CYAD-02 for Leukemia/Preleukemia

(CYCLE-1 Trial)

Recruiting at 4 trial locations

Overseen By Frederic LEHMANN, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Celyad Oncology SA

Must not be taking: Anticoagulants

Disqualifiers: CNS tumor, Active infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

Duration: 3 weeks

27 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CYAD-02, a type of cell therapy, for certain blood cancers, specifically acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The goal is to determine the right dose and assess the treatment's effectiveness when combined with a specific chemotherapy. People with AML or MDS that hasn't responded to previous treatments and who can't undergo standard therapy might be suitable for this trial. Participants will first receive chemotherapy to prepare their bodies, followed by CYAD-02 infusions at different dose levels to identify the most effective one. As a Phase 1 trial, this research aims to understand how CYAD-02 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those who are receiving certain cancer therapies or blood thinners like warfarin, heparin, or direct oral anticoagulants. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that CYAD-02 is generally safe. In earlier studies, patients tolerated the treatment well, and no serious side effects were linked to the dose. However, some significant reactions occurred. One patient had a severe reaction during the infusion, and another experienced a moderate case of cytokine release syndrome (CRS), a common immune response. These findings suggest that while CYAD-02 is mostly safe, some patients might have strong reactions.

Overall, CYAD-02 is considered safe for ongoing trials, but participants should be aware of these possible reactions. Those considering joining a trial should consult a healthcare provider to better understand the risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for leukemia?

Researchers are excited about CYAD-02 for leukemia and preleukemia because it offers a novel approach compared to standard treatments like chemotherapy and targeted therapies. Unlike these traditional treatments, CYAD-02 is a CAR-T cell therapy, which means it involves modifying a patient's own immune cells to specifically target and attack cancer cells. This personalized approach could lead to more effective outcomes with potentially fewer side effects, as it directly harnesses the body's immune system against the cancer. Additionally, the dose escalation strategy in the trial allows researchers to fine-tune the treatment's safety and effectiveness, further enhancing the potential for successful outcomes.

What evidence suggests that CYAD-02 might be an effective treatment for leukemia/preleukemia?

Research has shown that CYAD-02, which participants in this trial will receive, holds promise for treating leukemia and preleukemia. Studies have found that CYAD-02, a type of CAR-T cell therapy using modified immune cells, effectively targets cancer cells. Early results suggest it may benefit patients who haven't responded to standard treatments. CYAD-02 targets specific proteins on leukemia cells, potentially aiding the immune system in attacking the cancer. While more research is needed, these initial findings are encouraging for those with relapsed or difficult-to-treat acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for patients with relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who can't have standard treatments. They must have had prior therapy, adequate liver and kidney function, a decent heart pump function, and acceptable lung capacity. Those with high blast counts in blood or central nervous system tumor history are excluded.

Inclusion Criteria

I have a type of blood cancer that has come back or didn’t respond to treatment, and I can't receive standard care.

My blood cancer can be measured for treatment response, and my blast cell count is below 15,000/L.

The patient must have a left ventricular ejection fraction of ≥ 40 %, as determined by echocardiography or a multigated acquisition scan.

Exclusion Criteria

I have a serious blood clotting disorder or am on blood thinners.

Patients with any positive serology test results at baseline

My cancer has spread to my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preconditioning Chemotherapy

Participants receive non-myeloablative preconditioning chemotherapy with cyclophosphamide and fludarabine for 3 consecutive days

1 week

3 visits (in-person)

Treatment

Participants receive CYAD-02 infusion following preconditioning chemotherapy

3 weeks

1 visit (in-person) per infusion

Consolidation Cycle

Non-progressive patients receive 3 additional CYAD-02 infusions at a 2-week interval without prior preconditioning

6 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 years

What Are the Treatments Tested in This Trial?

Interventions

• CYAD-02
• ENDOXAN
• Fludara

Trial Overview The study tests the safety and optimal dose of CYAD-02 after preconditioning chemotherapy with ENDOXAN and Fludara in AML/MDS patients. It's an early-phase trial aiming to enroll up to 27 participants without dose-limiting toxicities.

How Is the Trial Designed?

Group I: Dose Escalation Dose Level 3 Experimental Treatment 3 Interventions

in case of no dose limiting toxicity (DLT) and no replacement of patients,3 consecutive patients at the dose of 1x10e9 of CYAD-02 per infusion post preconditioning non-myeloablative chemotherapy according to a 3+3 study design. The preconditioning therapy consists of 3 consecutive days of cyclophosphamide (300 mg/m²/day) and fludarabine (30 mg/m²/day), two days before the CYAD-02 infusion. In case of no progression at D22, the patient is eligible to receive a consolidation cycle of 3 additional CYAD-02 infusion at the same dose level, without prior preconditioning chemotherapy.

Group II: Dose Escalation Dose Level 2 Experimental Treatment 3 Interventions

in case of no dose limiting toxicity (DLT) and no replacement of patients,3 consecutive patients at the dose of 3x10e8 of CYAD-02 per infusion post preconditioning non-myeloablative chemotherapy according to a 3+3 study design. The preconditioning therapy consists of 3 consecutive days of cyclophosphamide (300 mg/m²/day) and fludarabine (30 mg/m²/day), two days before the CYAD-02 infusion. In case of no progression at D22, the patient is eligible to receive a consolidation cycle of 3 additional CYAD-02 infusion at the same dose level, without prior preconditioning chemotherapy.

Group III: Dose Escalation Dose Level 1 Experimental Treatment 3 Interventions

in case of no dose limiting toxicity (DLT) and no replacement of patients, 3 consecutive patients at the dose of 1x10e8 of CYAD-02 per infusion post preconditioning non-myeloablative chemotherapy according to a 3+3 study design. The preconditioning therapy consists of 3 consecutive days of cyclophosphamide (300 mg/m²/day) and fludarabine (30 mg/m²/day), two days before the CYAD-02 infusion. In case of no progression at D22, the patient is eligible to receive a consolidation cycle of 3 additional CYAD-02 infusion at the same dose level, without prior preconditioning chemotherapy.

Who Is Running the Clinical Trial?

Celyad Oncology SA

Lead Sponsor

Trials

13

Recruited

1,300+

Published Research Related to This Trial

Preleukemia is a condition that can only be diagnosed retrospectively, and it shows various clinical signs that help in recognizing its pattern, indicating it as an early form of neoplastic disease that can progress to acute leukemia.

Advancements in cytogenetic and marrow culture studies have improved diagnostic criteria and prognostic indicators for preleukemia, but the term 'hemopoietic dysplasia' is recommended for prospective evaluations due to the lack of predictive criteria for individual outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recognition of preleukemia. Shively, JA.[2004]

Patients undergoing radiation and cytotoxic treatments for cancer are at a higher risk of developing secondary leukemia, particularly acute myeloblastic leukemia, due to specific preleukemic changes.

The study identifies key morphological and cytobiological features of the preleukemic phase, including myelodysplastic alterations and cytogenetic abnormalities, which differ from primary myelodysplastic states by showing hypocellularity and involvement of multiple cell lines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Secondary leukaemias. Clinical and cytobiological aspects. Quaglino, D., Di Leonardo, G., Ginaldi, L., et al.[2005]

In a review of 102 cases of preleukemic states and acute secondary leukemia (ASL) following chemotherapy or radiotherapy, 91% of the cases showed abnormal karyotypes, indicating a strong link between cytogenetic abnormalities and the development of ASL.

The study found that hypodiploidy, particularly involving chromosome 5 and/or chromosome 7, was common in these cases, and the presence of these abnormalities in preleukemia states suggests that cytogenetic analysis can be crucial for early detection and understanding of ASL, which has a poor prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cytogenetic study of preleukemic phases and of acute leukemia secondary to chemo-and/or radiotherapy. Review of the literature (102 cases)]. Smadja, N., Krulik, M., Debray, J.[2006]

The study identified eight significant clinical and laboratory features that differentiate preleukemia from chronic aplastic anemia (CAA) and atypical paroxysmal nocturnal hemoglobinuria (a-PNH), including specific cell types and genetic markers.

All patients with preleukemia met at least one of two proposed diagnostic criteria based on these features, indicating that these criteria could be effective for the prospective diagnosis of preleukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and laboratory features of preleukemia patients. Shi, J., Shao, Z., Chen, G., et al.[2006]

Preleukemia is an early phase of acute myelogenous leukemia (AML) characterized by hematopoietic dysfunction and symptoms like pancytopenia, indicating a significant reduction in blood cell types.

During preleukemia, the bone marrow shows hypercellularity and abnormal maturation of blood cell precursors, suggesting that the neoplastic clone is already established and may progress to full-blown AML if not addressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human preleukemia. Koeffler, HP., Golde, DW.[2019]

Citations

1. celyad.com celyad.com/wp-content/uploads/2020/11/Celyad-Oncology_ASH2020_poster990_CYAD02.pdf

First Results from the Dose Escalation Segment of the ... Key secondary endpoints include additional safety parameters, CYAD-02 cell kinetics, objective responses and duration of responses. CONCLUSIONS. ○ Preliminary ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04167696?term=AREA%5BBasicSearch%5D(AREA%5BInterventionSearch%5D(SENDOXAN)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL))&rank=10

Study in Relapsed/Refractory Acute Myeloid Leukemia or ... The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.

3. kucancercenter.org kucancercenter.org/cancer-clinical-trials/find-trial/clinical-trial-results/nct04167696

Participate in this Clinical Trial CYAD-02 NKG2D CAR-T Clinical dEvelopment. Brief Summary. Brief Summary. Type: Leukemias. Study Type: Treatment. Phase: I. ClinicalTrials.gov Identifier:

4. withpower.com withpower.com/trial/phase-1-leukemia-myeloid-10-2019-84bb6

CYAD-02 for Leukemia/Preleukemia (CYCLE-1 Trial) This trial tests CYAD-02, a cell-based treatment, in patients with relapsed or refractory AML or MDS who haven't responded to standard treatments.

5. ashpublications.org ashpublications.org/blood/article/134/Supplement_1/3931/424094/Next-Generation-NKG2D-based-CAR-T-cells-CYAD-02-Co

Next Generation NKG2D-based CAR T-cells (CYAD-02) Data from preclinical models have shown that CYAD-01 cells specifically target solid and hematological tumors. Encouraging preliminary results ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118702267

613.Acute Myeloid Leukemia: Clinical Studies First Results ... To date, the results demonstrate the safety and tolerability for CYAD-02 in patients with r/r AML and MDS with no dose-limiting toxicity ...

7. clin.larvol.com clin.larvol.com/trial-detail/NCT03018405

A Dose Escalation Phase I Study to Assess the Safety and ... A NKG2D-based CAR-T therapy in a multinational phase I dose escalation and expansion study targeting multiple solid and hematologic tumor types.

8. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04167696/

Clinical Trial: NCT04167696 Study in Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome Patients to Determine the Recommended Dose of CYAD-02 ... My ...