Ofatumumab and High-dose Methylprednisolone in Patients With Chronic Lymphocytic Leukemia (CLL)

NCT01191190 | Completed Phase 2 Results DMC

• 1 other identifier: 100429
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

Brief Summary

Patients who have relapsed/refractory CLL and require therapy as per iwCLL guidelines will be eligible. Subjects will receive a treatment with ofatumumab and HDMP for three consecutive 4 week cycles. The primary endpoint is to determine the complete response (CR) to therapy and the secondary endpoints will assess the safety and tolerability of the regimen, the impact of the treatment on progression free, treatment free, overall survival, and pharmacokinetics of ofatumumab. Patients will receive allopurinol for tumor-lysis prophylaxis and antimicrobial prophylaxis.

Conditions

CLL

Keywords

Leukemia; Chronic leukemia; Chronic Lymphocytic Leukemia; Relapsed; Refractory

Outcome Measures

Primary Outcomes (1)

• IwCLL-WG Defined Complete Response (CR)

  Responses were assessed two months after completion of therapy. Criteria for complete remission is assessed with: a bone marrow biopsy and repeat CT scan (abdominal, chest and pelvis if initial was abnormal) to confirm iwCLL-WG defined CR. iwCLL-WG Complete Response is defined as: * Peripheral blood lymphocytes (evaluated by blood and differential count) below 4 x 109/L (4000/L). * Absence of lymphadenopathy (\>1.5 cm)of physical exam; AND * No hepatomegaly and splenomegaly on physical exam; AND * Absence of constitutional symptoms; AND * Normal complete blood count as exhibited by neutrophils ≥ 1,500/μl, platelets \> 100,000/μl, hemoglobin \> 11.0g/dL (non-transfused), and lymphocyte count \< 5,000/μl; AND * Bone marrow aspirate and biopsy must be normocellular for age with \<30% of nucleated cells being lymphocytes. Lymphoid nodules must be absent

  2 months

Secondary Outcomes (9)

• IwCLL-WG Defined Overall Response Rate (ORR)

  2 months

• IwCLL-WG Defined Nodular Partial Response (PR)

  2 months

• IwCLL-WG Defined Partial Response (PR)

  2 months

• IwCLL-WG Defined Stable Disease (SD)

  2 months

• IwCLL-WG Defined Progressive Disease (PD)

  2 months

Study Arms (1)

Ofatumumab/HDMP

EXPERIMENTAL

High dose methylprednisolone sodium succinate (HDMP) at 1gm/m2 daily as infusion for 3 consecutive days every cycle. Ofatumumab 300mg administered Day1 of cycle 1 followed by 12 doses of 1000mg administered. Each patient may receive 3 cycles of treatment in the absence of progressive disease or significant toxicity.

Drug: Ofatumumab/HDMP

Interventions

Ofatumumab/HDMP DRUG

High dose methylprednisolone sodium succinate (HDMP) at 1gm/m2 daily as infusion for 3 consecutive days every cycle. Ofatumumab 300mg administered Day1 of cycle 1 followed by 12 doses of 1000mg administered based on specific schedule. Each patient will receive a maximum of 3 cycles (one cycle is 28 days)

Also known as: Arzerra, HuMax-CD20

Ofatumumab/HDMP

Eligibility Criteria

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

You may qualify if:

• Previously treated patients with a diagnosis of CLL
• Previous treatment with any monoclonal antibody or chemotherapy regardless of response as defined by the iwCLL Working Group Guidelines as evidenced by:
• progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia
• massive (i.e. at least 6cm below the left costal margin) or progressive or symptomatic splenomegaly
• massive nodes (i.e. at least 10cm in longest diameter) or progressive or symptomatic lymphadenopathy.
• progressive lymphocytosis with an increase of more than 50% over a 2-month period or lymphocyte doubling time (LDT) of less than 6 months.
• autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy (See Section 10.2)
• Constitutional symptoms, defined as any one or more of the following disease-related symptoms or signs: unintentional weight loss of 10% or more within the previous 6 months significant fatigue (i.e. ECOG PS 2 or worse, inability to work or perform usual activities), fevers higher than 100.5ºF or 38.0ºC for 2 or more weeks without other evidence of infection, night sweats for more than 1 month without evidence of infection
• Subjects must be 18 years of age or older, male or female.
• ECOG performance status of 0-2.
• Subjects must be able to give informed consent.
• Females of child bearing potential(FCBP)† must have a negative serum or urine pregnancy test within 10 - 14 days prior to and again within 24 hours of starting treatment and agree to use a medically accepted contraceptive method for the duration of this study.

You may not qualify if:

• Hepatitis BsAg positive, Hepatitis BcAb positive, and Hepatitis C positive patients.
• Known HIV positive patients.
• Diabetics.
• Patients with uncontrolled Autoimmune Hemolytic Anemia (AIHA) or autoimmune thrombocytopenia (ITP).
• Screening laboratory values within these ranges: platelets \<50 x 109/L, neutrophils \<1.0 x 109/L, creatinine \>2.0 times upper normal limit,total bilirubin \>1.5 times upper normal limit (unless a known history of Gilbert's disease), ALT \>2.5 times upper normal limit (unless due to disease involvement of liver), alkaline phosphatase \>2.5 times upper normal limit (unless due to disease involvement of the liver or bone marrow)
• Inability to provide informed consent.
• Concurrent malignancy (excluding basal and squamous cell skin cancers).
• Active fungal, bacterial, and/or viral infection.
• History of peptic ulcer disease resulting in GI bleeding within the last 6 months.
• Untreated metabolic disorders such as hypothyroidism and Cushing's disease.
• History of steroid-induced psychosis.
• Estimated life expectancy of less than 3 months by the investigator's best clinical judgment.
• Serious medical condition that would render the subject medically unstable.
• Women who are pregnant or breast-feeding.
• History of Pancreatitis.

Sponsors & Collaborators

• Januario Castro, M.D.: lead
• GlaxoSmithKline: collaborator

Study Sites (2)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

University of California San Diego, Moores Cancer Center

La Jolla, California, 92093, United States

Location

Related Publications (2)

• Castro JE, James DF, Sandoval-Sus JD, Jain S, Bole J, Rassenti L, Kipps TJ. Rituximab in combination with high-dose methylprednisolone for the treatment of chronic lymphocytic leukemia. Leukemia. 2009 Oct;23(10):1779-89. doi: 10.1038/leu.2009.133. Epub 2009 Aug 20.

  PMID: 19693094 BACKGROUND

• Castro JE, Sandoval-Sus JD, Bole J, Rassenti L, Kipps TJ. Rituximab in combination with high-dose methylprednisolone for the treatment of fludarabine refractory high-risk chronic lymphocytic leukemia. Leukemia. 2008 Nov;22(11):2048-53. doi: 10.1038/leu.2008.214. Epub 2008 Aug 28.

  PMID: 18754025 BACKGROUND

Related Links

• Moore's UCSD Cancer Center
• Website for the Chronic Lymphocytic Leukemia Research Consortium

MeSH Terms

Conditions

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

Interventions

ofatumumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Januario E Castro, MD
• Organization: University of California, San Diego

jecastro@ucsd.edu

(858) 822-6600

Study Officials

• Januario Castro, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

• Thomas J Kipps, MD, PhD

  Director of the CLL Research Consortium and University of California San Diego

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 26, 2010
• First Posted: August 30, 2010
• Study Start: August 1, 2010
• Primary Completion: February 1, 2012
• Study Completion: August 1, 2012
• Last Updated: May 8, 2018
• Results First Posted: November 20, 2015

Record last verified: 2018-04

Locations

US (2)