Safety and Tolerability Study of INNO-406 to Treat Chronic Myeloid Leukemia or Acute Lymphocytic Leukemia

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and effectiveness of INNO-406 in adult patients with imatinib-resistant or intolerant Philadelphia chromosome-positive (Ph+) leukemias.

Detailed Description
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The purpose of this study is to determine the safety, tolerability and pharmacokinetic profile of INNO-406 when administered as a daily oral agent in adult patients with imatinib-resistant or intolerant Philadelphia chromosome-positive (Ph+) leukemias.

Official Title
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A Phase I, Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of INNO-406 in Adult Patients With Imatinib-Resistant or Intolerant Philadelphia Chromosome-Positive (Ph+) Leukemias

Conditions
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Chronic Myeloid Leukemia, Acute Lymphocytic Leukemia

Intervention / Treatment
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* Drug: INNO-406


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a confirmed diagnosis of Ph+ ALL or CML in chronic, accelerated, or blastic phases that are either resistant to or intolerant of imatinib therapy. Be ≥18 years old. Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤2. Have an estimated life expectancy of ≥12 weeks. Be male or non-pregnant, non-lactating female. Patients who are fertile must agree to use an effective barrier method of contraception while on therapy and for 90 days following discontinuation of study drug. Have a negative serum or urine pregnancy test within 7 days prior to the first dose of study drug (if patient is a female of childbearing potential). Have acceptable pre-treatment clinical laboratory results. Exclusion Criteria: Have received chemotherapy ≤1 week from the start of therapy, with the exception of hydroxyurea and corticosteroids. Have received imatinib ≤3 days prior to enrollment or have not recovered from side effects of imatinib therapy. Have impaired cardiac function. Have an active, uncontrolled systemic infection considered opportunistic, life-threatening, or clinically significant at the time of treatment. Have clinically significant acute or chronic liver or renal disease considered unrelated to tumor. Have impaired gastrointestinal function that may significantly alter drug absorption (e.g., uncontrolled vomiting, ulcerative colitis, malabsorption, or small bowel resection). Are pregnant or lactating. Have psychiatric disorder(s) that would interfere with consent, study participation, or follow-up. Have not recovered from acute toxicity of all previous therapy prior to enrollment. Have any other severe concurrent disease and/or uncontrolled medical conditions, which, in the judgment of the investigator, could predispose patients to unacceptable safety risks or compromise compliance with the protocol. Have a history of another primary malignancy that is currently clinically significant or requires active intervention.

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: INNO-406|Oral, twice daily self-administration of 10 mg and/or 50 mg tablets|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of INNO-406 when administered as a single agent to adult patients with imatinib-resistant or intolerant Ph+ leukemias. |  | One year | 
| To determine the safety profile (including acute and chronic toxicities) and tolerability of INNO-406 in this patient population. |  | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the pharmacokinetic (PK) profile of INNO-406. |  | One year | 
| To assess BCR-ABL transcript levels and to analyze BCR-ABL mutations. |  | One year | 
| To assess leukemia response rates in this patient population. |  | One year |