Weekly Subcutaneous Alemtuzumab and Rituximab for Relapsed CLL

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
Jennifer R. Brown, MD, PhD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00330252
First received: May 25, 2006
Last updated: April 24, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Chronic Lymphocytic Leukemia
Drug: Rituximab
Drug: Alemtuzumab
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Weekly Subcutaneous Alemtuzumab and Rituximab for Relapsed CLL

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Maximum tolerated dose of alemtuzumab given once weekly [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Response rate of combined rituximab and subcutaneous alemtuzumab (complete or partial response) [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • 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 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • 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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 29
Study Start Date: May 2006
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Alemtuzumab & Rituximab

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)

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

Drug: Rituximab
Given intravenously on day 1 of every week for eight weeks (or 16 weeks)
Drug: Alemtuzumab
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).

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.

  Eligibility

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

Inclusion Criteria:

  • 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
  • WHO Performance status <= 2
  • Subject has provided written informed consent.
  • Expected survival > 3 months

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00330252

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Dana-Farber Cancer Institute
Genzyme, a Sanofi Company
Investigators
Principal Investigator: Jennifer R Brown, MD, PhD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Jennifer R. Brown, MD, PhD, Assistant Professor of Medicine, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00330252     History of Changes
Other Study ID Numbers: 05-404
Study First Received: May 25, 2006
Last Updated: April 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
Chronic Lymphocytic Leukemia
Relapsed Chronic Lymphocytic Leukemia
Alemtuzumab
Campath
Rituximab
Rituxan

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

ClinicalTrials.gov processed this record on September 18, 2014