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Ofatumumab and High-dose Methylprednisolone in Patients With Chronic Lymphocytic Leukemia (CLL) (CRC027)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01191190
First Posted: August 30, 2010
Last Update Posted: May 3, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Januario Castro, M.D., University of California, San Diego
  Purpose
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.

Condition Intervention Phase
CLL Drug: Ofatumumab/HDMP Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Ofatumumab in Combination With High-dose Methylprednisolone in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

Resource links provided by NLM:


Further study details as provided by Januario Castro, M.D., University of California, San Diego:

Primary Outcome Measures:
  • IwCLL-WG Defined Complete Response (CR) [ Time Frame: 2 months ]

    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


Secondary Outcome Measures:
  • IwCLL-WG Defined Overall Response Rate (ORR) [ Time Frame: 2 months ]
    Responses were assessed two months after completion of therapy. Overall Response Rate (ORR) = CR + PR

  • IwCLL-WG Defined Nodular Partial Response (PR) [ Time Frame: 2 months ]

    Responses were assessed two months after completion of therapy.

    Partial Response is defined as:

    • Greater than or equal to 50% decrease in blood absolute lymphocyte count from pre-treatment value; AND
    • Greater than or equal to 50% reduction in lymphadenopathy from pre-treatment value; AND
    • Greater than or equal to 50% reduction in splenomegaly/hepatomegaly from pre-treatment value.

    In addition, patients need to have at least ONE of the following:

    • Neutrophils ≥ 1,500/μl or ≥ 50% improvement from pre-treatment value; AND / OR
    • Platelets > 100,000/μl or 50% improvement from pre-treatment value; AND / OR
    • Hemoglobin > 11.0 gm/dl (non-transfused) or 50% improvement from pre-treatment value.

  • IwCLL-WG Defined Partial Response (PR) [ Time Frame: 2 months ]
    Responses were assessed two months after completion of therapy

  • IwCLL-WG Defined Stable Disease (SD) [ Time Frame: 2 months ]

    Responses were assessed two months after completion of therapy.

    Subjects who do not fulfill the criteria for complete or partial response as defined above but do not exhibit progressive disease will be considered as having stable disease.


  • IwCLL-WG Defined Progressive Disease (PD) [ Time Frame: 2 months ]

    Responses were assessed two months after completion of therapy

    Progressive Disease is defined as:

    • Greater than or equal to 50% increase in the products of at least two lymph nodes on two consecutive determinations two weeks apart (at least one lymph node must be ≥ 2 cm; or the appearance of a new palpable lymph node; OR
    • Greater than or equal to 50% increase in the size of the liver and/or spleen as determined by measurement below the respective costal margins; or appearance of palpable hepatomegaly or splenomegaly, which was not previously present; OR
    • Greater than or equal to 50% increase in the absolute number of circulating lymphocytes to at least 5,000μl; OR
    • Transformation to a more aggressive histology (i.e., Richter's syndrome or prolymphocytic leukemia with ≥ 56% prolymphocytes);

  • Progression-free Survival (PFS) [ Time Frame: 2 years ]
  • Treatment-Free Survival [ Time Frame: 2 years ]
  • Safety and Tolerability Measured Via Adverse Events [ Time Frame: 2 years ]
    Please see Adverse Event module for additional details.

  • Detectable Minimal Residual Disease (MRD) [ Time Frame: 2 years ]
    The patient who achieved a CR did not have detectable MRD in the bone marrow by four-color flow cytometry (<0.1% of cells).


Enrollment: 21
Study Start Date: August 2010
Study Completion Date: August 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ofatumumab/HDMP

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

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)

Other Names:
  • Arzerra
  • HuMax-CD20

Detailed Description:
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. Cycles 1-3 will be administered without scheduled interruption every 28 days for a total of 12 weeks of therapy. Patients will receive allopurinol for tumor-lysis prophylaxis and antimicrobial prophylaxis. Blood glucose levels will be monitored immediately after HDMP infusion by finger stick glucometry. Two months following completion of treatment a response assessment will occur per iwCLL guidelines. The treatment will be administered as outpatient, and each cycle will be four weeks in duration.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Previously treated patients with a diagnosis of CLL
  2. 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)
  3. 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
  4. Subjects must be 18 years of age or older, male or female.
  5. ECOG performance status of 0-2.
  6. Subjects must be able to give informed consent.
  7. 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.

Exclusion Criteria:

  1. Hepatitis BsAg positive, Hepatitis BcAb positive, and Hepatitis C positive patients.
  2. Known HIV positive patients.
  3. Diabetics.
  4. Patients with uncontrolled Autoimmune Hemolytic Anemia (AIHA) or autoimmune thrombocytopenia (ITP).
  5. 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)
  6. Inability to provide informed consent.
  7. Concurrent malignancy (excluding basal and squamous cell skin cancers).
  8. Active fungal, bacterial, and/or viral infection.
  9. History of peptic ulcer disease resulting in GI bleeding within the last 6 months.
  10. Untreated metabolic disorders such as hypothyroidism and Cushing's disease.
  11. History of steroid-induced psychosis.
  12. Estimated life expectancy of less than 3 months by the investigator's best clinical judgment.
  13. Serious medical condition that would render the subject medically unstable.
  14. Women who are pregnant or breast-feeding.
  15. History of Pancreatitis.
  16. History of Diverticulitis.
  17. Patients with known hypersensitivity to ofatumumab or known history of anaphylaxis to Rituximab or alemtuzumab.
  18. Concurrent use of other anti-cancer agents or treatments.
  19. Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01191190


Locations
United States, California
UC San Diego Moores Cancer Center
La Jolla, California, United States, 92093
University of California San Diego, Moores Cancer Center
La Jolla, California, United States, 92093
Sponsors and Collaborators
Januario Castro, M.D.
GlaxoSmithKline
Investigators
Principal Investigator: 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
  More Information

Additional Information:
Publications:
Responsible Party: Januario Castro, M.D., Principal Investigator, University of California, San Diego
ClinicalTrials.gov Identifier: NCT01191190     History of Changes
Other Study ID Numbers: 100429
First Submitted: August 26, 2010
First Posted: August 30, 2010
Results First Submitted: August 24, 2015
Results First Posted: November 20, 2015
Last Update Posted: May 3, 2017
Last Verified: March 2017

Keywords provided by Januario Castro, M.D., University of California, San Diego:
Leukemia
Chronic leukemia
Chronic Lymphocytic Leukemia
Relapsed
Refractory

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Prednisolone acetate
Methylprednisolone acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Ofatumumab
Antibodies, Monoclonal
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Protective Agents