LeukemiaPhase 2NCT00562328
Rituximab, Alemtuzumab, and GM-CSF As First-Line Therapy in Treating Patients With Early-Stage Chronic Lymphocytic Leukemia
A Phase 2 study testing Alemtuzumab, Rituximab and Sargramostim in people with Leukemia, run by Mayo Clinic at 2 sites in United States.
Trial summary
RATIONALE: Monoclonal antibodies, such as rituximab and alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Leukemia
- What is being tested?
- Alemtuzumab, Rituximab and Sargramostim
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2008to 18 Dec 2014
- Phase
- Phase 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 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Diagnosis of chronic lymphocytic leukemia (CLL) meeting the following criteria:
- Minimum threshold peripheral blood lymphocyte count 5 x 10^9/L
- Monoclonality (light chain exclusion) of B lymphocytes detected by immunophenotyping (CD19-positive), demonstrating ≥ 3 of the following characteristics:
- CD5-positive
- CD23-positive
- Dim surface light chain expression
- Dim surface CD20 expression
- Negative for IGH/CCND1 translocation AND/OR immunostaining is negative for cyclin D1 expression by fluorescent in-situ hybridization (FISH) analysis
- Rai stage 0, I, or II disease that does not meet standard NCI-Working Group criteria for treatment of CLL
- Poor prognosis as defined by ≥ 1 of the following factors:
- Unmutated IgVH mutation status AND CD38 expression (i.e., ≥ 30% cells positive on flow cytometry)
- Unmutated IgVH mutation status AND ZAP-70 expression (i.e., ≥ 20% cells positive on flow cytometry)
- VH3-21 gene segment use irrespective of mutation status AND CD38 expression (≥ 30% cells positive on flow cytometry)
- VH3-21 gene segment use irrespective of mutation status AND ZAP-70 expression (≥ 20% cells positive on flow cytometry)
- 11q-negative*
- 17p-negative* NOTE: *Determination of IgVH mutation status is not required in patients whose eligibility is based on 17p13- or 11q22- deletions
PATIENT CHARACTERISTICS:
- ECOG performance status 0- 2
- Creatinine ≤ 1.5 times upper limit of normal (ULN)
- Total bilirubin ≤ 3.0 times ULN OR direct bilirubin ≤ 1.5 ULN
- AST ≤ 3.0 times ULN (unless due to hemolysis or CLL)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must practice effective contraception
- Willing to provide mandatory blood samples (for patients at the Mayo Clinic in Rochester only) for research studies as required by the protocol
- No comorbid conditions, including any of the following:
- New York Heart Association Class III or IV heart disease
- Myocardial infarction within the past month
- Uncontrolled infection
- HIV infection or AIDS
- Serological evidence of active hepatitis B infection (i.e., serum antigen or e-antigen positivity) or positive hepatitis C serology
- No other active primary malignancy requiring treatment or limiting survival to ≤ 2 years
- No active autoimmune hemolytic anemia, immune thrombocytopenia, or pure red blood cell aplasia
PRIOR CONCURRENT THERAPY:
- More than 4 weeks since prior major surgery
- No prior chemotherapy or monoclonal antibody treatment for CLL
- No concurrent corticosteroids
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Mayo Clinic Cancer Center
Rochester, Minnesota, 55905
Mayo Clinic Scottsdale
Scottsdale, Arizona, 85259-5499
About this study
Official title: Antibody Therapy With Alemtuzumab, Rituximab and GM-CSF for Initial Treatment of High Risk Chronic Lymphocytic Leukemia
RATIONALE: Monoclonal antibodies, such as rituximab and alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Colony-stimulating factors, such as GM-CSF, may increase the number of immune cells found in bone marrow or peripheral blood. Giving monoclonal antibody therapy together with GM-CSF may be an effective treatment for early-stage chronic lymphocytic leukemia.
PURPOSE: This phase II trial is studying the side effects of giving rituximab and alemtuzumab together with GM-CSF and to see how well it works in treating patients with early-stage chronic lymphocytic leukemia.
Read the detailed description
OBJECTIVES:
Primary
- To assess the rate of complete and overall response in patients with high-risk, early-stage, chronic lymphocytic leukemia (CLL) treated with alemtuzumab, rituximab, and sargramostim (GM-CSF).
- To monitor and assess toxicity of this regimen in these patients through clinical evaluation and serial monitoring of cytomegalovirus antigenemia by polymerase chain reaction (PCR).
Secondary
- To determine the overall and progression-free survival, time to response, time to next treatment, and duration of response in patients treated with this regimen.
- To assess the correlation between individual prognostic markers (i.e., 17p-, 11q-, unmutated VH gene, use of VH3-21, ZAP70+, CD38+) and clinical outcome.
Correlative Studies
- To assess response in these patients using an expanded definition of response, including minimal residual disease (MRD) by sensitive flow cytometry in patients in complete clinical remission.
- To assess MRD status of responding patients using sensitive flow cytometry and molecular assays (i.e., spectral karyotype analysis of CLL cells) before treatment and at relapse to identify subpopulations that could contribute to disease resistance and relapse.
- To detail the in vivo effect of this regimen on critical aspects of the immune system in CLL.
- To determine if GM-CSF, β-glucan, and CpG7909 can increase antibody dependent cellular cytotoxicity to improve efficacy against CLL cells and clinical response to treatment.
OUTLINE: Patients receive rituximab IV over 30 minutes on day 3 of weeks 2-5, alemtuzumab subcutaneously (SC) on days 3, 4, and 5 in week 1 and on days 1, 3, and 5 in weeks 2-5, and sargramostim SC on days 1, 3, and 5 in weeks 1-6. Treatment continues in the absence of disease progression or unacceptable toxicity.
Patients undergo blood sample collection for measurement of serum cytomegalovirus DNA copy number by polymerase chain reaction at baseline, weekly during treatment, and monthly for the 6 months after completion of treatment. Patients also undergo bone marrow biopsy and aspirate at two months and then again at 12 months (if in complete remission). Blood samples are collected periodically during study for evaluation of prognostic biomarkers (i.e., 11q-, 17p-, unmutated IgVH gene, VH3-21 gene segment use, and CD38 and ZAP-70 expression) by fluorescent in situ hybridization (FISH) and for immunophenotyping by flow cytometry. Blood samples are collected from patients at the Mayo Clinic Rochester site at baseline and periodically during study for immunological and other correlative studies, including minimal residual disease (in responding patients only).
After completion of study therapy, patients are followed periodically for up to 5 years.
- Conditions
- Leukemia
- Being tested
- Alemtuzumab, Rituximab, Sargramostim
- Keywords
- stage 0 chronic lymphocytic leukemia, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia
- Medical subject headings
- Leukemia, 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
Week 1 (dose escalation):
Day 3: 3mg subcutaneously; Day 4: 10mg subcutaneously; Day 5 30mg subcutaneously
Weeks 2-5:
30mg subcutaneously three times a week.
RituximabBiological
Weeks 2-5:
375 mg/m^2 by IV once weekly
SargramostimBiological
Also called GM-CSF
Week 1-6:
250 mcg subcutaneously three time as week
| Study group | Role | What they receive |
|---|---|---|
| Alemtuzumab + Rituximab + GM-CSF | Experimental | Alemtuzumab + Rituximab + GM-CSF Receives: Biological: Alemtuzumab; Biological: Rituximab; Biological: Sargramostim |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Confirmed Responses (Complete or Partial Response Noted as the Objective Status for a Duration of at Least 2 Months) at 6 Months
Response, as defined by the National Cancer Institute Working Group (NCIWG), requires the following for a period of at least 2 months:
- CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate \& biopsy
- PR: 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver/spleen size, presence/absence of constitutional symptoms; plus ≥1 of the following: ≥1500/μL polymorphonuclear leukocytes, >100,000/μL platelets, >11.0 g/dL hemoglobin or 50% improvement for these parameters without transfusions
Measured: 6 months
Secondary outcomes (4)
Progression Free Survival
Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to the standard NCI-WG96 criteria. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
Measured: Time from registration to progression (up to 5 years)
Duration of Response
Duration of response (DOR) is defined as the time from documentation of response (CR or PR) to disease progression. The median DOR with 95% CI was estimated using the Kaplan Meier method.Response, as defined by the National Cancer Institute Working Group (NCIWG), requires the following for a period of at least 2 months:
- CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate \& biopsy
- PR: 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver/spleen size, presence/absence of constitutional symptoms; plus ≥1 of the following: ≥1500/μL polymorphonuclear leukocytes, >100,000/μL platelets, >11.0 g/dL hemoglobin or 50% improvement for these parameters without transfusions
Measured: time from start of response to progression (up to 5 years)
Time to Next Treatment
Time to next treatment was defined as the time from end of active (protocol) treatment to the start of subsequent treatment. The median and 95% CI was estimated using the Kaplan Meier method.
Measured: time from end of protocol treatment to subsequent treatment (up to 5 years)
Overall Survival
Overall Survival (OS) was defined as the time from registration to death of any cause. Participants were followed for a maximum of 5 years from registration. The median OS with 95% CI was estimated using the Kaplan Meier method.
Measured: Time from registration to death (up to 5 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2007 (estimated)
- Study startJan 2008
- Primary completion5 Feb 2010
- Study completion18 Dec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Clive S. Zent, MD, Study chair, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00562328
- Sponsor's protocol ID
- CDR0000574754
- Other IDs
- P30CA015083, MC0785, U4449s, 001.0888, 07-002087
- Status last verified
- May 2017
- First submitted
- 21 Nov 2007
- Last updated
- 8 Apr 2020
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Zent CS, Wu W, Bowen DA, Hanson CA, Pettinger AM, Shanafelt TD, Kay NE, Leis JF, Call TG. Addition of granulocyte macrophage colony stimulating factor does not improve response to early treatment of high-risk chronic lymphocytic leukemia with alemtuzumab and rituximab. Leuk Lymphoma. 2013 Mar;54(3):476-82. doi: 10.3109/10428194.2012.717276. Epub 2012 Aug 22.
PubMed 22853816
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Antibody Therapy With Alemtuzumab, Rituximab and GM-CSF for Initial Treatment of High Risk Chronic Lymphocytic Leukemia
- ClinicalTrials.gov ID
- NCT00562328
- Acronym / sponsor ID
- CDR0000574754
- Conditions
- Leukemia
- Keywords
- stage 0 chronic lymphocytic leukemia, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jan 2008 (actual)
- Primary completion
- 5 Feb 2010 (actual)
- Study completion
- 18 Dec 2014 (actual)
- First posted
- 22 Nov 2007 (estimated)
- Results
- Posted 8 May 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Monoclonal antibodies, such as rituximab and alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Colony-stimulating factors, such as GM-CSF, may increase the number of immune cells found in bone marrow or peripheral blood. Giving monoclonal antibody therapy together with GM-CSF may be an effective treatment for early-stage chronic lymphocytic leukemia.
PURPOSE: This phase II trial is studying the side effects of giving rituximab and alemtuzumab together with GM-CSF and to see how well it works in treating patients with early-stage chronic lymphocytic leukemia.
Detailed description
OBJECTIVES:
Primary
- To assess the rate of complete and overall response in patients with high-risk, early-stage, chronic lymphocytic leukemia (CLL) treated with alemtuzumab, rituximab, and sargramostim (GM-CSF).
- To monitor and assess toxicity of this regimen in these patients through clinical evaluation and serial monitoring of cytomegalovirus antigenemia by polymerase chain reaction (PCR).
Secondary
- To determine the overall and progression-free survival, time to response, time to next treatment, and duration of response in patients treated with this regimen.
- To assess the correlation between individual prognostic markers (i.e., 17p-, 11q-, unmutated VH gene, use of VH3-21, ZAP70+, CD38+) and clinical outcome.
Correlative Studies
- To assess response in these patients using an expanded definition of response, including minimal residual disease (MRD) by sensitive flow cytometry in patients in complete clinical remission.
- To assess MRD status of responding patients using sensitive flow cytometry and molecular assays (i.e., spectral karyotype analysis of CLL cells) before treatment and at relapse to identify subpopulations that could contribute to disease resistance and relapse.
- To detail the in vivo effect of this regimen on critical aspects of the immune system in CLL.
- To determine if GM-CSF, β-glucan, and CpG7909 can increase antibody dependent cellular cytotoxicity to improve efficacy against CLL cells and clinical response to treatment.
OUTLINE: Patients receive rituximab IV over 30 minutes on day 3 of weeks 2-5, alemtuzumab subcutaneously (SC) on days 3, 4, and 5 in week 1 and on days 1, 3, and 5 in weeks 2-5, and sargramostim SC on days 1, 3, and 5 in weeks 1-6. Treatment continues in the absence of disease progression or unacceptable toxicity.
Patients undergo blood sample collection for measurement of serum cytomegalovirus DNA copy number by polymerase chain reaction at baseline, weekly during treatment, and monthly for the 6 months after completion of treatment. Patients also undergo bone marrow biopsy and aspirate at two months and then again at 12 months (if in complete remission). Blood samples are collected periodically during study for evaluation of prognostic biomarkers (i.e., 11q-, 17p-, unmutated IgVH gene, VH3-21 gene segment use, and CD38 and ZAP-70 expression) by fluorescent in situ hybridization (FISH) and for immunophenotyping by flow cytometry. Blood samples are collected from patients at the Mayo Clinic Rochester site at baseline and periodically during study for immunological and other correlative studies, including minimal residual disease (in responding patients only).
After completion of study therapy, patients are followed periodically for up to 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Alemtuzumab + Rituximab + GM-CSF | Experimental | Biological: Alemtuzumab, Biological: Rituximab, Biological: SargramostimAlemtuzumab + Rituximab + GM-CSF |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlemtuzumabWeek 1 (dose escalation): Day 3: 3mg subcutaneously; Day 4: 10mg subcutaneously; Day 5 30mg subcutaneously Weeks 2-5: 30mg subcutaneously three times a week. | Biological | Alemtuzumab + Rituximab + GM-CSF |
| RituximabWeeks 2-5: 375 mg/m^2 by IV once weekly | Biological | Alemtuzumab + Rituximab + GM-CSF |
| SargramostimAlso: GM-CSFWeek 1-6: 250 mcg subcutaneously three time as week | Biological | Alemtuzumab + Rituximab + GM-CSF |
Primary outcome
Number of Confirmed Responses (Complete or Partial Response Noted as the Objective Status for a Duration of at Least 2 Months) at 6 Months
Time frame: 6 months
Response, as defined by the National Cancer Institute Working Group (NCIWG), requires the following for a period of at least 2 months: * CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate \& biopsy * PR: 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver/spleen size, presence/absence of constitutional symptoms; plus ≥1 of the following: ≥1500/μL polymorphonuclear leukocytes, >100,000/μL platelets, >11.0 g/dL hemoglobin or 50% improvement for these parameters without transfusions
4 secondary outcomes
Progression Free Survival
Time frame: Time from registration to progression (up to 5 years)
Duration of Response
Time frame: time from start of response to progression (up to 5 years)
Time to Next Treatment
Time frame: time from end of protocol treatment to subsequent treatment (up to 5 years)
Overall Survival
Time frame: Time from registration to death (up to 5 years)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22853816Zent CS, Wu W, Bowen DA, Hanson CA, Pettinger AM, Shanafelt TD, Kay NE, Leis JF, Call TG. Addition of granulocyte macrophage colony stimulating factor does not improve response to early treatment of high-risk chronic lymphocytic leukemia with alemtuzumab and rituximab. Leuk Lymphoma. 2013 Mar;54(3):476-82. doi: 10.3109/10428194.2012.717276. Epub 2012 Aug 22.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clive S. Zent, MD study chair
Mayo Clinic
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Alemtuzumab, Rituximab and Sargramostim in people with Leukemia, run by Mayo Clinic at 2 sites 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?
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 8 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 phase mean?
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 8 May 2012). 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?
Number of Confirmed Responses (Complete or Partial Response Noted as the Objective Status for a Duration of at Least 2 Months) at 6 Months (time frame: 6 months). 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 NCT00562328, which also lists 1 linked publication.
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 8 Apr 2020.