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Hu8F4 in Treating Patients With Advanced Hematologic Malignancies

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ClinicalTrials.gov Identifier: NCT02530034
Recruitment Status : Recruiting
First Posted : August 20, 2015
Last Update Posted : September 19, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive High Risk Myelodysplastic Syndrome HLA-A2 Positive Cells Present Myelodysplastic Syndrome With Excess Blasts-1 Myelodysplastic Syndrome With Excess Blasts-2 Myelofibrosis Previously Treated Myelodysplastic Syndrome Recurrent Acute Myeloid Leukemia Recurrent Chronic Myelomonocytic Leukemia Refractory Chronic Myelomonocytic Leukemia Secondary Acute Myeloid Leukemia Drug: Anti-PR1/HLA-A2 Monoclonal Antibody Hu8F4 Other: Laboratory Biomarker Analysis Other: Pharmacological Study Phase 1

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) 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. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Hu8F4 in Patients With Advanced Hematologic Malignancies
Actual Study Start Date : January 31, 2019
Estimated Primary Completion Date : January 31, 2022
Estimated Study Completion Date : January 31, 2022


Arm Intervention/treatment
Experimental: Treatment (Hu8F4)
Patients receive anti-PR1/HLA-A2 monoclonal antibody Hu8F4 IV over 60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Anti-PR1/HLA-A2 Monoclonal Antibody Hu8F4
Given IV
Other Name: Hu8F4

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Pharmacological Study
Correlative studies




Primary Outcome Measures :
  1. (MTD) of Hu8F4 when administered intravenously in patients with leukemia or myelodysplastic syndrome (MDS). [ Time Frame: 4 weeks ]
    The highest dose level at which </=1 patient experiences dose limiting toxicity (DLT) will be defined as the MTD and will be selected as the recommended phase 2 dose. DLT is 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 :
  1. Overall survival [ Time Frame: Up to 4 years ]
    Estimated using the Kaplan-Meier methods.

  2. Disease-free survival [ Time Frame: Up to 4 years ]
    Estimated using the Kaplan-Meier methods.

  3. Event-free survival [ Time Frame: Up to 4 years ]
    Estimated using the Kaplan-Meier methods.

  4. Duration of complete remission [ Time Frame: Up to 4 years ]
    Complete remission rates will be estimated along with 95% credible intervals. Estimated using the Kaplan-Meier methods.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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 Dynamic International Prognostic Scoring System [DIPSS]-plus high risk score)
  • 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
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • 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
  • 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/m^2) given for palliative purposes for which a washout of >/=5 days is required
  • Clinically significant toxicities from prior chemotherapy must not be greater than grade 1
  • Serum creatinine =< 1.5 x the upper limit of normal
  • Total bilirubin =< 1.5 x the upper limit of normal unless considered due to Gilbert's syndrome
  • 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 degree 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 < 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
  • 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 a stem cell transplant =< 12 months from the start of therapy
  • Patients with active graft versus host disease (GVHD), or receiving therapy 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02530034


Contacts
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Contact: Jorge Cortes 713-794-5783 jcortes@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Jorge E. Cortes    713-794-5783      
Principal Investigator: Jorge E. Cortes         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Jorge Cortes M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02530034     History of Changes
Other Study ID Numbers: 2014-0057
NCI-2015-02131 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
P-TRP-2447-14
2014-0057 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
P50CA100632 ( U.S. NIH Grant/Contract )
First Posted: August 20, 2015    Key Record Dates
Last Update Posted: September 19, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Preleukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Blast Crisis
Myelodysplastic Syndromes
Anemia, Refractory, with Excess of Blasts
Syndrome
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Cell Transformation, Neoplastic
Carcinogenesis
Neoplastic Processes
Anemia, Refractory
Anemia
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunologic Factors