologous hematopoietic stem cell transplant (HSCT) or is ineligible for or has refused to receive HSCT
- Received prior approved CD19 CAR T-cell therapy or is ineligible for or has refused CD19 CAR-T
- Minimum washout period between previous systemic therapy and leukapheresis includes:
- Chemotherapy: at least 14 days or 5 half-lives, whichever is shorter
- Autologous HSCT: at least 3 months
- CD19 CAR T-cell therapy: at least 6 months
- ≥1 measurable lesion per Lugano criteria (Cheson, 2014)
- Subject has Fluorodeoxyglucose (FDG)-avid disease.
- Subject has an ECOG performance status of 0 or 1.
- Subject has adequate organ function:
- ALC ≥100/uL
- ANC ≥1000/uL (≥500/uL if due to lymphoma; growth factors allowed)
- Hgb ≥8 g/dL (transfusion allowed)
- Platelets ≥75,000/uL (≥50,000/uL if due to lymphoma; transfusion allowed)
- CrCL ≥50 ml/min; AST/ALT ≤2.5x ULN, T. bili ≤1.5 mg/dl (except Gilbert's)
- EF ≥50% by ECHO/MUGA; NCS ECG, NCS pleural effusion; O2 sat >92%
- Subject has an estimated life expectancy of >12 weeks
Who cannot join
- Prior ROR1-targeted therapy
- Current or anticipated systemic immunosuppressive therapy (e.g., prednisone >5 mg) from LD chemo until Day 28 post ONCT-808 dosing
- If receiving anticoagulation therapy, subject is unable to hold therapy for 3 days prior and 28 days following ONCT-808 administration
- Known CNS involvement by malignancy within 6 months
- H/o or current CNS disorder (e.g., seizure, CVA, dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy syndrome or any autoimmune disease with CNS involvement) within 6 months of study entry
- Clinically significant cardiovascular disease (e.g., MI, UA, CABG, or CHF grade ≥2 NYHA within 12 months of planned ONCT-808 dosing) or serious arrhythmia requiring medication
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- Evidence of HIV infection or active HBV, HCV
- Systemic fungal infection requiring medication in the last 12 months
- H/o Covid-19 infection with residual lung infiltrate/fibrosis
- H/o other malignancy except non-melanoma skin cancer or carcinoma in situ not in remission for ≥2 years
- H/o autoimmune disease resulting in end organ injury or require systemic immunosuppression within last 2 years
- H/o allogeneic HSCT or organ transplant
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
City of Hope National Medical Center
Duarte, California, 91010
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Phase 1/2 Multi-Center Study to Evaluate the Safety and Efficacy of ONCT-808 in Adult Subjects With Relapsed or Refractory Aggressive B-Cell Malignancies
This is a Phase 1/2 study to investigate the safety and efficacy of the CAR-T therapy, ONCT-808, in patients with relapsed/refractory (R/R) aggressive B cell malignancies.
Read the detailed description
Study ONCT-808-101 is a Phase 1/2, single-arm, open-label, multi-center study to evaluate the safety and tolerability, pharmacokinetics, and anti-tumor activity of ONCT-808 in subjects with aggressive B cell lymphoma (BCL), including large B-cell lymphoma (LBCL) and mantle cell lymphoma (MCL). The study will be separated into two distinct phases designated as Phase 1 and Phase 2.
After the safety and tolerability of ONCT-808 have been assessed to select the recommended Phase 2 dose (RP2D) in Phase 1, Phase 2 will commence to further validate the dose and evaluate the safety and efficacy of ONCT-808. In Phase 2, subjects with LBCL or MCL will be enrolled into 2 separate dose expansion cohorts.
- Being tested
- ONCT-808, Bridging Therapy
- Keywords
- Lymphoma, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Mantle Cell, Lymphoproliferative Disorders, Lymphatic Diseases, Immunoproliferative Disorders, Immune System Diseases, Lymphoma, Non-Hodgkin, ROR1, CAR-T cell therapy, Autologous CAR-T cell therapy, Adoptive cellular therapy, Cellular immunotherapy
- Medical subject headings
- Recurrence, Lymphoma, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Mantle-Cell, Lymphoproliferative Disorders, Lymphatic Diseases, Immunoproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ONCT-808Biological
A single infusion of ONCT-808 autologous CAR-T cell infusion will be administered intravenously
Phase 1: Dose Escalation with bridging therapy as needed
Phase 2: Patients with LBCL or MCL will be enrolled into two separate dose expansion cohorts.
Bridging TherapyDrug
Bridging therapy can be oral chemotherapy or IV radiotherapy/chemotherapy per institution's guidelines
| Study group | Role | What they receive |
|---|---|---|
| Phase 1: Dose Escalation | Experimental | Patients will receive a conditioning regimen of cyclophosphamide and fludarabine intravenously (IV) followed by ONCT-808 IV infusion escalated sequentially with a target dose consistent with the dose required by cohort being enrolled to determine Phase 2 dose (RP2d) regimen(s). Participants may receive bridging therapy that is appropriate to the subject's disease and treatment history if clinically indicated to maintain disease stability. Receives: Biological: ONCT-808; Drug: Bridging Therapy |
| Phase 2: Dose Expansion | Experimental | Patients with LBCL or MCL will receive ONCT-808 for each RP2D regimen determined in Phase 1. Receives: Biological: ONCT-808; Drug: Bridging Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
To Evaluate the Incidence of Dose Limiting Toxicities (DLT)
This is based on subject treated with ONCT-808. ONCT-808 1x10^6 CAR T cells/kg: n=3 ONCT-808 3x10^6 CAR T cells/kg: n=1 ONCT-808 0.3x10^6 CAR T cells/kg: n=2
Measured: Up to 28 days after the one-time infusion of ONCT-808
Secondary outcomes (1)
Best Metabolic Response Rate Post-Baseline
This is based on subject treated with ONCT-808. ONCT-808 1x10^6 CAR T cells/kg: n=3 ONCT-808 3x10^6 CAR T cells/kg: n=1 ONCT-808 0.3x10^6 CAR T cells/kg: n=2
Response assessments were evaluated using fluorodeoxyglucose (FDG) positron-emission tomography-computed tomography (PET-CT) per the Lugano classification (Cheson, 2014)
Measured: up to 1 year after the one-time infusion of ONCT-808
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2022
- Study start9 May 2023
- Primary completion12 Sep 2024
- Study completion12 Sep 2024
Why it stopped: Based on the available clinical data and capital requirements for continued development, the Company has decided to terminate this study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Relapsed/Refractory Aggressive B-Cell MalignanciesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Sequential
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oncternal Therapeutics, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michael Wang, Principal investigator, MD AndersonMatthew Wei, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05588440
- Sponsor's protocol ID
- ONCT-808-101
- Status last verified
- Nov 2024
- First submitted
- 23 Sep 2022
- Last updated
- 5 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/2 Multi-Center Study to Evaluate the Safety and Efficacy of ONCT-808 in Adult Subjects With Relapsed or Refractory Aggressive B-Cell Malignancies
- ClinicalTrials.gov ID
- NCT05588440
- Acronym / sponsor ID
- ONCT-808-101
- Keywords
- Lymphoma, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Mantle Cell, Lymphoproliferative Disorders, Lymphatic Diseases, Immunoproliferative Disorders, Immune System Diseases
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Based on the available clinical data and capital requirements for continued development, the Company has decided to terminate this study.
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Oncternal Therapeutics, IncIndustry (pharma, biotech, devices)
- Study start
- 9 May 2023 (actual)
- Primary completion
- 12 Sep 2024 (actual)
- Study completion
- 12 Sep 2024 (actual)
- First posted
- 20 Oct 2022 (actual)
- Results
- Posted 5 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 1/2 study to investigate the safety and efficacy of the CAR-T therapy, ONCT-808, in patients with relapsed/refractory (R/R) aggressive B cell malignancies.
Detailed description
Study ONCT-808-101 is a Phase 1/2, single-arm, open-label, multi-center study to evaluate the safety and tolerability, pharmacokinetics, and anti-tumor activity of ONCT-808 in subjects with aggressive B cell lymphoma (BCL), including large B-cell lymphoma (LBCL) and mantle cell lymphoma (MCL). The study will be separated into two distinct phases designated as Phase 1 and Phase 2.
After the safety and tolerability of ONCT-808 have been assessed to select the recommended Phase 2 dose (RP2D) in Phase 1, Phase 2 will commence to further validate the dose and evaluate the safety and efficacy of ONCT-808. In Phase 2, subjects with LBCL or MCL will be enrolled into 2 separate dose expansion cohorts.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase 1: Dose Escalation | Experimental | Biological: ONCT-808, Drug: Bridging TherapyPatients will receive a conditioning regimen of cyclophosphamide and fludarabine intravenously (IV) followed by ONCT-808 IV infusion escalated sequentially with a target dose consistent with the dose required by cohort being enrolled to determine Phase 2 dose (RP2d) regimen(s). Participants may receive bridging therapy that is appropriate to the subject's disease and treatment history if clinically indicated to maintain disease stability. |
| Phase 2: Dose Expansion | Experimental | Biological: ONCT-808, Drug: Bridging TherapyPatients with LBCL or MCL will receive ONCT-808 for each RP2D regimen determined in Phase 1. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- Over 18 years old
- Histologically confirmed aggressive B-cell NHL, including:
- Availability of archival tissue for immunohistology, or willing to undergo baseline biopsy if not available
- R/R with no available therapy. Subject must have:
- Minimum washout period between previous systemic therapy and leukapheresis includes:
Key exclusion criteria (12 listed)
- Prior ROR1-targeted therapy
- Current or anticipated systemic immunosuppressive therapy (e.g., prednisone >5 mg) from LD chemo until Day 28 post ONCT-808 dosing
- If receiving anticoagulation therapy, subject is unable to hold therapy for 3 days prior and 28 days following ONCT-808 administration
- Known CNS involvement by malignancy within 6 months
- H/o or current CNS disorder (e.g., seizure, CVA, dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy syndrome or any autoimmune disease with CNS involvement) within 6 months of study entry
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ONCT-808A single infusion of ONCT-808 autologous CAR-T cell infusion will be administered intravenously Phase 1: Dose Escalation with bridging therapy as needed Phase 2: Patients with LBCL or MCL will be enrolled into two separate dose expansion cohorts. | Biological | Phase 1: Dose Escalation, Phase 2: Dose Expansion |
| Bridging TherapyBridging therapy can be oral chemotherapy or IV radiotherapy/chemotherapy per institution's guidelines | Drug | Phase 1: Dose Escalation, Phase 2: Dose Expansion |
Primary outcome
To Evaluate the Incidence of Dose Limiting Toxicities (DLT)
Time frame: Up to 28 days after the one-time infusion of ONCT-808
This is based on subject treated with ONCT-808. ONCT-808 1x10^6 CAR T cells/kg: n=3 ONCT-808 3x10^6 CAR T cells/kg: n=1 ONCT-808 0.3x10^6 CAR T cells/kg: n=2
1 secondary outcome
Best Metabolic Response Rate Post-Baseline
Time frame: up to 1 year after the one-time infusion of ONCT-808
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Wang principal investigator
MD Anderson
Matthew Wei principal investigator
City of Hope Medical Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ONCT-808 and Bridging Therapy in people with Relapsed/Refractory Aggressive B-Cell Malignancies, run by Oncternal Therapeutics, Inc at 4 sites 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 30 inclusion and 12 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: stopped early, as of the sponsor's last update on 5 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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?
Yes. Results are posted in the registry (first posted 5 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
To Evaluate the Incidence of Dose Limiting Toxicities (DLT) (time frame: Up to 28 days after the one-time infusion of ONCT-808). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Dec 2024.