Know Cancer

or
forgot password

Early Treatment of High Risk Chronic Lymphocytic Leukemia With Alemtuzumab, Rituximab, and PGG Beta-Glucan: A Phase I/II Trial


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
B-cell Chronic Lymphocytic Leukemia, Refractory Chronic Lymphocytic Leukemia, Stage 0 Chronic Lymphocytic Leukemia, Stage I Chronic Lymphocytic Leukemia, Stage II Chronic Lymphocytic Leukemia

Thank you

Trial Information

Early Treatment of High Risk Chronic Lymphocytic Leukemia With Alemtuzumab, Rituximab, and PGG Beta-Glucan: A Phase I/II Trial


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.


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the maximum tolerated dose (MTD) of PGG beta glucan in combination with alemtuzumab and rituximab (Phase I)

Outcome Time Frame:

At least 5 weeks

Safety Issue:

Yes

Principal Investigator

Clive Zent, M.D.

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic

Authority:

United States: Food and Drug Administration

Study ID:

LS1084

NCT ID:

NCT01269385

Start Date:

January 2011

Completion Date:

Related Keywords:

  • B-cell Chronic Lymphocytic Leukemia
  • Refractory Chronic Lymphocytic Leukemia
  • Stage 0 Chronic Lymphocytic Leukemia
  • Stage I Chronic Lymphocytic Leukemia
  • Stage II Chronic Lymphocytic Leukemia
  • Imprime PGG
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid

Name

Location

Mayo ClinicRochester, Minnesota  55905