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Chronic Lymphocytic LeukemiaPhase 1NCT00330252

Weekly Subcutaneous Alemtuzumab and Rituximab for Relapsed CLL

A Phase 1 study testing Rituximab and Alemtuzumab in people with Chronic Lymphocytic Leukemia, run by Dana-Farber Cancer Institute at 2 sites 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

The purpose of this study is to determine whether the combination of alemtuzumab and rituximab is safe and effective in treating patients with relapsed Chronic Lymphocytic Leukemia (CLL) and to determine whether alemtuzumab can be given as a single weekly subcutaneous dose, together with rituximab. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Lymphocytic Leukemia
What is being tested?
Rituximab and Alemtuzumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
2 sitesUnited States
Study dates
May 2006to Jan 2014
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Subjects must be diagnosed with B-CLL / SLL (B-chronic lymphocytic leukemia / small lymphocytic lymphoma) based on the standard histologic and immunophenotypic criteria described in the WHO classification of lymphoid malignancies, including immunophenotypic confirmation that the tumor cells co-express B cell antigens CD19 / 20 and CD5. Mantle cell lymphoma should be excluded based on positive staining of the tumor cells for CD23, or the absence of staining of the tumor cells for cyclin D1 or the absence of t(11;14).
  • The above diagnosis must be confirmed at Brigham \& Women's Hospital or Dana-Farber Cancer Institute.
  • Subjects must have relapsed after at least one prior fludarabine-containing regimen and require treatment based on NCI-WG criteria (Appendix A).
  • Subjects must have measurable disease (lymphocytosis > 5,000 / ml, or palpable lymphadenopathy or CT measurable lymphadenopathy > 1.5 cm, or bone marrow involvement >30%).
  • Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for six months after completion of treatment.
  • Age >= 18
Show all 9Show fewer
  • WHO Performance status <= 2
  • Subject has provided written informed consent.
  • Expected survival > 3 months

Who cannot join

  • History of HIV
  • Active infection uncontrolled by appropriate antibacterial, antiviral or antifungal therapy
  • Known CNS involvement with CLL
  • Pregnant (a negative serum pregnancy test should be performed for all women of childbearing potential within 7 days of treatment) or currently lactating women
  • Prior anti-neoplastic therapy within the last three weeks
  • Patients will NOT be excluded because they have received prior rituximab or alemtuzumab

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

Other trials in United States

About this study

The purpose of this study is to determine whether the combination of alemtuzumab and rituximab is safe and effective in treating patients with relapsed Chronic Lymphocytic Leukemia (CLL) and to determine whether alemtuzumab can be given as a single weekly subcutaneous dose, together with rituximab.

Read the detailed description

This study proposes to combine alemtuzumab, which effectively treats peripheral blood and bone marrow disease in CLL, with rituximab, which has activity in lymph node disease, in a streamlined and convenient administration schedule. Preclinical data support synergistic interaction of the two. The primary objectives are (1) to determine the overall and complete response (CR) rate in patients with relapsed CLL and to determine the safety of the combination, and (2) the safety of higher doses of alemtuzumab at less frequent intervals. Secondary objectives are (1) to describe the duration of response, progression-free survival, and overall survival in patients not proceeding to allo transplant, (2) to determine the improvement in overall and complete response associated with administration of a 2nd eight week course of therapy, and (3) to assess minimal residual disease in certain patients and to correlate those results with survival. If at least 16 responses are observed among 35 patients, then the treatment will be considered promising.

The development of antibody therapies has held promise for CLL, since CLL therapies have been palliative, with no established therapy shown to improve survival. Studies have suggested that in contrast to what is seen with fludarabine and alkylating agents, response rates to alemtuzumab are maintained in CLL subjects with P53 mutations. Tolerability of rituximab and its major activity in nodes make it an attractive candidate for combination with alemtuzumab.

This is a single center (DF/HCC), single arm, multi cohort, phase I study, with treatment on an outpatient basis. If the initial alemtuzumab dose of 30 mg sc d1, 3,and 5 is tolerated, there will be dose escalations in cohorts of 3, up to 90 mg d1 per week. Following determination of a maximum tolerated dose, accrual of all remaining patients will occur at that dose. Subjects will be restaged after 8 weeks of therapy, and may proceed to transplant. If deriving benefit, but not in CR, subjects may receive another 8 weeks of therapy.

Being tested
Rituximab, Alemtuzumab
Keywords
Chronic Lymphocytic Leukemia, Relapsed Chronic Lymphocytic Leukemia, Alemtuzumab, Campath, Rituximab, Rituxan
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.

  • RituximabDrug

    Given intravenously on day 1 of every week for eight weeks (or 16 weeks)

  • AlemtuzumabDrug

    Drug: Alemtuzumab Dosage will vary during Phase I of trial: Given intravenously on days 1, 3, and 5 for weeks one and two, on days 1 and 4 for weeks three and four and on day 1 for weeks five through eight. Participants may receive either one eight-week course of treatment or two eight-week courses of treatment (16 weeks).

Study groups in NCT00330252
Study groupRoleWhat they receive
Alemtuzumab & RituximabExperimentalAlemtuzumab Dosage will vary during Phase I of trial: Given intravenously on days 1, 3, and 5 for weeks one and two, on days 1 and 4 for weeks three and four and on day 1 for weeks five through eight. Participants may receive either one eight-week course of treatment or two eight-week courses of treatment (16 weeks) Rituximab- Given intravenously on day 1 of every week for eight weeks (or 16 weeks)
Receives: Drug: Rituximab; Drug: Alemtuzumab

What is being measured

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

  1. Maximum tolerated dose of alemtuzumab given once weekly

    Measured: 2 years

  2. Response rate of combined rituximab and subcutaneous alemtuzumab (complete or partial response)

    Measured: 2 years

Secondary outcomes (4)

  1. Dose limiting toxicities defined as non-hematologic toxicity of grade 3 or greater or irreversible grade 2 renal, neurologic or cardiac toxicity or infectious toxicities if grade 4 or greater

    Measured: 2 years

  2. Dose limiting toxicities defined as hematologic toxicities of grade 3 or greater neutropenia or thrombocytopenia for greater than 2 weeks OR ANC < 250 or platelets < 20,000

    Measured: 2 years

  3. Response rate as measured by Chest/abdominal/pelvic (+/- neck) CT 4 to 8 weeks following conclusion of 8 Weeks of therapy or at time of study withdrawal

    Measured: 2 years

  4. Response rate as measured by physical exam of lymph nodes at 4 to 8 weeks following conclusion of 8 Weeks of therapy or at time of study withdrawal, then every 3 months until disease progression

    Measured: 2 years

Timeline

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

  1. First posted26 May 2006 (estimated)
  2. Study startMay 2006
  3. Primary completionJan 2013
  4. Study completionJan 2014

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00330252
Sponsor's protocol ID
05-404
Status last verified
May 2016
First submitted
25 May 2006
Last updated
13 May 2016
Results posted
No
Data monitoring committee
Yes

Publications

  • Brown JR, Messmer B, Werner L, Davids MS, Mikler E, Supko JG, Fisher DC, LaCasce AS, Armand P, Jacobsen E, Dalton V, Tesar B, Fernandes SM, McDonough S, Ritz J, Rassenti L, Kipps TJ, Neuberg D, Freedman AS. A phase I study of escalated dose subcutaneous alemtuzumab given weekly with rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma. Haematologica. 2013 Jun;98(6):964-70. doi: 10.3324/haematol.2013.086207. Epub 2013 May 3.

    PubMed 23645694

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Rituximab and Alemtuzumab in people with Chronic Lymphocytic Leukemia, run by Dana-Farber Cancer Institute 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?

The sponsor lists 9 inclusion and 6 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 13 May 2016. 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 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.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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 of alemtuzumab given once weekly (time frame: 2 years). 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 NCT00330252, 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 13 May 2016.

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