Clinical Trials /

Hu8F4 in Treating Patients With Advanced Hematologic Malignancies

NCT02530034

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
  • Chronic Myeloid Leukemia
  • Chronic Myelomonocytic Leukemia
  • Myelodysplastic Syndrome with Excess Blasts-1
  • Myelodysplastic Syndrome with Excess Blasts-2
  • Myelodysplastic Syndromes
  • Myelofibrosis
  • Refractory Anemia with Excess Blasts
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Hu8F4 in Treating Patients With Advanced Hematologic Malignancies
  • Official Title: Phase I Study of Hu8F4 in Patients With Advanced Hematologic Malignancies

Clinical Trial IDs

  • ORG STUDY ID: 2014-0057
  • SECONDARY ID: NCI-2015-02131
  • SECONDARY ID: P-TRP-2447-14
  • SECONDARY ID: 2014-0057
  • SECONDARY ID: P30CA016672
  • SECONDARY ID: P50CA100632
  • NCT ID: NCT02530034

Conditions

  • Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
  • Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Hematopoietic and Lymphoid Cell Neoplasm
  • High Risk Myelodysplastic Syndrome
  • Myelodysplastic Syndrome With Excess Blasts-1
  • Myelodysplastic Syndrome With Excess Blasts-2
  • Myelofibrosis
  • Recurrent Acute Myeloid Leukemia
  • Recurrent Chronic Myelomonocytic Leukemia
  • Refractory Chronic Myelomonocytic Leukemia
  • Secondary Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
Anti-PR1/HLA-A2 Monoclonal Antibody Hu8F4Hu8F4Treatment (Hu8F4)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the dose limiting toxicity (DLT) and minimum safe and biologically-effective
      dose of Hu8F4 when administered intravenously in patients with leukemia or myelodysplastic
      syndrome (MDS).

      II. To determine the pharmacokinetics (PK) of Hu8F4 following study drug administration.

      SECONDARY OBJECTIVES:

      I. To observe the anti-leukemia effects of Hu8F4 in patients with leukemias and MDS.

      II. To measure the overall survival, disease-free survival and event-free survival of
      patients with leukemias or MDS treated with Hu8F4.

      OUTLINE: This is a dose-escalation study.

      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 disease progression or
      unacceptable toxicity.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (Hu8F4)ExperimentalPatients 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.
  • Anti-PR1/HLA-A2 Monoclonal Antibody Hu8F4

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with any of the following diagnoses are eligible: 1) 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); 2) chronic myelomonocytic leukemia (CMML); 3) acute myeloid
             leukemia (AML) by WHO classification; 4) chronic myeloid leukemia in blast phase
             (CML-BP); 5) myelofibrosis with high-risk features (e.g., accelerated phase disease
             -10-19% blasts in peripheral blood or bone marrow-, or with Dynamic International
             Prognostic Scoring System [DIPSS]-plus high risk score)

          -  Patients must have relapsed/refractory disease and have failed, or are not candidates
             for, or have declined all available therapies of proven efficacy; they should also not
             be eligible for at the time of enrollment or have declined hematopoietic stem cell
             transplantation

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

          -  The effects of Hu8F4 on a fetus or nursing child are unknown; women of child-bearing
             potential (i.e., women who are pre-menopausal or not surgically sterile) must use
             acceptable contraceptive methods (abstinence, intrauterine device [IUD], oral
             contraceptive or double barrier device), and must have a negative urine pregnancy test
             within 2 weeks prior to beginning treatment on this trial; nursing patients are
             excluded; sexually active men must also use acceptable contraceptive methods for the
             duration of time on study

          -  Patients must have human leukocyte antigen (HLA)-A2 phenotype

          -  Must be able and willing to give written informed consent

          -  Patients 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, and have recovered from prior toxicities at least to grade 1; the exception
             is hydroxyurea that requires no washout prior to the start of study drug

          -  Clinically significant toxicities from prior chemotherapy must not be greater than
             grade 1

          -  Clearance creatinine or glomerular filtration rate (GFR) >= 40 mL/min

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

          -  Alanine aminotransferase (ALT) =< 3 x the upper limit of normal unless considered due
             to leukemic involvement

        Exclusion Criteria:

          -  Uncontrolled intercurrent illness including, but not limited to uncontrolled infection
             (patients must have no temperature >= 38.3 degrees Celsius [C] due to infection for at
             least 48 hrs to consider an infection controlled), psychiatric illness that would
             limit compliance with study requirements, or active heart disease including confirmed
             myocardial infarction within previous 3 months, symptomatic coronary artery disease,
             clinically significant arrhythmias not controlled by medication, or uncontrolled
             congestive heart failure New York (NY) Heart Association class III or IV

          -  Patients with current active malignancies or any remission for < 18 months, except
             patients with carcinoma in situ or with non-melanoma skin cancer who may have active
             disease or be in remission for less than 6 months

          -  Patients receiving any other standard or investigational treatment for their
             hematologic malignancy other than 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

          -  Patients who received an allogeneic stem cell transplant =< 90 days from the start of
             therapy

          -  Patients with active >= grade 3 graft versus host disease (GVHD), or receiving
             systemic steroids (> 10 mg/day of prednisone or equivalent) for GVHD

          -  Patients with known active central nervous system (CNS) disease; patients with history
             of active CNS disease should have at least two negative spinal fluid evaluations
             before being considered eligible
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Minimum safety data
Time Frame:4 weeks
Safety Issue:
Description:Safety data will be summarized using frequency and percentage for all patients.

Secondary Outcome Measures

Measure:Overall survival
Time Frame:Up to 4 years
Safety Issue:
Description:Estimated using the Kaplan-Meier methods.
Measure:Disease-free survival
Time Frame:Up to 4 years
Safety Issue:
Description:Estimated using the Kaplan-Meier methods.
Measure:Event-free survival
Time Frame:Up to 4 years
Safety Issue:
Description:Estimated using the Kaplan-Meier methods.
Measure:Duration of complete remission
Time Frame:Up to 4 years
Safety Issue:
Description:Complete remission rates will be estimated along with 95% credible intervals. Estimated using the Kaplan-Meier methods.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

June 29, 2021