Study of Immune Response Modifier in the Treatment of Hematologic Malignancies

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the anti-tumor activity of 852A when used to treat certain hematologic malignancies not responding to standard treatment.

Detailed Description
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852A will be administered as a subcutaneous injection (SC) 2 times per week for 12 weeks (24 doses) with provisions for dose escalation or reduction based on tolerability

Official Title
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Phase II Study of 852A Administered Subcutaneously in Patients With Hematologic Malignancies Not Responding to Standard Treatment

Conditions
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Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma, Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: 852A


Participation Criteria
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Eligibility Criteria
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Subjects are eligible for the study if they meet all of the following Inclusion Criteria: Diagnosis of one of the following hematologic malignancies not responding to at least 2 standard treatment regimens. Any criteria for persistent or recurrent disease acceptable, i.e. ≥5% blasts for acute leukemia. acute lymphoblastic leukemia (ALL) acute myeloid leukemia (AML) non-Hodgkin's lymphoma (NHL) Hodgkin's lymphoma (HL) multiple myeloma (MM) chronic lymphocytic leukemia (CLL) Performance status - Karnofsky > 50% for patients > 10 years of age or Lansky >50% for patients < 10 year of age Normal organ function within 14 days of study entry If female and of childbearing potential, are willing to use adequate contraception (hormonal, barrier method, abstinence) prior to study entry and for the duration of study participation. A female is considered to be of childbearing potential unless she has had her uterus removed, had a double oophorectomy, or has been amenorrheic for at least 6 months after chemotherapy Exclusion Criteria: Had/have the following prior/concurrent therapy: Systemic corticosteroids (oral or injectable) within 7 days of first dose of 852A (topical or inhaled steroids are allowed) Investigational drugs/agents within 14 days of first dose of 852A Immunosuppressive therapy, including cytotoxic agents within 14 days of first dose of 852A (nitrosoureas within 30 days of first dose) Drugs known to induce QT interval prolongation and/or induce Torsades De Pointes unless best available drug required to treat life-threatening conditions Radiotherapy within 4 weeks of the first dose of 852A Hematopoietic cell transplantation 4 weeks of first dose of 852A Active infection or fever > 38.5°C within 3 days of first dose of 852A Cardiac ischemia, cardiac arrhythmias or congestive heart failure uncontrolled by medication History of, or clinical evidence of, a condition which, in the opinion of the investigator, could confound the results of the study or put the subject at undue risk Uncontrolled intercurrent or chronic illness Active autoimmune disease requiring immunosuppressive therapy within 30 days Active hepatitis B or C with evidence of ongoing viral replication Hyperthyroidism Uncontrolled seizure disorder Active coagulation disorder not controlled with medication Pregnant or lactating Concurrent malignancy (if in remission, at least 5 years disease free) except for localized (in-situ) disease, basal carcinomas and cutaneous squamous cell carcinomas adequately treated Proven active central nervous system (CNS) disease Human Immunodeficiency Virus (HIV) positive Congenital long QT syndrome or abnormal baseline QTc interval (> 450 msec in males and > 470 msec in females) after Bazett's correction (QTc msec = QT msec / square root of the RR interval in seconds) on screening electrocardiogram (ECG).
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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 852A Treatment<br>Patients receiving at least one dose of 852A. | Drug: 852A<br>* Subcutaneous injection 0.6 mg/m2 2 times/week/12 weeks, may increase by 0.2 mg/m2 up to 1.2 mg/m2.<br>* Other names: S-32865;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With 852A Response Using Modified Response Evaluation Criteria in Solid Tumors | Stable disease in Non-Hogkin's Lymphoma = disease that does not satisfy complete (complete regression), partial (> or = 50% reduction) or progressive disease (increase of 25%) by at least a 4-week period. Since Acute Myelogenous Leukemia is not a solid tumor, Complete Response (CR) = <5% blasts with hematopoietic recovery (absolute neutrophil count >500) at 4 weeks. | Up to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Who Received Steroids | Number of patients who received steroids allowing successful continuation of therapy. | Up to Week 12 | 
| Measure of Immune Activation With Correlative Laboratory Studies |  | Up to Week 12 | 
| Peak Concentrations of 852A | Measurement of peak concentrations of 852A to correlate the side effects of tolerability in patients. | Up to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Leukemia, Lymphoma, Myeloma, Hematology, 852A, IRM, Oncology