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

• Sponsor: Januario Castro, M.D. (Other)
• Overall Status: Completed
• CT.gov ID: NCT01191190
• Collaborator: GlaxoSmithKline (Industry)
• Enrollment: 21
• Locations: 2
• Arm: 1
• Duration (Months): 24
• Patients Per Site: 10.5
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
CLL	Drug: Ofatumumab/HDMP	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: N/A
• 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)
• Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: Feb 1, 2012
• Actual Study Completion Date: Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

1. IwCLL-WG Defined Complete Response (CR) [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

1. IwCLL-WG Defined Overall Response Rate (ORR) [2 months]

   Responses were assessed two months after completion of therapy. Overall Response Rate (ORR) = CR + PR

2. IwCLL-WG Defined Nodular Partial Response (PR) [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.

3. IwCLL-WG Defined Partial Response (PR) [2 months]

   Responses were assessed two months after completion of therapy

4. IwCLL-WG Defined Stable Disease (SD) [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.

5. IwCLL-WG Defined Progressive Disease (PD) [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);

6. Progression-free Survival (PFS) [2 years]

7. Treatment-Free Survival [2 years]

8. Safety and Tolerability Measured Via Adverse Events [2 years]

   Please see Adverse Event module for additional details.

9. Detectable Minimal Residual Disease (MRD) [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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

1. 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

2. Subjects must be 18 years of age or older, male or female.

3. ECOG performance status of 0-2.

4. Subjects must be able to give informed consent.

5. 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

Locations

	Site	City	State	Country	Postal Code
1	UC San Diego Moores Cancer Center	La Jolla	California	United States	92093
2	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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

• 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. Erratum in: Leukemia. 2009 Dec;23(12):2326.
• 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.

• Responsible Party: Januario Castro, M.D., Principal Investigator, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT01191190
• Other Study ID Numbers: 100429
• First Posted: Aug 30, 2010
• Last Update Posted: May 8, 2018
• Last Verified: Apr 1, 2018

• Keywords provided by Januario Castro, M.D., Principal Investigator, 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; Ofatumumab

Study Results

Participant Flow

Arm/Group Title	Ofatumumab/HDMP
Arm/Group Description	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)
Period Title: Overall Study
STARTED	21
COMPLETED	20
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Ofatumumab/HDMP
Arm/Group Description	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)
Overall Participants	21
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	11 52.4%
>=65 years	10 47.6%
Sex: Female, Male (Count of Participants)
Female	3 14.3%
Male	18 85.7%
Region of Enrollment (Count of Participants)
United States	21 100%

Outcome Measures

1. Primary Outcome

Title	IwCLL-WG Defined Complete Response (CR)
Description	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
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ofatumumab/HDMP
Arm/Group Description	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)
Measure Participants	21
Number [participants]	1 4.8%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ofatumumab/HDMP
Arm/Group Description	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)
Measure Participants	21
Number [participants]	17 81%

3. Secondary Outcome

Title	IwCLL-WG Defined Nodular Partial Response (PR)
Description	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.
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ofatumumab/HDMP
Arm/Group Description	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)
Measure Participants	21
Number [participants]	2 9.5%

4. Secondary Outcome

Title	IwCLL-WG Defined Partial Response (PR)
Description	Responses were assessed two months after completion of therapy
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ofatumumab/HDMP
Arm/Group Description	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)
Measure Participants	21
Number [participants]	14 66.7%

5. Secondary Outcome

Title	IwCLL-WG Defined Stable Disease (SD)
Description	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.
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ofatumumab/HDMP
Arm/Group Description	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)
Measure Participants	21
Number [participants]	3 14.3%

6. Secondary Outcome

Title	IwCLL-WG Defined Progressive Disease (PD)
Description	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);
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ofatumumab/HDMP
Arm/Group Description	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)
Measure Participants	21
Number [participants]	1 4.8%

7. Secondary Outcome

Title	Progression-free Survival (PFS)
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ofatumumab/HDMP
Arm/Group Description	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)
Measure Participants	21
Median (Full Range) [months]	9.9

8. Secondary Outcome

Title	Treatment-Free Survival
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ofatumumab/HDMP
Arm/Group Description	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)
Measure Participants	21
Median (Full Range) [months]	12.1

9. Secondary Outcome

Title	Safety and Tolerability Measured Via Adverse Events
Description	Please see Adverse Event module for additional details.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Total number of participants who had at least 1 adverse event

Arm/Group Title	Ofatumumab/HDMP
Arm/Group Description	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)
Measure Participants	21
Number [participants]	21 100%

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ofatumumab/HDMP
Arm/Group Description	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)
Measure Participants	1
Number [participants]	0 0%

Adverse Events

Arm/Group Title	Ofatumumab/HDMP
Arm/Group Description	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)
All Cause Mortality
	Ofatumumab/HDMP
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ofatumumab/HDMP
	Affected / at Risk (%)	# Events
Total	0/21 (0%)
Other (Not Including Serious) Adverse Events
	Ofatumumab/HDMP
	Affected / at Risk (%)	# Events
Total	21/21 (100%)
Blood and lymphatic system disorders
Anemia (CTCAE)	18/21 (85.7%)
Thrombocytopenia (CTCAE)	15/21 (71.4%)
Neutropenia (CTCAE)	10/21 (47.6%)
Leukocytopenia, not captured by neutropenia	2/21 (9.5%)
Bleeding (superficial)	2/21 (9.5%)
Gastrointestinal disorders
Elevated ALT	7/21 (33.3%)
Dyspepsia	7/21 (33.3%)
Elevated AST	6/21 (28.6%)
Nausea	4/21 (19%)
Anorexia	3/21 (14.3%)
Diarrhea	3/21 (14.3%)
Abdominal Distension	2/21 (9.5%)
Constipation	2/21 (9.5%)
Anorexia	2/21 (9.5%)
Hyperbilirubinemia	1/21 (4.8%)
General disorders
Cough	9/21 (42.9%)
Edema	7/21 (33.3%)
Dizziness	5/21 (23.8%)
Hypotension	4/21 (19%)
Tachycardia	4/21 (19%)
Dyspnea	4/21 (19%)
Palpitations	3/21 (14.3%)
Arrythmia	2/21 (9.5%)
Non-ST elevation Myocardial Infarction	1/21 (4.8%)
Hyperglycemia	18/21 (85.7%)
Fatigue	13/21 (61.9%)
Hypocalcemia	7/21 (33.3%)
metabolic other Elevated LDH-	7/21 (33.3%)
Hypokalemia	5/21 (23.8%)
Diaphoresis	4/21 (19%)
Night Sweats	4/21 (19%)
Weight Gain	4/21 (19%)
Hypokalemia	3/21 (14.3%)
Weakness	3/21 (14.3%)
Fever	3/21 (14.3%)
Hypernatremia	3/21 (14.3%)
Hyperuricemia	3/21 (14.3%)
Weight Loss	3/21 (14.3%)
Rigors/ chills	2/21 (9.5%)
Hyperkalemia	1/21 (4.8%)
Insomnia	15/21 (71.4%)
Anxiety	7/21 (33.3%)
Paraethesias	5/21 (23.8%)
Headache	4/21 (19%)
Tremor	3/21 (14.3%)
Visual change	2/21 (9.5%)
Neuropathy	2/21 (9.5%)
Agitation	2/21 (9.5%)
Pharyngolaryngeal pain/itching	4/21 (19%)
Rhinnorhea	4/21 (19%)
Allergic rhinitis	3/21 (14.3%)
Dysguesia	3/21 (14.3%)
Weak Voice	2/21 (9.5%)
Dysphagia	1/21 (4.8%)
Oral ulcers	1/21 (4.8%)
Abdominal Pain	5/21 (23.8%)
Myalgia	2/21 (9.5%)
Lower Back Pain	2/21 (9.5%)
Immune system disorders
Infusion reaction	11/21 (52.4%)
Flushing	5/21 (23.8%)
Allergic Reaction	1/21 (4.8%)
Infections and infestations
Upper Respiratory Infection	8/21 (38.1%)
Pneumonia	1/21 (4.8%)
Sinusitis	1/21 (4.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-melanoma skin cancer	1/21 (4.8%)
Renal and urinary disorders
Creatinine elevation	8/21 (38.1%)
Kidney stones	2/21 (9.5%)
Urinary frequency	1/21 (4.8%)
Penile blister	1/21 (4.8%)
Skin and subcutaneous tissue disorders
Rash	16/21 (76.2%)
Pruritis	11/21 (52.4%)
Actinic Keratosis	1/21 (4.8%)
Atypical Squamous Proliferation, Folliculitis	1/21 (4.8%)
Lichenoid Dermatitis	1/21 (4.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.