Hu8F4 for Blood Cancers

Not currently recruiting at 4 trial locations

Overseen By Tapan M Kadia

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Systemic steroids

Disqualifiers: Uncontrolled infection, Active heart disease, CNS disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days per cycle

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the safety and optimal dosage of a new treatment called Hu8F4 for certain blood cancers. Hu8F4, a monoclonal antibody, may help stop cancer cells from growing and spreading. It targets patients with specific blood cancers like acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS) who have not responded to other treatments. Participants should have a specific blood marker called HLA-A2 and have relapsed or treatment-resistant disease. As a Phase 1 trial, the research focuses on understanding how the treatment 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 protocol does not specify if you need to stop taking your current medications, but you must be at least 2 weeks from prior chemotherapy, radiation therapy, or major surgery, and at least 4 weeks or 5 half-lives from other investigational anticancer therapy. Hydroxyurea does not require a washout period before starting the study drug.

Is there any evidence suggesting that Hu8F4 is likely to be safe for humans?

Research shows that the monoclonal antibody Hu8F4 is undergoing safety testing for blood cancers. In earlier studies, patients received Hu8F4 through an IV while researchers monitored for side effects. The initial focus ensured the treatment's safety for individuals with blood cancers.

Since this marks the first human testing of Hu8F4, the primary goal is to determine a safe dose and identify any adverse reactions. Although detailed safety data from earlier studies isn't available, the trial's existence indicates Hu8F4 has shown enough promise for human testing. Participants receive close monitoring for side effects, and the treatment continues only if deemed safe.

Doctors ensure participant safety and will halt the treatment if serious concerns arise. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for blood cancers involve chemotherapy, radiation, or targeted therapies like tyrosine kinase inhibitors. But Hu8F4 works differently, targeting a specific protein complex called PR1/HLA-A2 with its monoclonal antibody component. This precise targeting could mean fewer side effects, as it aims to attack cancer cells more directly without harming normal cells. Researchers are excited because this approach might offer a new way to treat blood cancers, potentially improving outcomes for patients who don't respond well to existing therapies.

What evidence suggests that Hu8F4 might be an effective treatment for blood cancers?

Research has shown that Hu8F4, a specially designed antibody, holds promise for treating blood cancers. Studies have found that Hu8F4 targets a specific protein on cancer cells, making it effective against diseases like acute myeloid leukemia (AML), even when chemotherapy fails. Early results suggest it can slow the growth and spread of these cancer cells. This antibody attaches to a unique part of the cancer cells, potentially helping the immune system to identify and attack the cancer more effectively. Although more research is needed, these early findings are encouraging for its potential use in blood cancer treatment. Participants in this trial will receive Hu8F4 to further evaluate its effectiveness and safety. ^{2 6 7 8 9}

Who Is on the Research Team?

Tapan Kadia, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced blood-related cancers like certain types of leukemia, myelodysplastic syndrome, or myelofibrosis. Participants must have specific genetic traits (HLA-A2), failed previous treatments, and be in good enough health to tolerate the study drug. Pregnant women are excluded and contraception is required during the trial.

Inclusion Criteria

Chronic myelomonocytic leukemia (CMML)

Patients with any of the following diagnoses are eligible: high-risk MDS (i.e. refractory anemia with excess blasts [RAEB-1 or RAEB-2] by World Health Organization [WHO] classification, or any WHO subset with International Prognostic Scoring System [IPSS] intermediate-2 or high, or any patients that have failed prior therapy with hypomethylating agents)

Total bilirubin =< 1.5 x the upper limit of normal unless considered due to Gilbert's syndrome or leukemic involvement

Exclusion Criteria

You are not currently receiving any other treatments for your blood cancer, except for supportive care.

Patients who have had any major surgical procedure within 14 days of day 1

Patients with known central nervous system infiltration with leukemia

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive anti-PR1/HLA-A2 monoclonal antibody Hu8F4 intravenously over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for overall survival, disease-free survival, and event-free survival

Up to 4 years

What Are the Treatments Tested in This Trial?

Interventions

• Hu8F4

Trial Overview The trial tests Hu8F4, a monoclonal antibody that may block cancer growth. It's in phase I to determine safe dosage levels and side effects. Patients will undergo lab biomarker analysis and pharmacological studies to see how well Hu8F4 works against their cancer.

How Is the Trial Designed?

Group I: Treatment (Hu8F4) Experimental Treatment 3 Interventions

Patients receive anti-PR1/HLA-A2 monoclonal antibody Hu8F4 IV over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. aacrjournals.org aacrjournals.org/cancerres/article/83/8_Supplement/CT101/725359/Abstract-CT101-Phase-I-study-of-the-T-cell

Abstract CT101: Phase I study of the T-cell receptor-like ... Hu8F4 is a humanized T-cell receptor-like monoclonal antibody that binds to the conformational epitope of PR1 bound to HLA-A2, which is highly, differentially ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4935597/

Activity of 8F4, a T cell receptor-like anti-PR1/HLA-A2 antibody ... Our data provide evidence that 8F4 antibody is highly active in AML, including chemotherapy-resistant disease, supporting its potential use as a therapeutic ...

3. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT02530034/

Clinical Trial: NCT02530034 To measure the overall survival, disease-free survival and event-free survival of patients with leukemias or MDS treated with Hu8F4. OUTLINE: ...

4. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/1545/503273/Phase-I-Study-of-the-T-Cell-Receptor-like-Antibody

Phase I Study of the T-Cell Receptor-like Antibody, Hu8F4 in ... Phase I study of the T-cell receptor-like antibody, Hu8F4 in patients with relapsed and refractory myeloid malignancies.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1465324924007692

Hu8F4-CAR T cells with mutated Fc spacer segment ... We have demonstrated high efficacy of Hu8F4-CAR-T cells against PR1/HLA-A2-expressing cell lines and leukemic blasts from patients with acute myeloid leukemia ...

6. clinicaltrial.be clinicaltrial.be/en/details/73935?active_not_recruiting=1&completed=0&enrolling_by_invitation=1&only_active=0&only_eligible=0&only_recruiting=0&per_page=20

Hu8F4 in Treating Patients With Advanced Hematologic Mali... Patients receive anti-PR1/HLA-A2 monoclonal antibody Hu8F4 intravenously (IV) over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of ...

7. trials-api.montefioreeinstein.org trials-api.montefioreeinstein.org/node/264626

Hu8F4 in Treating Patients With Advanced Hematologic ... Safety data will be summarized using frequency and percentage for all patients. Outcome Measure. Minimum safety data. Outcome Time Frame. 4 weeks. Outcome ...

8. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/anti-pr1-hla-a2-monoclonal-antibody-hu8f4

Definition of anti-PR1/HLA-A2 monoclonal antibody Hu8F4 Upon administration, anti-PR1/HLA-A2 monoclonal antibody Hu8F4 selectively binds to a combined epitope of the PR1/HLA-A2 complex expressed on acute myeloid ...

9. mycancergenome.org mycancergenome.org/content/drugs/anti-pr1-hla-a2-monoclonal-antibody-hu8f4/

anti-pr1/hla-a2 monoclonal antibody hu8f4 Upon administration, anti-PR1/HLA-A2 monoclonal antibody Hu8F4 selectively binds to a combined epitope of the PR1/HLA-A2 complex expressed on acute myeloid ...