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B-cell Chronic Lymphocytic LeukemiaPhase 1/2NCT01269385

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

A Phase 1/2 study testing alemtuzumab, rituximab and PGG beta-glucan in people with B-cell Chronic Lymphocytic Leukemia and Refractory Chronic Lymphocytic Leukemia, run by Mayo Clinic at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
alemtuzumab, rituximab and PGG beta-glucan
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
1 siteUnited States
Study dates
Jan 2011to Jun 2015
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
Show all 12Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

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

TERTIARY OBJECTIVES:

  1. 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.

Being tested
alemtuzumab, rituximab, PGG beta-glucan, flow cytometry, laboratory biomarker analysis
Keywords
Imprime PGG
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • alemtuzumabBiological

    Also called anti-CD52 monoclonal antibody, Campath-1H, MoAb CD52, Monoclonal Antibody Campath-1H

    Given subcutaneously

  • rituximabBiological

    Also called IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8

    Given IV

  • PGG beta-glucanDrug

    Also called Imprime PGG

    Given IV

  • flow cytometryOther

    Correlative studies

  • laboratory biomarker analysisOther

    Correlative studies

  • DNA analysisGenetic

    Correlative studies

  • fluorescence in situ hybridizationGenetic

    Also called fluorescence in situ hybridization (FISH)

    Correlative studies

  • polymerase chain reactionGenetic

    Also called PCR

    Correlative studies

  • polymorphism analysisGenetic

    Correlative studies

  • mutation analysisGenetic

    Correlative studies

Study groups in NCT01269385
Study groupRoleWhat they receive
Arm IExperimentalPatients 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD) of PGG Beta Glucan in Combination With Alemtuzumab and Rituximab Assessed by Analyzing the Number of Dose-limiting Toxicity Events (Phase I)

    MTD is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients (at least 2 of a maximum of 6 new patients). A total of 6 patients treated at the MTD will be sufficient to identify common toxicities at the MTD. Three patients will be treated at a given dose level combination for at least 5 weeks to assess toxicity. If dose-limiting toxicity (DLT) is not seen in any of the 3 patients, 3 new patients will be accrued and treated at the next higher dose level. If DLT is seen in 2 or 3 of 3 patients treated at a given dose level, then the next 3 patients will be treated at the next lower dose level, if only 3 patients were enrolled and treated at this lower dose level. We tabulate the number of patients reporting a DLT.

    Measured: First cycle of treatment (35 days)

  2. Proportion of Complete Responses (Dose Level 2)

    The number of patients that demonstrate a Complete Response (CR) during treatment on Dose Level 2 divided by the number of eligible patients starting Dose Level 2 treatment.

    A CR requires all of the following for a period of at least 2 months: Absence of lymphadenopathy by physical examination, no hepatomegaly or splenomegaly, absence of constitutional symptoms, neutrophils >1500/ul, Platelets >100,000/ul, Hemoglobin >11.0 gm/dl, Peripheral blood lymphocytes <4000/uL.

    Measured: 3 months after the completion of treatment, up to 5 years

Secondary outcomes (5)

  1. Overall Response Rate (Dose Level 2)

    Overall response rate was estimated by the total number of patients receiving Dose Level 2 reporting complete responses or partial responses (CR or PR) divided by the total number of evaluable patients that started Dose Level 2 treatment.

    A COMPLETE RESPONSE (CR) requires all of the following for a period of at least 2 months: Absence of lymphadenopathy by physical examination, no hepatomegaly or splenomegaly, absence of constitutional symptoms, neutrophils >1500/ul, Platelets >100,000/ul, Hemoglobin >11.0 gm/dl, Peripheral blood lymphocytes <4000/uL.

    A PARTIAL RESPONSE (PR) requires the patient exhibits at least two of the features: ≥ 50% decrease in peripheral blood lymphocyte count from baseline, ≥ 50% reduction in the sum of the products of the maximal perpendicular diameters of the largest measured node or nodal masses in the right and left cervical, axillary, and inguinal lymph node regions on physical examination.

    Measured: 3 months after the completion of treatment, up to 5 years

  2. Time to Disease Progression

    Time to disease progression is defined as the time from registration to the earliest date of documentation of disease progression. If a patient dies without a documentation of disease progression, the patient will be considered to have had tumor progression at the time of their death unless there is sufficient documented evidence to conclude no progression occurred prior to death. The distribution of time to disease progression will be estimated using the method of Kaplan-Meier.

    Measured: Up to 5 years

  3. Duration of Response for All Evaluable Patients Who Have Achieved an Objective Response

    Duration of response is defined for all evaluable patients who have achieved an objective response as the date at which the patient's objective status is first noted to be either a CR or PR to the earliest date progression is documented. The distribution of duration of response will be estimated using the method of Kaplan-Meier.

    Measured: Up to 5 years

  4. Time to Subsequent Therapy

    Time to subsequent therapy is defined to be the time from the end of active treatment date to the date subsequent therapy is initiated. The distribution of time to subsequent therapy will be estimated using the method of Kaplan-Meier.

    Measured: Up to 5 years

  5. Number of Participants With Grade 3+ Adverse Events

    Adverse events were collected at the end of each cycle according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The number of grade 3+ events at least possibly related to treatment are recorded. For a complete set of all recorded adverse events, please see the Adverse Events section of this report.

    Measured: up to 5 years of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Jan 2011 (estimated)
  2. Study startJan 2011
  3. Primary completionJun 2014
  4. Study completionJun 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01269385
Sponsor's protocol ID
LS1084
Other IDs
NCI-2010-02329, LS1084, 10-003025
Status last verified
Aug 2018
First submitted
23 Dec 2010
Last updated
23 Jun 2020
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing alemtuzumab, rituximab and PGG beta-glucan in people with B-cell Chronic Lymphocytic Leukemia and Refractory Chronic Lymphocytic Leukemia, run by Mayo Clinic at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) of PGG Beta Glucan in Combination With Alemtuzumab and Rituximab Assessed by Analyzing the Number of Dose-limiting Toxicity Events (Phase I) (time frame: First cycle of treatment (35 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01269385.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2020.

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