Trial Outcomes & Findings for Ofatumumab and High-dose Methylprednisolone in Patients With Chronic Lymphocytic Leukemia (CLL) (NCT NCT01191190)
NCT ID: NCT01191190
Last Updated: 2018-05-08
Results Overview
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
COMPLETED
PHASE2
21 participants
2 months
2018-05-08
Participant Flow
Participant milestones
| Measure |
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)
|
|---|---|
|
Overall Study
STARTED
|
21
|
|
Overall Study
COMPLETED
|
20
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
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)
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
Ofatumumab and High-dose Methylprednisolone in Patients With Chronic Lymphocytic Leukemia (CLL)
Baseline characteristics by cohort
| Measure |
Ofatumumab/HDMP
n=21 Participants
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)
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
11 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
10 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
21 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 2 monthsResponses 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
Outcome measures
| Measure |
Ofatumumab/HDMP
n=21 Participants
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)
|
|---|---|
|
IwCLL-WG Defined Complete Response (CR)
|
1 participants
|
SECONDARY outcome
Timeframe: 2 monthsResponses were assessed two months after completion of therapy. Overall Response Rate (ORR) = CR + PR
Outcome measures
| Measure |
Ofatumumab/HDMP
n=21 Participants
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)
|
|---|---|
|
IwCLL-WG Defined Overall Response Rate (ORR)
|
17 participants
|
SECONDARY outcome
Timeframe: 2 monthsResponses 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.
Outcome measures
| Measure |
Ofatumumab/HDMP
n=21 Participants
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)
|
|---|---|
|
IwCLL-WG Defined Nodular Partial Response (PR)
|
2 participants
|
SECONDARY outcome
Timeframe: 2 monthsResponses were assessed two months after completion of therapy
Outcome measures
| Measure |
Ofatumumab/HDMP
n=21 Participants
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)
|
|---|---|
|
IwCLL-WG Defined Partial Response (PR)
|
14 participants
|
SECONDARY outcome
Timeframe: 2 monthsResponses 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.
Outcome measures
| Measure |
Ofatumumab/HDMP
n=21 Participants
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)
|
|---|---|
|
IwCLL-WG Defined Stable Disease (SD)
|
3 participants
|
SECONDARY outcome
Timeframe: 2 monthsResponses 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);
Outcome measures
| Measure |
Ofatumumab/HDMP
n=21 Participants
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)
|
|---|---|
|
IwCLL-WG Defined Progressive Disease (PD)
|
1 participants
|
SECONDARY outcome
Timeframe: 2 yearsOutcome measures
| Measure |
Ofatumumab/HDMP
n=21 Participants
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)
|
|---|---|
|
Progression-free Survival (PFS)
|
9.9 months
Interval 2.0 to 34.0
|
SECONDARY outcome
Timeframe: 2 yearsOutcome measures
| Measure |
Ofatumumab/HDMP
n=21 Participants
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)
|
|---|---|
|
Treatment-Free Survival
|
12.1 months
Interval 2.0 to 36.0
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: Total number of participants who had at least 1 adverse event
Please see Adverse Event module for additional details.
Outcome measures
| Measure |
Ofatumumab/HDMP
n=21 Participants
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)
|
|---|---|
|
Safety and Tolerability Measured Via Adverse Events
|
21 participants
|
SECONDARY outcome
Timeframe: 2 yearsThe patient who achieved a CR did not have detectable MRD in the bone marrow by four-color flow cytometry (\<0.1% of cells).
Outcome measures
| Measure |
Ofatumumab/HDMP
n=1 Participants
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)
|
|---|---|
|
Detectable Minimal Residual Disease (MRD)
|
0 participants
|
Adverse Events
Ofatumumab/HDMP
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Ofatumumab/HDMP
n=21 participants at risk
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)
|
|---|---|
|
Immune system disorders
Infusion reaction
|
52.4%
11/21
|
|
Immune system disorders
Flushing
|
23.8%
5/21
|
|
Immune system disorders
Allergic Reaction
|
4.8%
1/21
|
|
General disorders
Cough
|
42.9%
9/21
|
|
General disorders
Edema
|
33.3%
7/21
|
|
General disorders
Dizziness
|
23.8%
5/21
|
|
General disorders
Hypotension
|
19.0%
4/21
|
|
General disorders
Tachycardia
|
19.0%
4/21
|
|
General disorders
Dyspnea
|
19.0%
4/21
|
|
General disorders
Palpitations
|
14.3%
3/21
|
|
General disorders
Arrythmia
|
9.5%
2/21
|
|
General disorders
Non-ST elevation Myocardial Infarction
|
4.8%
1/21
|
|
Skin and subcutaneous tissue disorders
Rash
|
76.2%
16/21
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
52.4%
11/21
|
|
Skin and subcutaneous tissue disorders
Actinic Keratosis
|
4.8%
1/21
|
|
Skin and subcutaneous tissue disorders
Atypical Squamous Proliferation, Folliculitis
|
4.8%
1/21
|
|
Skin and subcutaneous tissue disorders
Lichenoid Dermatitis
|
4.8%
1/21
|
|
Gastrointestinal disorders
Elevated ALT
|
33.3%
7/21
|
|
Gastrointestinal disorders
Dyspepsia
|
33.3%
7/21
|
|
Gastrointestinal disorders
Elevated AST
|
28.6%
6/21
|
|
Gastrointestinal disorders
Nausea
|
19.0%
4/21
|
|
Gastrointestinal disorders
Anorexia
|
9.5%
2/21
|
|
Gastrointestinal disorders
Diarrhea
|
14.3%
3/21
|
|
Gastrointestinal disorders
Abdominal Distension
|
9.5%
2/21
|
|
Gastrointestinal disorders
Constipation
|
9.5%
2/21
|
|
Gastrointestinal disorders
Hyperbilirubinemia
|
4.8%
1/21
|
|
Blood and lymphatic system disorders
Anemia (CTCAE)
|
85.7%
18/21
|
|
Blood and lymphatic system disorders
Thrombocytopenia (CTCAE)
|
71.4%
15/21
|
|
Blood and lymphatic system disorders
Neutropenia (CTCAE)
|
47.6%
10/21
|
|
Blood and lymphatic system disorders
Leukocytopenia, not captured by neutropenia
|
9.5%
2/21
|
|
Blood and lymphatic system disorders
Bleeding (superficial)
|
9.5%
2/21
|
|
Infections and infestations
Upper Respiratory Infection
|
38.1%
8/21
|
|
Infections and infestations
Pneumonia
|
4.8%
1/21
|
|
Infections and infestations
Sinusitis
|
4.8%
1/21
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-melanoma skin cancer
|
4.8%
1/21
|
|
General disorders
Hyperglycemia
|
85.7%
18/21
|
|
General disorders
Fatigue
|
61.9%
13/21
|
|
General disorders
Hypocalcemia
|
33.3%
7/21
|
|
General disorders
metabolic other Elevated LDH-
|
33.3%
7/21
|
|
General disorders
Hypokalemia
|
14.3%
3/21
|
|
General disorders
Diaphoresis
|
19.0%
4/21
|
|
General disorders
Night Sweats
|
19.0%
4/21
|
|
General disorders
Weight Gain
|
19.0%
4/21
|
|
General disorders
Weakness
|
14.3%
3/21
|
|
General disorders
Fever
|
14.3%
3/21
|
|
General disorders
Hypernatremia
|
14.3%
3/21
|
|
General disorders
Hyperuricemia
|
14.3%
3/21
|
|
General disorders
Weight Loss
|
14.3%
3/21
|
|
General disorders
Rigors/ chills
|
9.5%
2/21
|
|
General disorders
Hyperkalemia
|
4.8%
1/21
|
|
General disorders
Insomnia
|
71.4%
15/21
|
|
General disorders
Anxiety
|
33.3%
7/21
|
|
General disorders
Paraethesias
|
23.8%
5/21
|
|
General disorders
Headache
|
19.0%
4/21
|
|
General disorders
Tremor
|
14.3%
3/21
|
|
General disorders
Visual change
|
9.5%
2/21
|
|
General disorders
Neuropathy
|
9.5%
2/21
|
|
General disorders
Agitation
|
9.5%
2/21
|
|
General disorders
Pharyngolaryngeal pain/itching
|
19.0%
4/21
|
|
General disorders
Rhinnorhea
|
19.0%
4/21
|
|
General disorders
Allergic rhinitis
|
14.3%
3/21
|
|
General disorders
Dysguesia
|
14.3%
3/21
|
|
General disorders
Weak Voice
|
9.5%
2/21
|
|
General disorders
Dysphagia
|
4.8%
1/21
|
|
General disorders
Oral ulcers
|
4.8%
1/21
|
|
General disorders
Abdominal Pain
|
23.8%
5/21
|
|
General disorders
Myalgia
|
9.5%
2/21
|
|
General disorders
Lower Back Pain
|
9.5%
2/21
|
|
Renal and urinary disorders
Creatinine elevation
|
38.1%
8/21
|
|
Renal and urinary disorders
Kidney stones
|
9.5%
2/21
|
|
Renal and urinary disorders
Urinary frequency
|
4.8%
1/21
|
|
Renal and urinary disorders
Penile blister
|
4.8%
1/21
|
Additional Information
Januario E Castro, MD
University of California, San Diego
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place