CYAD-02 for Leukemia/Preleukemia

(CYCLE-1 Trial)

Recruiting in Palo Alto (17 mi)

+4 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Celyad Oncology SA

Must not be taking: Anticoagulants

Disqualifiers: CNS tumor, Active infections, others

No Placebo Group

Trial Summary

What is the purpose of this 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. Patients receive mild chemotherapy first, followed by CYAD-02 infusions to target cancer cells. If effective, they may receive additional doses.

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.

What makes the treatment CYAD-02 unique for leukemia/preleukemia?

CYAD-02 is a novel treatment that involves genetically modified cells designed to target and destroy cancer cells, which is different from traditional chemotherapy or radiation that broadly attacks rapidly dividing cells. This approach may offer a more targeted and potentially less toxic option for patients with leukemia or preleukemia. ^{1 2 3 4 5}

Research Team

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• CYAD-02 (CAR T-cell Therapy)
• ENDOXAN (Alkylating agents)
• Fludara (Alkylating agents)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Recognition of preleukemia. [2004]

2. United States pubmed.ncbi.nlm.nih.gov

Human preleukemia. [2019]

3. Italy pubmed.ncbi.nlm.nih.gov

Secondary leukaemias. Clinical and cytobiological aspects. [2005]

4. France 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)]. [2006]

5. China pubmed.ncbi.nlm.nih.gov

Clinical and laboratory features of preleukemia patients. [2006]