7-Hydroxystaurosporine and Perifosine in Treating Patients With Relapsed or Refractory Acute Leukemia, Chronic Myelogenous Leukemia or High Risk Myelodysplastic Syndromes

Recurrent Adult Acute Myeloid Leukemia Clinical Trial

Official title: A Phase 1 Study of UCN-01 in Combination With Perifosine in Patients With Relapsed and Refractory Acute Leukemias and High Risk MDS

Status Completed

Clinical Trial Summary

This phase I trial is studying the side effects and best dose of 7-hydroxystaurosporine when given together with perifosine in treating patients with relapsed or refractory acute leukemia, chronic myelogenous leukemia, or myelodysplastic syndromes. 7-Hydroxystaurosporine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as perifosine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving 7-hydroxystaurosporine together with perifosine may kill more cancer cells.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. Define the maximum tolerated dose and recommended phase II dose of UCN-01 (7-hydroxystaurosporine) administered after perifosine in patients with relapsed or refractory acute leukemia, chronic myelogenous leukemia, or high risk myelodysplastic disorders.

SECONDARY OBJECTIVES:

I. Evaluate the safety and toxicity of UCN-01 administered after perifosine in these patients.

II. Evaluate the safety and toxicity of perifosine administered after UCN-01 in these patients.

III. Document responses in patients treated with this regimen. IV. Observe the pharmacokinetics of both perifosine and UCN-01 when administered in combination.

V. Study the pharmacodynamics of perifosine alone, UCN-01 alone, and in combination in leukemic blast cells.

OUTLINE: This is a multicenter, dose-escalation study of 7-hydroxystaurosporine. The first patients enrolled in the study are assigned to arm 1. Once the maximum tolerated dose (MTD) is determined in arm 1, subsequent patients are enrolled in arm 2.

ARM 1: Patients receive a loading dose of oral perifosine every 6 hours on day 1 followed by a maintenance dose once daily on days 2-28 of course 1 and then once daily on days 1-28 in all subsequent courses. Patients also receive 7-hydroxystaurosporine intravenously (IV) over 3 hours on day 4. Cohorts of 3-6 patients receive escalating doses of 7-hydroxystaurosporine until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

ARM 2: Patients receive 7-hydroxystaurosporine IV over 3 hours on day 1 at the MTD determined in group I. Patients also receive oral perifosine as a loading dose every 6 hours on day 4 followed by a maintenance dose once daily on days 5-28 of course 1 and then once daily on days 1-28 in all subsequent courses. In both groups, treatment repeats every 28 days for ≥ 2 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete remission (CR) or a CR with incomplete hematologic recovery receive 4 additional courses beyond documentation of CR. Patients who achieve a partial remission or hematologic improvement may continue treatment in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 30 days and then periodically thereafter. ;

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Accelerated Phase Chronic Myelogenous Leukemia
• Adult Acute Megakaryoblastic Leukemia (M7)
• Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
• Adult Acute Monoblastic Leukemia (M5a)
• Adult Acute Monocytic Leukemia (M5b)
• Adult Acute Myeloblastic Leukemia With Maturation (M2)
• Adult Acute Myeloblastic Leukemia Without Maturation (M1)
• Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
• Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
• Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
• Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
• Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
• Adult Acute Myelomonocytic Leukemia (M4)
• Adult Acute Promyelocytic Leukemia (M3)
• Adult Erythroleukemia (M6a)
• Adult Pure Erythroid Leukemia (M6b)
• Blast Crisis
• Blastic Phase Chronic Myelogenous Leukemia
• Leukemia
• Leukemia, Erythroblastic, Acute
• Leukemia, Lymphoid
• Leukemia, Megakaryoblastic, Acute
• Leukemia, Monocytic, Acute
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Myelomonocytic, Acute
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Promyelocytic, Acute
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Neoplasms
• Myeloproliferative Disorders
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia
• Previously Treated Myelodysplastic Syndromes
• Recurrent Adult Acute Lymphoblastic Leukemia
• Recurrent Adult Acute Myeloid Leukemia
• Relapsing Chronic Myelogenous Leukemia
• Secondary Acute Myeloid Leukemia
• T-cell Adult Acute Lymphoblastic Leukemia
• Untreated Adult Acute Lymphoblastic Leukemia
• Untreated Adult Acute Myeloid Leukemia

• NCT number: NCT00301938
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Completed
• Phase: Phase 1
• Start date: December 2005