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

NCT01145209 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 10014110-H-0141
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Small Lymphocytic Lymphoma; CLL (Chronic Lymphocytic Leukemia)

Keywords

Arzerra; Chemoimmunotherapy; SLL; Monoclonal Antibody Therapy; CLL; Ofatumumab

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival Rate 2 Years After Initiation of Induction Therapy

  Death or disease progression defined by the 2008 IWCLL guideline as follows; * Greater than or equal to 50% increase in the SPD of at least 2 lymph nodes (at least one node must be greater than or equal to 2 cm); appearance of any new lymph nodes on physical examination or imaging * Greater than or equal to 50% increase in the size of the liver and/or spleen as determined by measurement below the respective costal margin or CT scan or appearance of palpable hepatomegaly or splenomegaly, which was not previously present * Greater than or equal to 50% increase in the absolute number of circulating lymphocytes to at least 5000/ul * Transformation to a more aggressive histology * Occurrence of any cytopenia attributable to CLL. After treatment: the progression of any cytopenia (unrelated to autoimmune cytopenia), as documented by a decrease of Hb levels by more than 20 g/L (2 g/dL) or to less than 100 g/L (10 g/dL), or by a decrease of platelet counts by more than 50% or to les

  2 years

Secondary Outcomes (7)

• Number of Grade 3 and 4 Treatment Related Adverse Events

  2 years

• Participants With Minimal Residual Disease (MRD) Negativity

  2 years

• Participants With MRD Negativity at the Completion of Consolidation Immunotherapy Who Failed to Achieve MRD Negativity

  2 years

• Participants With Complete Response Rates Following Induction Chemoimmunotherapy.

  2 years

• Participants Overall Response Rates Following Induction Chemoimmunotherapy.

  2 years

Study Arms (2)

FO Arm (fludarabine and ofatumumab)

EXPERIMENTAL

For patients with non-high risk FISH changes

Drug: Fludarabine Phosphate; Biological: Ofatumumab

FCO Arm (fludarabine, cyclophosphamide, and ofatumumab)

EXPERIMENTAL

For patients with high risk FISH changes

Drug: Fludarabine Phosphate; Biological: Ofatumumab; Drug: Cyclophosphamide

Interventions

Fludarabine Phosphate DRUG

Given IV

Also known as: Fludara

FCO Arm (fludarabine, cyclophosphamide, and ofatumumab); FO Arm (fludarabine and ofatumumab)

Ofatumumab BIOLOGICAL

Given IV

Also known as: Arzerra

FCO Arm (fludarabine, cyclophosphamide, and ofatumumab); FO Arm (fludarabine and ofatumumab)

Cyclophosphamide DRUG

Given IV

Also known as: Cytoxan, Neosar

FCO Arm (fludarabine, cyclophosphamide, and ofatumumab)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead
• University of Virginia: collaborator
• GlaxoSmithKline: collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (2)

• Ahn I, Farooqui M, Lee YS, Marti G, Soto S, Tian X, Stetler-Stevenson M, Yuan CM, Maric I, Wiestner A. Risk-Adapted Induction and Maintenance with Ofatumumab in Previously Untreated Patients with Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL). Blood 2015 126(23):1750-1750.

  BACKGROUND

• Desai S, Mo C, Gaglione EM, Yuan CM, Stetler-Stevenson M, Tian X, Maric I, Wake L, Farooqui MZ, Drinkwater DC, Soto S, Valdez J, Hughes TE, Nierman P, Lotter J, Marti GE, Pleyer C, Sun C, Superata J, Nichols C, Herman SEM, Lindorfer MA, Taylor RP, Wiestner A, Ahn IE. Risk-adapted, ofatumumab-based chemoimmunotherapy and consolidation in treatment-naive chronic lymphocytic leukemia: a phase 2 study. Leuk Lymphoma. 2021 Aug;62(8):1816-1827. doi: 10.1080/10428194.2021.1888379. Epub 2021 Mar 2.

  PMID: 33653216 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, B-Cell

Interventions

fludarabine phosphate; ofatumumab; Cyclophosphamide

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Wiestner, Adrian MD, PhD
• Organization: National Heart Lung and Blood Institute

wiestnea@nhlbi.nih.gov

+1.301.594.6855

Study Officials

• Inhye Ahn, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2010
• First Posted: June 16, 2010
• Study Start: July 1, 2010
• Primary Completion: October 31, 2017
• Study Completion: September 15, 2023
• Last Updated: November 28, 2023
• Results First Posted: September 17, 2019

Record last verified: 2023-11

Locations

US (1)