Study of ENMD-2076 in Patients With Relapsed or Refractory Hematological Malignancies

Study Overview
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Brief Summary
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To define the maximum tolerated dose of oral daily ENMD 2076 in patients with relapsed or refractory hematological malignancies

Official Title
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A Phase 1 Study of ENMD-2076 in Patients With Relapsed or Refractory Hematological Malignancies

Conditions
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Relapsed or Refractory Hematological Malignancies

Intervention / Treatment
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* Drug: ENMD-2076


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have relapsed/refractory hematological malignancy for which no standard therapies are anticipated to result in a durable remission. Patients with poor-risk myelodysplasia (MDS) [i.e., IPSS ≥ 1.5] or chronic myelomonocytic leukemia (CMML) are also candidates for this protocol. Relapsed/refractory leukemias include acute non lymphocytic leukemia (AML) by WHO classification, acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), or chronic myelogenous leukemia (CML) in blast crisis. Patients with agnogenic myeloid metaplasia (AMM) are also eligible. Patients with relapsed or refractory lymphoma or myeloma may also participate. Age ≥18 years. Adequate performance status 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 and adequate recovery from prior toxicities. If the patient had a transplant, at least 6 months must have passed before initiation of treatment on this protocol and stable graft versus host disease (no change in severity) for 4 weeks preceding study entry (if applicable). Persistent clinically significant chronic toxicities from prior therapy must have resolved to baseline or NCI CTCAE Grade < 1 Adequate laboratory results within 10 days of ENMD-2076 administration (unless the abnormality is considered attributable to leukemia) Exclusion Criteria: Pregnant or breast-feeding women. Clinical evidence of bowel obstruction, active uncontrolled malabsorption syndromes or a history of total gastrectomy. Impaired cardiac function including myocardial infarction within previous 3 months, symptomatic coronary artery disease, arrhythmias not controlled by medication, uncontrolled hypertension, or uncontrolled congestive heart failure. Blood pressure must be < 150/90 at the time of enrollment. Receiving any other treatment for their disease QTc prolongation defined as ≥ 470 ms.

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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: ENMD-2076<br>* capsule, dose escalation, taken orally, daily in 28 day cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Define the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of oral daily ENMD 2076 by evaluation of adverse events |  | Day 1 through first cycle of therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and toxicity of repeated oral dosing of ENMD 2076 |  | Throughout study participation | 
| Describe any preliminary evidence of anti-cancer effects of ENMD-2076 in patients with hematological malignancies |  | monthly | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Leukemia, Hematologic neoplasms