Ofatumumab and High-dose Methylprednisolone in Patients W... | NCT01191190

NCT01191190

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
GlaxoSmithKline	INDUSTRY

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
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)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
IwCLL-WG Defined Overall Response Rate (ORR)	Responses were assessed two months after completion of therapy. Overall Response Rate (ORR) = CR + PR	2 months
IwCLL-WG Defined Nodular Partial Response (PR)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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.
History of Diverticulitis.
Patients with known hypersensitivity to ofatumumab or known history of anaphylaxis to Rituximab or alemtuzumab.
Concurrent use of other anti-cancer agents or treatments.
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).

Name	Affiliation	Role
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

Facility	Status	City	State	ZIP	Country	Contacts
UC San Diego Moores Cancer Center		La Jolla	California	92093	United States
University of California San Diego, Moores Cancer Center

PubMed Identifier	Type	Citation	Retractions
19693094	Background	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.
18754025	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.

Label	URL
Moore's UCSD Cancer Center	View source

Arm/Group Information

ID	Title	Description
FG000	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. 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)

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	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. 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)

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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

Posted

Number

participants

2 months

ID	Title	Description
OG000	Ofatumumab/HDMP

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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. 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)

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Infusion reaction	Immune system disorders		Systematic Assessment

Title	Organization	Phone	Extension	Email
Januario E Castro, MD	University of California, San Diego	(858) 822-6600		jecastro@ucsd.edu

ID	Term
D007938	Leukemia
D015451	Leukemia, Lymphocytic, Chronic, B-Cell
D012008	Recurrence

ID	Term
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases

ID	Term
C527517	ofatumumab

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.

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)