Acute Myeloid LeukemiaPhase 1NCT04464889

HA-1H TCR T Cell for Relapsed/Persistent Hematologic Malignancies After Allogeneic Stem Cell Transplantation

A Phase 1 study testing MDG1021 dose 1, MDG1021 dose 2 and MDG1021 dose 3 in people with Acute Myeloid Leukemia and Acute Lymphoid Leukemia, run by Medigene AG at 1 site in Netherlands.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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Trial summary

This is a non-randomised, open-label phase I study of an investigational medicinal product (IMP) consisting of a HLA-A*02:01 restricted HA-1H T cell receptor transduced T cell (MDG1021) immunotherapy for relapsed or persistent hematologic malignancies after allogeneic hematopoietic stem cell transplantation. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Acute Myeloid Leukemia, Acute Lymphoid Leukemia, Myelodysplastic Syndromes
What is being tested?: MDG1021 dose 1, MDG1021 dose 2 and MDG1021 dose 3
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 0 participants
Where: 1 siteNetherlands
Study dates: 2 Jul 2020to Jul 2025
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

Relapsed or persistent disease is defined according to disease specific guidelines (AML, CML, MM, ALL, MDS, MPN, MF and malignant B- or T-cell lymphoma) and includes MRD positivity.
Patients positive for HLA-A*02:01 according to genotyping results
Patients positive for HA-1H
Patients who received the allo-HSCT at least 100 days preceding the leukapheresis
Patients (i.e. recipient) transplanted with a sibling or unrelated HSCT donor
donor being HLA-A*02:01 positive and HA-1H negative, or

Show all 12Show fewer

a donor with a single mismatch at HLA-A*02:01, being HA-1H positive or negative
Patients from whom at least 10x10^6 donor CD8+ T cells can be harvested by leukapheresis
Age ≥ 18 years, of either sex
ECOG performance status 0-2.
Life expectancy of at least 3 months
Patients must be able to understand and be willing to give signed informed consent

Who cannot join

Evidence of acute or chronic graft versus host disease (GVHD) ≥ grade II
Serologic evidence of acute or chronic hepatitis B virus infection (i.e. positive for HBsAg or IgM anti-HBc). Positive HIV and HCV serology or active bacterial infection
Medical or psychological conditions that would make the patient unsuitable candidate for cell therapy at the discretion of the investigator. Special risks to be considered:
Creatinine > 2.5 times the upper limit of normal (ULN) serum level
Total bilirubin, ALAT, ASAT > 3.0 x ULN serum level
Cardiac left ventricular ejection fraction < 35% at rest

Show all 22Show fewer

Severe restrictive or obstructive lung disease
Clinically significant and ongoing immune suppression including, but not limited to immunosuppressive agents (e.g. cyclosporine or corticosteroids (at an equivalent dose of ≥ 10 mg prednisone per day)). Inhaled steroid and physiological replacement for adrenal insufficiency is allowed
Patients with a history of primary immunodeficiency
Patients with a currently active second malignancy other than nonmelanoma skin cancers or subjects with history of prior malignancy and previously treated with a curative intent therapy less than 1 year ago
Patients both with urinary outflow obstructions and on dialysis or patients for whom cyclophosphamide is contraindicated for other reasons
Known or suspected hypersensitivity or intolerance to IMP, cyclophosphamide, fludarabine and/or tocilizumab or to any of the excipients
Participation in any clinical study < 60 days prior to first IMP administration in case of antibodies and < 14 days for all other IMPs
Vulnerable patients and/or patients unwilling or unable to comply with procedures required in this clinical study protocol
Pregnant or lactating women
Women of child-bearing potential not using highly effective method(s) of birth control (i.e., with low failure rate < 1% per year) throughout the study and/or unwilling to be tested for pregnancy. A negative serum β-hCG test is required at baseline
Fertile men not agreeing to use effective contraceptive methods during the clinical study
Uncontrolled central nervous system (CNS) disease
Uncontrolled, life threatening infections or uncontrolled disseminated intravascular coagulation; however, if these problems resolve, the start of treatment can be initiated on a delayed schedule
Evidence of acute or chronic graft versus host disease (GVHD) ≥ grade II
Unable to generate HA-1H TCR transduced T cells for transfusion (out of specification). However, if a lower than planned number of cells is available, the patient will have the option to receive the OOS HA-1H TCR transduced T cells product (cell dose must be at least the lowest dose level of D1 and will be analyzed in the safety and full analysis set populations.
If not enough starting material is collected during leukapheresis, the patient will be excluded from study participation and receive best available standard therapy.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

Leiden University Medical Centre
Leiden, South Holland, 2333 ZA Leiden

Other trials in Netherlands

About this study

Official title: A Dose-Escalation, Open Label Phase I Study to Assess the Safety, Feasibility and Preliminary Efficacy of HA-1H TCR Modified T Cells, MDG1021, in Patients With Relapsed or Persistent Hematologic Malignancies After Allogeneic HSCT With or Without Unmanipulated DLI

Read the detailed description

This phase I is designed to assess the safety and feasibility of a HLA-A*02:01 restricted, HA-1H T cell receptor (TCR) transduced patient-derived T cell (MDG1021) immunotherapy, with secondary endpoints including preliminary efficacy, in patients with relapsed or persistent hematologic malignancies after allogeneic hematopoietic stem cell transplantation. In the dose-escalation part of the study, at least 9 patients will be treated with MDG1021 at 3 different doses to assess the safety and the maximum tolerated dose using a standard 3+3 cohort design. Thereafter, the selected optimal MDG1021 dose will be assessed for safety and preliminary efficacy in 20 additional patients during the dose-expansion part of the study. Manufacturing feasibility will be determined. MDG1021 will be administered by single intravenous infusion.

HA-1H is exclusively expressed on cells of the hematopoietic system. If the patient's blood-cells, and thus lymphoma or leukemic cells, carry the immunogenic version of the HA-1H antigen on their surface and the donor stem cells do not, MDG1021 immunotherapy could eradicate the patient's cancer cells and allow the donor stem cells to repopulate the patient's blood forming system.

Conditions: Acute Myeloid Leukemia, Acute Lymphoid Leukemia, Myelodysplastic Syndromes, Myeloproliferative Disorders, Chronic Myeloid Leukemia, Myelofibrosis
Being tested: MDG1021 dose 1, MDG1021 dose 2, MDG1021 dose 3, MDG1021 optimal dose
Keywords: Allogeneic hematopoietic stem cell transplantation, Relapsed hematologic malignancy, Persistent hematologic malignancy
Medical subject headings: Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Myelodysplastic Syndromes, Myeloproliferative Disorders, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Primary Myelofibrosis, Multiple Myeloma, Lymphoma

What participants receive

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

MDG1021 dose 1Drug
3 patients to receive dose1: target dose of 0.3x10^6 HA-1H TCR transduced T cells/kg BW ±20% in 100 mL
MDG1021 dose 2Drug
3 patients to receive dose 2: target dose of 1x10^6 HA-1H TCR transduced T cells/kg BW ±20% in 100 mL
MDG1021 dose 3Drug
3 patients to receive dose 3: target dose of 3x10^6 HA-1H TCR transduced T cells/kg BW +20% in 100 mL
MDG1021 optimal doseDrug
20 patients to receive the selected optimal dose

Study groups in NCT04464889
Study group	Role	What they receive
MDG1021	Experimental	Dose-escalation part of the study to investigate 3 MDG1021 doses. Dose-expansion part of the study to investigate the selected optimal MDG1021 dose. Receives: Drug: MDG1021 dose 1; Drug: MDG1021 dose 2; Drug: MDG1021 dose 3; Drug: MDG1021 optimal dose

What is being measured

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

Safety and tolerability of HA-1H TCR transduced T cells: incidence and severity of adverse events
To assess the incidence and severity of adverse events during the dose escalation part of the study according to the NCI CTCAE v5.0
Measured: up to 28 days after T cell infusion
Maximum tolerated dose (MTD) of HA-1H TCR transduced T cells
To asses the maximum tolerated dose (MTD) of MDG1021 as determined by dose-limiting toxicities (DLTs)
Measured: up to 28 days after T cell infusion
Recommended phase 2 dose (RP2D) of HA-1H TCR transduced T cells
To asses the recommended phase II dose (RP2D) of MDG1021
Measured: up to 28 days after T cell infusion
Safety and tolerability of HA-1H TCR transduced T cells at recommended phase II dose: incidence and severity of adverse events
To assess the incidence and severity of adverse events of MDG1021 at the RP2D during the expansion part of the study according to the NCI CTCAE v5.0
Measured: up to 28 days after T cell infusion

Secondary outcomes (7)

Safety and tolerability (both parts of the study): incidence and severity of adverse events
To assess the incidence and severity of AEs ≥ grade 3 (NCI CTCAE v5.0)
Measured: Up to 12 months after T cell infusion
Overall response rate
To assess the overall response rate defined as the proportion of patients with a best overall response of complete response (CR), partial response (PR), and/or their disease specific subcategories
Measured: Up to 12 months after T cell infusion
Overall survival
To assess the overall survival (OS) defined as the time from the date of signing the informed consent until the documented date of death.
Measured: Up to 12 months afterT cell infusion
Progression free survival
To assess the progression-free survival (PFS) defined as the time from the date of signing the date of signed informed consent until progressive disease/relapse or death, whichever occurs first.
Measured: Up to 12 months afterT cell infusion
Duration of response
To assess the duration of response (DoR) defined as time from the date of the first documented response to the first documented progression of disease or death due to underlying cancer.
Measured: Up to 12 months afterT cell infusion
Quality of life (EQ-5D-5L)
The quality of life will be assessed by using the EQ-5D-5L questionnaire, consisting of 5 questions. Higher scores correspond to higher quality of life.
Measured: Up to 12 months afterT cell infusion
Quality of life (VAS)
The quality of life will be assessed by a visual analog scale (EuroQoL), having a range of 0 ot 100, with higher scores corresponding to better quality of life.
Measured: Up to 12 months afterT cell infusion

Timeline

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

2 Jul 2020Jul 2025

First posted9 Jul 2020
Study start2 Jul 2020
Primary completionJul 2023 (estimated)
Study completionJul 2025 (estimated)

Why it stopped: Medigene transfered all rights to a new Sponsor

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Acute Myeloid LeukemiaStudies 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
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Model description: The aim of the study is to determine the recommended phase II dose (RP2D) of MDG1021 that will be determined on the basis of safety and ability to manufacture a cohort specific MDG1021 dose. The dose-escalation part of the study is designed to assess the safety and the MTD of MDG1021, using a standard 3+3 cohort design, with up to 3 additional subjects to be enrolled in case of dose limiting toxicity (DLT). Upon completion of the dose-escalation part of the study, 20 eligible patients will be treated in the expansion part of the study with MDG1021 at the RP2D to further evaluate safety, feasibility and preliminary efficacy.
Masking: None (open label)
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04464889
Sponsor's protocol ID: CD-TCR-003
Status last verified: Sep 2021
First submitted: 1 Jul 2020
Last updated: 8 Oct 2021
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Acute Myeloid Leukemia trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Dose-Escalation, Open Label Phase I Study to Assess the Safety, Feasibility and Preliminary Efficacy of HA-1H TCR Modified T Cells, MDG1021, in Patients With Relapsed or Persistent Hematologic Malignancies After Allogeneic HSCT With or Without Unmanipulated DLI
ClinicalTrials.gov ID: NCT04464889
Acronym / sponsor ID: CD-TCR-003
Conditions: Acute Myeloid Leukemia, Acute Lymphoid Leukemia, Myelodysplastic Syndromes, Myeloproliferative Disorders, Chronic Myeloid Leukemia, Myelofibrosis
Keywords: Allogeneic hematopoietic stem cell transplantation, Relapsed hematologic malignancy, Persistent hematologic malignancy
Phase: Phase 1
Study type: Interventional
Recruitment status: WithdrawnReason stopped: Medigene transfered all rights to a new Sponsor
Enrolment: 0 participants (actual)
Lead sponsor: Medigene AGIndustry (pharma, biotech, devices)
Study start: 2 Jul 2020 (actual)
Primary completion: Jul 2023 (estimated)
Study completion: Jul 2025 (estimated)
First posted: 9 Jul 2020 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: The aim of the study is to determine the recommended phase II dose (RP2D) of MDG1021 that will be determined on the basis of safety and ability to manufacture a cohort specific MDG1021 dose. The dose-escalation part of the study is designed to assess the safety and the MTD of MDG1021, using a standard 3+3 cohort design, with up to 3 additional subjects to be enrolled in case of dose limiting toxicity (DLT). Upon completion of the dose-escalation part of the study, 20 eligible patients will be treated in the expansion part of the study with MDG1021 at the RP2D to further evaluate safety, feasibility and preliminary efficacy.

Arm	Type	Receives
MDG1021	Experimental	Drug: MDG1021 dose 1, Drug: MDG1021 dose 2, Drug: MDG1021 dose 3, Drug: MDG1021 optimal doseDose-escalation part of the study to investigate 3 MDG1021 doses. Dose-expansion part of the study to investigate the selected optimal MDG1021 dose.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

Relapsed or persistent disease is defined according to disease specific guidelines (AML, CML, MM, ALL, MDS, MPN, MF and malignant B- or T-cell lymphoma) and includes MRD positivity.
Patients positive for HLA-A*02:01 according to genotyping results
Patients positive for HA-1H
Patients who received the allo-HSCT at least 100 days preceding the leukapheresis
Patients (i.e. recipient) transplanted with a sibling or unrelated HSCT donor

Key exclusion criteria (22 listed)

Evidence of acute or chronic graft versus host disease (GVHD) ≥ grade II
Serologic evidence of acute or chronic hepatitis B virus infection (i.e. positive for HBsAg or IgM anti-HBc). Positive HIV and HCV serology or active bacterial infection
Medical or psychological conditions that would make the patient unsuitable candidate for cell therapy at the discretion of the investigator. Special risks to be considered:
Clinically significant and ongoing immune suppression including, but not limited to immunosuppressive agents (e.g. cyclosporine or corticosteroids (at an equivalent dose of ≥ 10 mg prednisone per day)). Inhaled steroid and physiological replacement for adrenal insufficiency is allowed
Patients with a history of primary immunodeficiency

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
MDG1021 dose 13 patients to receive dose1: target dose of 0.3x10^6 HA-1H TCR transduced T cells/kg BW ±20% in 100 mL	Drug	MDG1021
MDG1021 dose 23 patients to receive dose 2: target dose of 1x10^6 HA-1H TCR transduced T cells/kg BW ±20% in 100 mL	Drug	MDG1021
MDG1021 dose 33 patients to receive dose 3: target dose of 3x10^6 HA-1H TCR transduced T cells/kg BW +20% in 100 mL	Drug	MDG1021
MDG1021 optimal dose20 patients to receive the selected optimal dose	Drug	MDG1021

Primary outcome

Safety and tolerability of HA-1H TCR transduced T cells: incidence and severity of adverse events
Time frame: up to 28 days after T cell infusion
To assess the incidence and severity of adverse events during the dose escalation part of the study according to the NCI CTCAE v5.0
Maximum tolerated dose (MTD) of HA-1H TCR transduced T cells
Time frame: up to 28 days after T cell infusion
To asses the maximum tolerated dose (MTD) of MDG1021 as determined by dose-limiting toxicities (DLTs)
Recommended phase 2 dose (RP2D) of HA-1H TCR transduced T cells
Time frame: up to 28 days after T cell infusion
To asses the recommended phase II dose (RP2D) of MDG1021
Safety and tolerability of HA-1H TCR transduced T cells at recommended phase II dose: incidence and severity of adverse events
Time frame: up to 28 days after T cell infusion
To assess the incidence and severity of adverse events of MDG1021 at the RP2D during the expansion part of the study according to the NCI CTCAE v5.0

7 secondary outcomes

Safety and tolerability (both parts of the study): incidence and severity of adverse events
Time frame: Up to 12 months after T cell infusion
Overall response rate
Time frame: Up to 12 months after T cell infusion
Overall survival
Time frame: Up to 12 months afterT cell infusion
Progression free survival
Time frame: Up to 12 months afterT cell infusion
Duration of response
Time frame: Up to 12 months afterT cell infusion
Quality of life (EQ-5D-5L)
Time frame: Up to 12 months afterT cell infusion
Quality of life (VAS)
Time frame: Up to 12 months afterT cell infusion

Results and safety

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

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2021.
Individual participant dataSharing planned: No

Related trials for Acute Myeloid Leukemia

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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.

Peter van Balen, MD principal investigator

Leiden University Medical Centre

Rene Goedkoop, MD study director

Medigene AG

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MDG1021 dose 1, MDG1021 dose 2 and MDG1021 dose 3 in people with Acute Myeloid Leukemia and Acute Lymphoid Leukemia, run by Medigene AG at 1 site in Netherlands.

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 12 inclusion and 22 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 8 Oct 2021. 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 Netherlands. 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?

Safety and tolerability of HA-1H TCR transduced T cells: incidence and severity of adverse events (time frame: up to 28 days after T cell infusion). The study lists 4 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 NCT04464889.

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 8 Oct 2021.