Hu8F4 for Blood Cancers

Recruiting at 3 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

72 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of anti-PR1/HLA-A2 monoclonal antibody Hu8F4 (Hu8F4) in treating patients with malignancies related to the blood (hematologic). Monoclonal antibodies, such as Hu8F4, may interfere with the ability of cancer cells to grow and spread.

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.

What data supports the effectiveness of the drug Hu8F4 for blood cancers?

Research shows that hydroxyurea, a component of Hu8F4, has been effective in reducing high white blood cell counts in certain types of leukemia and can kill specific leukemia cells that are resistant to other treatments. This suggests that Hu8F4 might also be effective in treating blood cancers. ^{1 2 3 4 5}

What makes the drug Hu8F4 unique for treating blood cancers?

Hu8F4 is unique because it involves hydroxyurea (HU), which has been shown to target specific cancer cells through mechanisms like necroptosis and iron chelation, offering a novel approach for treating resistant forms of leukemia by affecting genes like MMP2 and inducing fetal hemoglobin production. ^{1 2 3 6 7}

Research Team

Tapan Kadia, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

CDK4/CDK6 inhibition as a novel strategy to suppress the growth and survival of BCR-ABL1T315I+ clones in TKI-resistant CML. [2022]

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

Targeting matrix metallopeptidase 2 by hydroxyurea selectively kills acute myeloid mixed-lineage leukemia. [2022]

3. Australia pubmed.ncbi.nlm.nih.gov

Extreme leucocytosis and prognosis of newly diagnosed patients with acute non-lymphocytic leukaemia. [2021]

4. Thailand pubmed.ncbi.nlm.nih.gov

Longer Hydroxyurea Administration Prior to Imatinib Mesylate is Risk Factor for Unsuccessful Major Molecular Response in Chronic-Phase Chronic Myeloid Leukemia: Possibility of P-Glycoprotein Role. [2021]

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

Cellular pharmacodynamics and plasma pharmacokinetics of parenterally infused hydroxyurea during a phase I clinical trial in chronic myelogenous leukemia. [2017]

6. Italy pubmed.ncbi.nlm.nih.gov

Response to hydroxyurea treatment in Iranian transfusion-dependent beta-thalassemia patients. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Treatment with Hydroxyurea Leads to Fetal Hemoglobin Reactivation through CA1 and LIN28B Genes: An In&#160;Vitro Study. [2022]