Sotrastaurin Acetate in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia, Prolymphocytic Leukemia, or Richter's Transformation

NCT02285244 | Withdrawn Phase 2 DMC

• 3 other identifiers: OSU-14026NCI-2014-02002COEB071XUS01T
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase II trial studies how well sotrastaurin acetate works in treating patients with chronic lymphocytic leukemia, small lymphocytic leukemia, prolymphocytic leukemia, or Richter's transformation that has returned or that does not respond to treatment. Sotrastaurin acetate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Conditions

Prolymphocytic Leukemia; Recurrent Mantle Cell Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Richter Syndrome

Outcome Measures

Primary Outcomes (1)

• Proportion of CLL/SLL/PLL/RT patients who achieve an objective clinical response, estimated by the number of complete, partial, or partial responses with lymphocytosis divided by the total number of evaluable patients

  Categories of response for CLL and PLL patients defined according to criteria published by the International Workshop on CLL. Response for SLL/RT patients will be according to revised response criteria for malignant lymphoma. The objective response rate for all evaluable patients in the phase II study will be calculated with an exact 95% binomial confidence interval (assuming that the number of patients who respond is binomially distributed).

  Up to 9 months

Secondary Outcomes (18)

• Response duration

  From the time at which criteria for CR, PR, or PR with lymphocytosis is first assessed until the date at which recurrent or progressive disease or death due to disease is documented, assessed up to 3 years

• Progression free survival (PFS)

  Time from the first dose of the study drug until disease progression or death from any cause, assessed up to 3 years

• Overall survival (OS)

  Time from the first dose of the study drug until death, assessed up to 3 years

• Rate of objective clinical response (CR, PR) (optional PLCG2 enriched cohort, if activated)

  Up to 3 years

• Response duration (optional PLCG2 enriched cohort, if activated)

  From the time at which criteria for CR, PR, or PR with lymphocytosis is first assessed until the date at which recurrent or progressive disease or death due to disease is documented, assessed up to 3 years

Study Arms (1)

Treatment (sotrastaurin acetate)

EXPERIMENTAL

Patients receive sotrastaurin acetate PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: sotrastaurin acetate; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

sotrastaurin acetate DRUG

Given PO

Also known as: AEB 071, AEB071

Treatment (sotrastaurin acetate)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (sotrastaurin acetate)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (sotrastaurin acetate)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Life expectancy \>= 2 months
• Appropriate histologic diagnosis (a) or (b):
• (a) Histologically documented diagnosis of intermediate or high risk CLL/SLL, B-PLL, and RT arising from CLL/SLL according to the 2008 guidelines, meeting criteria for active disease requiring treatment:
• Evidence of marrow failure as manifested by the development or worsening of anemia or thrombocytopenia (not attributable to autoimmune hemolytic anemia or thrombocytopenia)
• Massive (\>= 6 cm below the costal margin), progressive or symptomatic splenomegaly
• Massive nodes (\>= 10 cm) or progressive or symptomatic lymphadenopathy
• Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy
• Constitutional symptoms including any of the following:
• Unintentional weight loss of 10% or more within 6 mos.
• Significant fatigue limiting activity
• Fevers \>= 100.5 degrees F for 2 weeks or more without evidence of infection
• Night sweats \> 1 month without evidence of infection
• Need for cytoreduction prior to stem cell transplantation
• (b) Pathologically documented MCL \[defined as either t(11;14) or overexpression of cyclin D1\] for the MCL pilot study

You may not qualify if:

• Prior therapy as follows:
• Major surgery within 2 weeks
• Corticosteroids greater than 20 mg/day prednisone (or equivalent) within 2 weeks unless used by inhalation or topical route, or unless necessary for premedication before iodinated contrast dye, or for autoimmune hemolytic anemia
• Cytotoxic chemotherapy or biologic therapy within 4 weeks, excepting BCR kinase inhibitors for which no wash out is required, or
• Nitrosoureas within the 6 weeks of the planned first dose of the study drug
• Failure to recover toxicity from prior chemo- or radiotherapy to grade 1
• Known active leukemia or lymphoma of the central nervous system (CNS) requiring therapy
• Inadequate bone marrow function/hematopoietic reserve, except in the case of documented bone-marrow involvement: absolute neutrophil count (ANC) \< 1 x 10\^9/L
• Inadequate bone marrow function/hematopoietic reserve, except in the case of documented bone-marrow involvement: platelets \< 30 x 10\^9/L
• Serum total bilirubin \> 2 x ULN (upper limit of normal)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2.5 x ULN, or \> 5 x ULN if CLL/lymphoma is present in the liver
• Estimated glomerular filtration rate (GFR) \< 30 mL/min
• Patients who are receiving treatment with medications that are known to be strong inducers or inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5) and CYP3A4/5 substrates with QT prolongation risk that cannot be discontinued prior to study entry
• Clinically significant cardiac diseases, including any of the following:
• History or presence of ventricular tachyarrhythmia

Sponsors & Collaborators

• James Blachly: lead
• Novartis: collaborator

Related Links

• The Jamesline

MeSH Terms

Conditions

Leukemia, Prolymphocytic; Lymphoma, Mantle-Cell; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

sotrastaurin

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• James Blachly, MD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 4, 2014
• First Posted: November 6, 2014
• Study Start: March 12, 2015
• Primary Completion: March 12, 2015
• Study Completion: March 12, 2015
• Last Updated: April 5, 2017

Record last verified: 2017-04