Ofatumumab-based Induction Chemoimmunotherapy in Previously Untreated Patients With CLL/SLL

• Status: Active, not recruiting
• Trial end date: 2025-12-31
• Target enrollment: 0
• Participant gender: All

Summary

Background:

• Ofatumumab was approved by the U.S. Food and Drug Administration to treat patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have not responded to standard chemotherapy. Ofatumumab is a substance that recognizes specific types of white blood cells called B-lymphocytes, which become cancerous in CLL/SLL. Ofatumumab attaches to a molecule called CD20, which is found on the surface of B-cells, and destroys them. Previous studies have shown that ofatumumab can decrease the number of B-cells in patients with CLL/SLL who have been treated with chemotherapy, but more research is needed to determine it if can also be used to treat patients with previously untreated CLL/SLL.

Objectives:

• To determine a safe and effective dose of ofatumumab, along with chemotherapy, to treat chronic lymphocytic leukemia or small lymphocytic lymphoma.

Eligibility:

• Individuals at least 18 years of age who have been diagnosed with CLL or SLL that has not been treated with chemotherapy.

Design:

• Eligible participants will be screened with a physical exam, blood samples, lymph node and bone marrow biopsies, and imaging studies.

• Participants will be separated into 2 groups: all participants will receive ofatumumab and fludarabine, and some participants will be selected to also receive cyclophosphamide (based on results of certain blood tests).

• Participants will receive the study drugs (ofatumumab and fludarabine, and optional cyclophosphamide) by infusion for a maximum of 6 days, followed by 21 days off drug.

• Participants will have 6 cycles of treatment according to a schedule set by the study doctors, and may have their dose levels adjusted if side effects develop.

• Participants who have disease remaining after 6 cycles will receive additional ofatumumab every 2 months, starting 2 months after the end of the 6th cycle and continuing for a total of 4 doses, before entering the follow-up phase of the trial. Participants who do not have residual disease after 6 cycles will not receive additional therapy, and will immediately enter the follow-up phase of the trial.

• Participants will have a follow-up exam every 2 to 4 months for 2 years after the end of treatment, and then as required by the study doctors for as long as the study remains open. These visits will involve a full medical exam, blood samples, lymph node and bone marrow biopsies, and imaging studies.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Collaborators: GlasoSmithKline; GlaxoSmithKline; University of Virginia
• Treatments: Antibodies, Monoclonal; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Ofatumumab

Criteria

• INCLUSION CRITERIA:

Histologically confirmed CLL or SLL as defined by the following:

• B-lymphocytosis greater than 5000 cells/micro L (may be less than 5000 cells/micro L if lymphadenopathy is present with histologic confirmation of lymph node involvement by SLL).

• Immunophenotypic profile consistent with CLL as demonstrated by flow cytometry

• Appropriate immunophonotype (CD5/19/23+)

• Clonality of lymphocytosis confirmed by flow cytometry

• large lymphocytes less than 55 % of blood lymphocytes

Active disease as defined by at least one of the following:

• Weight loss greater than or equal to10 percent within the previous 6 months

• Extreme fatigue

• Fevers of greater than 100.5 degree F for greater than or equal to 2 weeks without evidence of infection

• Night sweats for more than one month without evidence of infection

• Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia

• Massive or progressive splenomegaly

• Massive nodes or clusters or progressive lymphadenopathy

• Progressive lymphocytosis with an increase of greater than 50% over a 2 month period, or an anticipated doubling time of less than 6 months 0

Measurable disease (defined as two dimensional disease on imaging or quantifiable leukemic disease).

Ages 18 and over.

EXCLUSION CRITERIA:

Prior monoclonal antibody therapy with agents having anti-CLL activity

Prior cytotoxic chemotherapy with agents having anti-CLL activity (Fludarabine, Cyclophosphamide, Bendamustine, Chlorambucil)

Transformed CLL

Active autoimmune hemolytic anemia or thrombocytopenia

Any medical condition that requires the chronic use of corticosteroids

Active or latent Hepatitis B infection

HIV infection

Severe chronic obstructive pulmonary disease, severe cardiac disease, or other uncontrolled medical condition that would, in the opinion of the principal investigator, place the subject at an unreasonable risk of life-threatening adverse events due to chemoimmunotherapy

ECOG performance status 3 or worse

Creatinine greater than or equal to 2 mg/dL or creatinine clearance less than or equal to 30 mL/min

Bilirubin greater than or equal to 2 mg/dL or active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment)

Female patients: Current pregnancy or unwilling to take oral contraceptives or refrain from pregnancy if of childbearing potential or currently breastfeeding. Male patients who are unwilling to follow the contraception requirements described in this protocol.

Psychiatric illness/social situations that would limit the patient s ability to tolerate and/or comply with study requirements.

Unable to understand the investigational nature of the study or give informed consent.