Hu8F4 in Treating Patients With Advanced Hematologic Malignancies

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase I Study of Hu8F4 in Patients With Advanced Hematologic Malignancies

Conditions
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Myelofibrosis, 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, Recurrent Acute Myeloid Leukemia, Recurrent Chronic Myelomonocytic Leukemia, Refractory Chronic Myelomonocytic Leukemia, Secondary Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Anti-PR1/HLA-A2 Monoclonal Antibody Hu8F4
* Other: Laboratory Biomarker Analysis
* Other: Pharmacological Study


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (Hu8F4)<br>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. | Drug: Anti-PR1/HLA-A2 Monoclonal Antibody Hu8F4<br>* Given IV<br>* Other names: Hu8F4;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Pharmacological Study<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Minimum safety data | Safety data will be summarized using frequency and percentage for all patients. | 4 weeks | 
| Biologically-effective dose | Safety data will be summarized using frequency and percentage for all patients. | 4 weeks | 

Secondary Outcome Measures

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