NEXI-001 + Decitabine for AML or MDS

Overseen By Monzr M. Al Malki, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: GVHD, Cardiovascular disease, Autoimmune, others

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

Compensation: Varies

Number of Visits: 4

Duration: 33-38 days per cycle

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) that has returned or not responded after a bone marrow transplant. The treatment combines NEXI-001 (a therapy where immune cells are modified to attack cancer), decitabine (a drug that helps create normal blood cells and kills abnormal ones), and chemotherapy. The trial aims to determine the safest dose and identify any side effects. Eligible participants have AML or MDS that returned or didn't respond after a matched donor bone marrow transplant. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that patients receiving systemic corticosteroids or other immunosuppressant agents at the time of initiation of chemotherapy are excluded, so you may need 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 shows that NEXI-001, a type of T cell therapy, has been tested for safety and tolerability. Early results from other studies indicate that patients with AML (Acute Myeloid Leukemia) or MDS (Myelodysplastic Syndromes) generally tolerate this treatment well. Some patients have experienced mild to moderate side effects, while serious side effects remain rare.

Research has found decitabine to be relatively safe for treating AML and MDS. It helps produce normal blood cells and targets abnormal ones. Although some patients may experience low blood cell counts, it is generally considered effective with manageable side effects.

These findings suggest that combining NEXI-001 and decitabine could be safe for those considering this trial, but individual experiences may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about NEXI-001 for treating acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) because it offers a novel approach compared to standard chemotherapy and hypomethylating agents like azacitidine and decitabine alone. NEXI-001 utilizes a unique mechanism by harnessing the power of T cells to specifically target and attack cancer cells, which could lead to improved outcomes. Additionally, its combination with decitabine and lymphodepletion chemotherapy may enhance its effectiveness by creating an optimal environment for the T cells to function. This innovative strategy has the potential to provide a more targeted treatment with fewer side effects than traditional therapies.

What evidence suggests that NEXI-001 combined with decitabine and chemotherapy might be an effective treatment for AML or MDS?

In this trial, participants will receive a combination of NEXI-001, an advanced cell therapy, and Decitabine. Studies suggest that NEXI-001 holds promise for treating acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Early results indicate that these specially designed cells can enhance the immune system's ability to attack cancer cells, particularly in patients whose cancer has returned or who do not respond to treatment after a stem cell transplant. Decitabine, used alongside NEXI-001 in this trial, has proven effective and safe for treating AML and MDS. It helps produce normal blood cells while targeting abnormal ones. The combination aims to prepare and support the body in fighting these blood cancers. ^{1 2 4 6 7}

Who Is on the Research Team?

Monzr M. Al Malki

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) that has returned after treatment or hasn't responded to previous treatments, and who have had a matched donor stem cell transplant. Specific eligibility details are not provided.

Inclusion Criteria

I am mostly able to care for myself and carry out daily activities.

I had a stem cell transplant from a donor over 100 days ago.

Documented informed consent of the participant and/or legally authorized representative and documented informed consent of the donor

Exclusion Criteria

The donor I have has an ongoing infection that isn't getting better with treatment.

Known hypersensitivity to any component of the NEXI-001 T-cell product or specific medications

I have not received a live virus vaccine in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients receive decitabine and lymphodepleting chemotherapy followed by NEXI-001 T cell infusions

33-38 days per cycle

Multiple visits for infusions and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

Every 3 months

Extension

Patients may receive an additional cycle of treatment if criteria are met

33-38 days per additional cycle

What Are the Treatments Tested in This Trial?

Interventions

• Decitabine
• Fludarabine and Cyclophosphamide
• NEXI-001

Trial Overview The trial tests the safety and optimal dose of NEXI-001, a CAR T-cell therapy, combined with decitabine and lymphodepleting chemotherapy using fludarabine and cyclophosphamide in patients with relapsed/refractory AML or MDS post-transplant.

How Is the Trial Designed?

Group I: Treatment (NEXI-001, decitabine, chemotherapy) Experimental Treatment 12 Interventions

DONOR: Donors undergo leukapheresis on study. PATIENTS: Patients may receive bridging therapy per standard of care ≥ 14 days prior to the start of cycle 1. Patients receive decitabine IV over 1 hour QD on day -3, -5 or -10 to day -1, lymphodepletion chemotherapy with fludarabine IV over 30 minutes QD and cyclophosphamide IV over 60 minutes QD on day -5 to -3 and then receive NEXI-001 IV over 30 minutes QD on days 1, 8 and 15 of cycle 1. Cycles repeat every 33 or 38 days in the absence of disease progression or unacceptable toxicity. If NEXI-001 cells remain and treatment criteria are met, patients may receive and additional cycle of decitabine IV over 1 hour QD on day -5 to -1 and NEXI-001 IV QD on days 1, 8 and 15 in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening, bone marrow aspirate and/or bone marrow biopsy, PET/ CT scan or MRI and blood sample collection throughout the study.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Decitabine is an effective hypomethylating agent for treating acute myeloid leukemia (AML), significantly improving overall survival and response rates compared to standard care, based on results from the phase 3 DACO-016 trial with adult patients who are not eligible for standard chemotherapy.

The treatment is generally well tolerated and remains effective even in patients with adverse-risk karyotypes or TP53 mutations, making it a valuable option for those unfit for more intensive therapies, with potential for future combination treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Clinical Value of Decitabine Monotherapy in Patients with Acute Myeloid Leukemia. Santini, V., Lübbert, M., Wierzbowska, A., et al.[2022]

Decitabine, a hypomethylating agent, has been shown to improve outcomes in patients with myelodysplastic syndromes (MDS), achieving a 17% overall response rate and 9% complete remissions in a Phase III trial compared to best supportive care.

In high-risk MDS patients, decitabine significantly prolonged the time to transformation to acute myelogenous leukemia or death, indicating its potential to alter the disease's natural history.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of decitabine in the treatment of myelodysplastic syndromes. Atallah, E., Kantarjian, H., Garcia-Manero, G.[2019]

In a study of 79 patients with acute myeloid leukemia and myelodysplastic syndromes, decitabine alone or in combination with CAG chemotherapy showed high overall response rates (ORR) of 53.3% to 69.2%, indicating its efficacy in treating these conditions.

All treatment groups tolerated decitabine well, with no treatment-related deaths reported, although there were significant adverse events such as infections and hematological toxicities, which were managed with supportive care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The clinical efficacy of the patients of acute myeloid leukemia and myelodysplastic syndromes treated with decitabine alone, combined with half or one couse of CAG regimen]. Gao, S., Qiu, H., Jin, Z., et al.[2018]

This case study reports the successful use of decitabine and lenalidomide in treating a patient with myelodysplastic syndrome (MDS) characterized by a 5q deletion and elevated blast counts, leading to significant improvements in hemoglobin levels and cessation of transfusion dependency after just two cycles.

The treatment combination was well-tolerated with no notable side effects, suggesting it could be a promising option for MDS patients with similar profiles, although further validation in larger studies is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide Plus Decitabine Treatment in a Myelodysplastic Syndrome Patient With Deletion 5q and Excess Blasts. Serin, I., Eren, R., Dogu, MH.[2020]

In a phase I/II study involving 37 patients with myelodysplastic syndrome (MDS), decitabine was found to be safe, with manageable side effects, and showed efficacy with a complete response rate of 20.6% at a dosage of 20 mg/m².

The treatment led to significant hypomethylation in myeloid cells, which may contribute to its therapeutic effects, and resulted in a median duration of remission of over 474 days, with a 2-year acute myeloid leukemia-free survival rate of 52%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II study of decitabine in patients with myelodysplastic syndrome: a multi-center study in Japan. Oki, Y., Kondo, Y., Yamamoto, K., et al.[2021]

In a study of 44 patients with relapsed/refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS), the combination of decitabine with the EIAG regimen resulted in a higher modified composite complete response (mCRc) rate of 72.7% compared to 40.9% in the CAG regimen group, indicating improved efficacy.

Both treatment regimens led to significant myelosuppression as a common adverse effect, but there was no increase in non-hematological toxicities, suggesting that decitabine combined with EIAG is a safe option that enhances remission rates without adding extra risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and Safety of Decitabine Combined with Modified EIAG Regimen in the Treatment of Patients with Relapsed/Refractory Acute Myeloid Leukemia and High-risk Myelodysplastic Syndrome]. Mao, JP., Xue, LG., Zhu, YX., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31939424/

Decitabine: An effective and safe treatment for ... Conclusions: Our data demonstrated that decitabine was effective and relatively safe in treating MDS and AML. Patients with agranulocytosis and severe anemia ...

2. ashpublications.org ashpublications.org/bloodneoplasia/article/2/2/100071/535264/A-phase-2-study-of-decitabine-with-or-without

A phase 2 study of decitabine with or without carboplatin and ... Key PointsDAC/ATO was more clinically effective against MDS/AML than DAC/Carbo, absent adverse toxicity.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0145212621000254

Efficacy of 10-day decitabine in acute myeloid leukemia Highlights · Real world outcomes using the 10 day decitabine regimen in AML are lacking. · 10-day decitabine had an ORR of 36.1% in AML in the upfront setting.

4. journals.lww.com journals.lww.com/cancerjournal/fulltext/2019/15070/decitabine__an_effective_and_safe_treatment_for.6.aspx

Decitabine: An effective and safe treatment for... Conclusions: Our data demonstrated that decitabine was effective and relatively safe in treating MDS and AML. Patients with agranulocytosis and severe anemia ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01786343

NCT01786343 | Decitabine for Older or Unfit Patients With ... The goal of this clinical research study is to compare how well 2 different dosing schedules of decitabine may help control AML. Decitabine is designed to ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2950328025000068

A phase 2 study of decitabine with or without carboplatin ... In addition, we observed a prolonged median OS among patients with MDS who received DAC/ATO (16.5 months), compared to those who received DAC/Carbo (4.6 months) ...

7. hematologyadvisor.com hematologyadvisor.com/news/acute-myeloid-leukemia-aml-decitabine-regimen-less-toxic-chemotherapy/

10-Day Decitabine Regimen May Be Less Toxic Than ... Analysis showed, at this point, that the 4-year overall survival rate was 26% in the decitabine group vs 30% in the control group (hazard ratio ...