Trial record 5 of 8 for:    immune thrombocytopenia OR immune thrombocytopenic purpura OR idiopathic thrombocytopenic purpura | Open Studies | NIH, U.S. Fed

Imprime PGG, Alemtuzumab, and Rituximab in Treating Patients With High Risk Chronic Lymphocytic Leukemia

This study is currently recruiting participants.
Verified February 2014 by Mayo Clinic
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01269385
First received: December 23, 2010
Last updated: February 18, 2014
Last verified: February 2014
  Purpose

RATIONALE: Monoclonal antibodies, such as alemtuzumab and rituximab, can kill chronic lymphocytic leukemia (CLL) cells and are effective therapies for this disease. Biological therapies, such as Imprime PGG (poly-(1-6)-beta-glucotriosyl-(1-3)-beta-glucopyranose), may stimulate the immune system in different ways and help monoclonal antibodies kill CLL cells. Giving PGG beta-glucan together with alemtuzumab and rituximab could make therapy with monoclonal antibodies, such as alemtuzumab and rituximab, more effective.

PURPOSE: This phase I/II trial is studying the side effects and best dose of PGG beta-glucan when given together with alemtuzumab and rituximab and to see how well it works in treating patients with earlier stage high-risk chronic lymphocytic leukemia.


Condition Intervention Phase
B-cell Chronic Lymphocytic Leukemia
Refractory Chronic Lymphocytic Leukemia
Stage 0 Chronic Lymphocytic Leukemia
Stage I Chronic Lymphocytic Leukemia
Stage II Chronic Lymphocytic Leukemia
Biological: alemtuzumab
Biological: rituximab
Drug: PGG beta-glucan
Other: flow cytometry
Other: laboratory biomarker analysis
Genetic: DNA analysis
Genetic: fluorescence in situ hybridization
Genetic: polymerase chain reaction
Genetic: polymorphism analysis
Genetic: mutation analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Early Treatment of High Risk Chronic Lymphocytic Leukemia With Alemtuzumab, Rituximab, and PGG Beta-Glucan: A Phase I/II Trial

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • To determine the maximum tolerated dose (MTD) of PGG beta glucan in combination with alemtuzumab and rituximab (Phase I) [ Time Frame: At least 5 weeks ] [ Designated as safety issue: Yes ]
  • Proportion of complete responses (Phase II) [ Time Frame: 3 months after the completion of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall response rate as estimated by the total number of complete responses or partial responses (CR or PR) divided by the total number of evaluable patients (Phase II) [ Time Frame: 3 months after the completion of treatment ] [ Designated as safety issue: No ]
  • Time to disease progression (Phase II) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Duration of response for all evaluable patients who have achieved an objective response (Phase II) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Time to subsequent therapy (Phase II) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • The number and severity of all adverse events (Phase I) [ Time Frame: At least 5 weeks ] [ Designated as safety issue: Yes ]
  • Toxicity profile, including non-hematologic toxicities; hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia; and overall toxicity incidence as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 (Phase I) [ Time Frame: At least 5 weeks ] [ Designated as safety issue: Yes ]
  • The number and severity of grade 3+ adverse events (Phase I) [ Time Frame: At least 5 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 55
Study Start Date: January 2011
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive PGG beta-glucan IV over 2-4 hours on days 1, 5, 10, 17, 24, and 31; alemtuzumab subcutaneously on days 3, 4, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; and rituximab IV on days 10, 17, 24, and 31. Treatment continues in the absence of disease progression or unacceptable toxicity.
Biological: alemtuzumab
Given subcutaneously
Other Names:
  • anti-CD52 monoclonal antibody
  • Campath-1H
  • MoAb CD52
  • Monoclonal Antibody Campath-1H
  • Monoclonal Antibody CD52
Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Drug: PGG beta-glucan
Given IV
Other Name: Imprime PGG
Other: flow cytometry
Correlative studies
Other: laboratory biomarker analysis
Correlative studies
Genetic: DNA analysis
Correlative studies
Genetic: fluorescence in situ hybridization
Correlative studies
Other Name: fluorescence in situ hybridization (FISH)
Genetic: polymerase chain reaction
Correlative studies
Other Name: PCR
Genetic: polymorphism analysis
Correlative studies
Genetic: mutation analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of PGG beta glucan in combination with alemtuzumab and rituximab. (Phase I) II. Assess the rate of complete response of patients with high-risk, early-intermediate stage CLL who are treated with alemtuzumab, rituximab, and PGG beta glucan before meeting standard National Cancer Institute-International Workshop on Chronic Lymphocytic Leukemia (NCI-IWCLL) criteria (Hallek, Cheson et al. 2008) for treatment. (Phase II)

SECONDARY OBJECTIVES:

I. To monitor and assess toxicity of this regimen. II. Clinical evaluation of toxicity. III. Serial monitoring of cytomegalovirus (CMV) viral load by polymerase chain reaction (PCR).

IV. To assess the rate of overall response in CLL patients using this treatment regimen.

V. To determine time to progression, time to next treatment, and duration of response in CLL patients using this treatment regimen.

TERTIARY OBJECTIVES:

I. To assess the correlation between the individual prognostic markers (17p-, 11q-, unmutated VH gene, use of VH3-21, ZAP70+, CD38+) and clinical outcome.

II. To assess response to this combination regimen using an expanded definition of response, including bone marrow studies with immunohistochemical studies for residual CLL cells and sensitive flow cytometry for minimal residual disease in patients in complete clinical remission.

OUTLINE: This is phase I, dose-escalation study of PGG beta-glucan followed by a phase II study.

Patients receive PGG beta-glucan intravenously (IV) over 2-4 hours on days 1, 5, 10, 17, 24, and 31; alemtuzumab subcutaneously (SC) on days 3, 4, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; and rituximab IV on days 10, 17, 24, and 31. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up monthly for 3 months, every 3 months for 1 year, and then every 6 months for 5 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of CLL (Hallek, Cheson et al. 2008) manifested by: Minimum threshold peripheral lymphocyte count of 5 x 10^9/L AND immunophenotypic demonstrations of a population of B lymphocytes (as defined by CD19+) which are monoclonal (light chain exclusion); CLL will be diagnosed if these cells have >= 3 of the following characteristics: CD5+, CD23+, dim surface light chain expression, dim surface CD20 expression AND fluorescence in situ hybridization (FISH) analysis is negative for IGH/CCND1 and/or immunostaining is negative for cyclin D1 expression
  • >= 1 of the following poor prognosis factors: unmutated IGHV (< 2%) AND CD38 expression (>= 30% cells positive on flow cytometry); unmutated IGHV (< 2%) AND ZAP-70 expression (>= 20% cells positive on flow cytometry); use of VH3-21 gene segment irrespective of mutation status AND CD38 expression (>= 30% cells positive on flow cytometry); use of VH3-21 gene segment irrespective of mutation status AND ZAP-70 expression (>= 20% cells positive on flow cytometry); 11q22-; 17p13-
  • Rai classification Stage 0, I or II that does not meet standard NCI-IWCLL criteria for treatment of CLL (Hallek, Cheson et al. 2008)
  • Limited CLL disease burden with no lymph nodes > 5 cm in any diameter and splenomegaly < 6 cm below left costal margin in midclavicular line at rest
  • Creatinine =< 1.5 x upper normal limit (UNL)
  • Total bilirubin =< 3.0 x UNL; if total is elevated, a direct bilirubin should be performed and should be =< 1.5 x UNL
  • AST =< 3.0 x UNL
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0, 1, or 2
  • Negative serum pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
  • Provide informed written consent
  • Willing to return to a Lymphoma Specialized Program of Research Excellence (SPORE) enrolling institution for follow-up
  • Willing to provide blood samples for correlative research purposes

Exclusion Criteria:

  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • New York Heart Association Class III or IV heart disease
  • Recent myocardial infarction (< 1 month)
  • Uncontrolled infection
  • Infection with the human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), serological evidence of active hepatitis B infection (HBsAg or HBeAg positive) or positive hepatitis C serology, as further severe immunosuppression with this regimen may occur
  • Evidence of active autoimmune hemolytic anemia, immune thrombocytopenia, or pure red blood cell aplasia
  • Other active primary malignancy requiring treatment or limits survival to =< 2 years
  • Any major surgery =< 4 weeks prior to registration
  • Any previous chemotherapy or monoclonal antibody treatment for CLL
  • Current use of corticosteroids; NOTE: previous corticosteroids are allowed
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01269385

Locations
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Mayo Clinic Clinical Trials Office    507-538-7623      
Principal Investigator: Clive S. Zent         
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Steven Ansell, M.D. Mayo Clinic
  More Information

No publications provided

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT01269385     History of Changes
Other Study ID Numbers: LS1084, NCI-2010-02329, LS1084, 10-003025
Study First Received: December 23, 2010
Last Updated: February 18, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
Imprime PGG

Additional relevant MeSH terms:
Immune System Diseases
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Antibodies
Antibodies, Monoclonal
Campath 1G
Antibodies, Neoplasm
Rituximab
Alemtuzumab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on April 17, 2014