A Study of Dasatinib and Rituximab for Relapsed/Refractory Chronic Lymphocytic Leukemia

NCT00949988 | Terminated Phase 1 Results DMC

• 1 other identifier: UCSD 110054 - Prev 080422
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label phase I/II study that will investigate the combination of dasatinib and rituximab therapy in patients with relapsed/refractory CLL. In phase I, eligible subjects will take either 100 mg or 140 mg of dasatinib daily along with rituximab on day 1 of each cycle for 6 cycles. In phase II, eligible subjects will all receive the same dose of dasatinib, as established in the phase I portion, along with rituximab on day 1 of each cycle for 6 cycles. The investigators hypothesize that the combination of dasatinib and rituximab will demonstrate efficacy in the treatment of patients with relapsed/refractory CLL.

Conditions

Chronic Lymphocytic Leukemia

Keywords

Chronic Lymphocytic Leukemia; CLL; Dasatinib; Rituximab; Relapsed; Refractory

Outcome Measures

Primary Outcomes (1)

• Phase I: To Determine the Dose-limiting Toxicities (DLTs) and Maximum Tolerated Dose (MTD) of D+R Therapy in Patients With Relapsed/Refractory CLL

  1 year

Secondary Outcomes (7)

• To Assess the Safety Profile of D+R in Relapsed/Refractory CLL Patients

  2 years

• To Assess Duration of Progression-free Survival

  5 years

• To Assess Minimal Residual Disease (MRD) by Flow Cytometry

  2 years

• To Determine the Effect of Several Prognostic Factors Including CD38 Expression, ZAP-70 Expression, Immunoglobulin Variable Heavy Chain (VH) Gene Mutation Status and Cytogenetic/FISH Profile on Treatment Response.

  2 years

• To Evaluate in CLL Cells Pharmacodynamic (PD) Parameters Including the Following: in Vivo Signal Transduction Events, Levels of Cellular Apoptosis and Regulation of Apoptosis Related Genes and Proteins.

  2 years

Study Arms (2)

Dasatinib - 100 mg (Phase I)

ACTIVE COMPARATOR

Dasatinib - 100 mg (Phase I)

Drug: Dasatinib and Rituximab

Dasatinib - 70 mg (Phase I)

ACTIVE COMPARATOR

Dasatinib - 70 mg (Phase I)

Drug: Dasatinib and Rituximab

Interventions

Dasatinib and Rituximab DRUG

In Phase I, subjects will be enrolled into a "3+3" dose escalation scheme with two dasatinib cohort doses of 70 mg QD and 100 mg QD to be given continuously during each 28-day cycle. All subjects will also receive rituximab 500 mg/m2 on day 1 of each cycle (375 mg/m2 on day 1 of cycle 1 only). There will be a pre-phase for each dose cohort when subjects will receive single-agent dasatinib from days -7 to -1 to allow for PK and PD assessment. Cohorts will be assessed for dose-limiting toxicities for two cycles before accrual of additional

Dasatinib - 100 mg (Phase I); Dasatinib - 70 mg (Phase I)

Eligibility Criteria

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

You may qualify if:

• Confirmed immunohistological diagnosis of B-cell CLL and Rai Stage III or IV disease, or stage 0-II disease that meets NCIWG criteria for active disease as indicated by any one of the following disease-related symptoms:
• Weight loss ≥ 10% within the previous 6 months
• Extreme fatigue
• Fever greater than 100.5 degrees Fahrenheit for ≥ 2 weeks without evidence of infection
• Night sweats without evidence of infection
• Evidence of progressive marrow failure based on the development or worsening of anemia (\< 10 g/dL) or thrombocytopenia (\< 100,000 cells/mL)
• Autoimmune anemia and/or thrombocytopenia poorly responsive to corticosteroid therapy
• Massive (\> 6 cm below the left costal margin) or progressive splenomegaly
• Bulky (\>10 cm in cluster) or progressive lymphadenopathy
• Progressive lymphocytosis with \> 50% increase over a 2-month period, or anticipated doubling time \< 6 months
• Relapsed/ Refractory CLL that has progress with ≥1 prior treatment including a purine nucleoside analog-containing regimen, alkylating agent, or antibody (rituximab or alemtuzumab) or intolerance to purine nucleoside analog-containing therapy or unwilling to receive chemotherapy treatment.
• Age 18 or older
• ECOG Performance Status 0-2 (Appendix B)
• Adequate organ function:
• Serum creatinine \< 2x the institutional upper limit of normal (ULN)

You may not qualify if:

• No prior CLL-related treatment within 28 days before starting treatment with dasatinib.
• No concurrent use of other investigation agent.
• Concurrent medical condition which may increase the risk of toxicity, including:
• Uncontrolled or significant cardiovascular disease, including:
• Myocardial infarction, congestive heart failure or uncontrolled angina within 6 months
• Diagnosed congenital long QT syndrome
• Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes)
• Prolonged QTcF interval on pre-entry ECG (\> 450 msec)
• nd/3rd degree heart block, uncontrolled hypertension or heart rate \< 50
• History of significant bleeding disorder unrelated to CLL, including:
• Diagnosed congenital bleeding disorder (e.g., von Willebrand's disease)
• Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)
• Ongoing or recent significant GI bleeding within 3 months
• Hypokalemia or hypomagnesemia if it cannot be corrected
• Pleural or pericardial effusion of any grade

Sponsors & Collaborators

• University of California, San Diego: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

University of California San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Recurrence

Interventions

Dasatinib; Rituximab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Kimberly Aguilar, Clinical Trials Manager
• Organization: UCSD Moores Cancer Center

k1aguilar@ucsd.edu

858-534-5201

Study Officials

• Januario Castro, M.D.

  Clinical Professor, Blood and Bone Marrow Transplant Division

  PRINCIPAL INVESTIGATOR

• Thomas J Kipps, M.D., Ph.D.

  Professor of Medicine, Evelyn and Edwin Tasch Chair in Cancer Research in the UCSD School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 28, 2009
• First Posted: July 31, 2009
• Study Start: May 1, 2009
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: August 14, 2019
• Results First Posted: August 14, 2019

Record last verified: 2019-07

Locations

US (1)