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 anti-PR1/HLA-A2 monoclonal antibody 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 Syndromes
  • Primary Myelofibrosis
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase I Study of Hu8F4 in 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: P-TRP-2447-14
  • SECONDARY ID: NCI-2015-02131
  • NCT ID: NCT02530034

Conditions

  • Leukemia

Interventions

DrugSynonymsArms
Hu8F4Hu8F4

Purpose

The goal of this clinical research study is to find the highest tolerable dose of Hu8F4 that can be given to patients with advanced leukemia. This is the first study using Hu8F4 in humans.

Detailed Description

      Study Groups:

      If you are found to be eligible to take part in this study, you will be assigned to a dose
      level of Hu8F4 based on when you join this study. Up to 5 dose levels of Hu8F4 will be
      tested. One (1)-6 participants will be enrolled at each dose level. The first group of
      participants will receive the lowest dose level. Each new group will receive a higher dose
      than the group before it, if no intolerable side effects were seen. This will continue until
      the highest tolerable dose of Hu8F4 is found.

      Once the highest tolerable dose is found, additional participants will be enrolled so that at
      least 6 participants with each cancer type are enrolled. Additional 3 groups of 10
      participants each may be added for a specific leukemia type in "expansion groups" after the
      highest tolerable dose is found.

      Study Drug Administration:

      You will receive the Hu8F4 by vein over about 60 minutes on Days 1 and 15 of each 28-day
      cycle.

      Study Visits:

      Before you take the study drug you will have a bone marrow biopsy/aspiration. To collect a
      bone marrow biopsy/aspirate, an area of the hip or other site is numbed with anesthetic, and
      a small amount of bone marrow and bone is withdrawn through a large needle.

      During Week 1 of Cycle 1:

        -  You will have a physical exam.

        -  Blood (about 2 teaspoons) will be drawn for routine tests. If these tests have been
           performed within 3 days, they do not need to be repeated.

        -  If you can have children, blood (about 1 teaspoon) or urine will be collected for a
           pregnancy test.

        -  Blood (about 4 tablespoons) will be drawn before you receive the study drug for testing
           for the effects of Hu8F4 and to test for antibodies to Hu8F4. Antibodies are created by
           the immune system and may attack foreign cells or substances, such as the study drug.

        -  Blood (about 2 teaspoons each time) will be drawn for pharmacokinetic (PK) testing 7
           times over the 24 hours after the dose. PK testing measures the amount of study drug in
           the body at different time points.

      On the days you receive the 1st and 2nd dose of the study drug on Cycle 1, blood (about 2
      teaspoons) will be drawn for PK testing before and at different times after the
      administration, on that day and 1, 2, 3, 5 and 8 days after administration. All other times
      you receive study drug you will have a blood collection (about 2 teaspoons) before and right
      after administration.

      During Weeks 2-4 of Cycle 1, blood (about 5 tablespoons) will be drawn for routine tests, to
      check for effects of Hu8F4 (Weeks 2-4), and to test for antibodies to Hu8F4 (Week 2 and Week
      4).

      During Week 4 of Cycle 1, you will have bone marrow biopsy/aspiration to check the status of
      the disease.

      Every 3 months after week 4 of Cycle 1 you will have a blood collection (about 2 teaspoons)
      to test for antibodies to Hu8F4.

      During Week 1 of Cycle 2:

        -  You will have a physical exam.

        -  Blood (about 2 teaspoons) will be drawn for routine tests. If these tests have been
           performed within 3 days, they do not need to be repeated.

        -  Blood (about 2 tablespoons) will be drawn to check for the effects of Hu8F4

        -  Blood (about 1 teaspoon each time) will be drawn before and after you receive the study
           drug for PK testing.

      During Weeks 2-4 of Cycles 2 and 3, blood (about 3 tablespoons) will be drawn for routine
      tests. Before and after receiving the drug in Cycle 2 and 3, this blood will also be used to
      check for PK testing.

      During Week 1 of Cycle 3:

        -  You will have a physical exam.

        -  Blood (about 2 teaspoons) will be drawn for routine tests. If these tests have been
           performed within 3 days, they do not need to be repeated.

        -  Blood (about 2 tablespoons) will be drawn to check for the effects of Hu8F4.

      During Week 1 of Cycles 4 and beyond:

        -  You will have a physical exam.

        -  Blood (about 2 teaspoons) will be drawn to check for the effects of Hu8F4.

      Every 2-4 weeks of Cycles 3 and beyond, blood (about 2 teaspoons) will be drawn for routine
      tests.

      Every 1-3 cycles, you will have a bone marrow aspiration to check the status of the disease.

      Length of Study:

      You may continue taking the study drug for as long as the doctor thinks it is in your best
      interest. You will no longer be able to take the study drug if the disease gets worse, if
      intolerable side effects occur, or if you are unable to follow study directions.

      This is an investigational study. Hu8F4 is not FDA approved or commercially available. It is
      currently being used for research purposes only. The study doctor can explain how the study
      drug is designed to work.

      Up to 60 participants will be enrolled in this study. All will take part at MD Anderson.
    

Trial Arms

NameTypeDescriptionInterventions
Hu8F4ExperimentalPhase I Starting dose of Hu8F4 is 1 mg by vein over about 30 minutes on Days 0, 7, 14, and 21 of each 28-day cycle.
  • Hu8F4
Myelodysplastic Syndromes or Chronic Myelomonocytic LeukemiaExperimentalPhase II Starting dose of Hu8F4 is the maximum tolerated dose from Phase I.
  • Hu8F4
Acute Myeloid LeukemiaExperimentalPhase II Starting dose of Hu8F4 is the maximum tolerated dose from Phase I.
  • Hu8F4
Chronic Myeloid Leukemia in Blast PhaseExperimentalPhase II Starting dose of Hu8F4 is the maximum tolerated dose from Phase I.
  • Hu8F4

Eligibility Criteria

        Inclusion Criteria:

          1. 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 WHO classification, or any
             WHO subset with IPSS intermediate-2 or high, or any patients that has 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 DIPSS-plus
             high risk score)

          2. Patients must have relapsed/refractory disease. Patients with secondary AML (including
             those progressing from MDS or myeloproliferative neoplasm -MPN-, and those with AML
             secondary to chemotherapy or radiotherapy for other malignancies) are eligible whether
             they have received prior therapy for AML or not. Patients with high-risk myelofibrosis
             are also eligible regardless of whether they have received prior therapy or not.

          3. Age >/= 18 years

          4. ECOG performance status of 0-2

          5. 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

          6. Patients must have HLA-A2 phenotype

          7. Must be able and willing to give written informed consent

          8. In the absence of rapidly progressing disease, the interval from prior treatment to
             time of study drug administration should be at least 2 weeks for cytotoxic agents, or
             at least 5 half-lives for noncytotoxic agents. Exceptions are 1) hydroxyurea that
             requires no washout prior to the start of Hu8F4, and 2) up to 2 doses of single-agent
             cytarabine (up to 3 grams/m2) given for palliative purposes for which a washout of
             >/=5 days is required

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

         10. Patients must have the following clinical laboratory values unless considered due to
             leukemic organ involvement: a). Serum creatinine </= 1.5x the upper limit of normal.
             b). Total bilirubin </= 1.5x the upper limit of normal unless considered due to
             Gilbert's syndrome. c). Alanine aminotransferase (ALT) </= 3x the upper limit of
             normal unless considered due to leukemic involvement.

        Exclusion Criteria:

          1. Uncontrolled intercurrent illness including, but not limited to uncontrolled infection
             (patients must have no temperature >/=38.3°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 NY Heart Association class III or IV.

          2. Patients with current active malignancies or any remission for <24 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

          3. Patients receiving any other standard or investigational treatment for their
             hematologic malignancy other than supportive care.

          4. Patients who have had any major surgical procedure within 14 days of Day 1

          5. Patients with known central nervous system infiltration with leukemia

          6. Patients who received a stem cell transplant </=12 months from the start of therapy.

          7. Patients with active graft versus host disease (GVHD), or receiving therapy for GVHD.

          8. Patients with known active 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:Maximum Tolerated Dose (MTD) of Hu8F4 During Dose Escalation
Time Frame:28 day cycle
Safety Issue:
Description:The highest dose level at which ≤1 patient experiences dose limiting toxicity (DLT) defined as MTD. DLT defined as any clinically significant non-hematologic adverse event or abnormal laboratory value occurring during the first cycle on study that is not related to disease, comorbidities or concomitant medications.

Secondary Outcome Measures

Measure:Overall Survival Estimated Using the Kaplan-Meier Methods
Time Frame:3 years
Safety Issue:
Description:
Measure:Disease-Free Survival Estimated Using the Kaplan-Meier Methods
Time Frame:3 years
Safety Issue:
Description:
Measure:Event-Free Survival and Duration of Complete Remission Estimated Using the Kaplan-Meier Methods
Time Frame:3 years
Safety Issue:
Description:
Measure:Duration of Complete Remission Estimated Using the Kaplan-Meier Methods
Time Frame:3 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Leukemia
  • Advanced Hematologic Malignancies
  • Myelodysplastic syndrome
  • MDS
  • Chronic myelomonocytic leukemia
  • CMML
  • Acute myeloid leukemia
  • AML
  • Myelofibrosis
  • Hu8F4

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