NCT00463385

A Phase II Study of Pomalidomide in Myelofibrosis With Myeloid Metaplasia

Completed Phase 2 Results posted Last updated 20 November 2019

What this trial tests

Phase 2 trial testing Pomalidomide in Myelofibrosis With Myeloid Metaplasia in 88 participants. Completed in 31 December 2013.

Timeline

1 April 2007

Primary endpoint
1 May 2009

31 December 2013

Quick facts

Lead sponsor	Celgene
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	88
Start date	1 April 2007
Primary completion	1 May 2009
Estimated completion	31 December 2013
Sites	11 locations across Italy, Austria, United Kingdom, United States, Spain

Drugs / interventions tested

• Pomalidomide — full drug profile →
• Prednisone (prednisone) — full drug profile →
• Placebo to pomalidomide — full drug profile →
• Placebo to prednisone

Conditions studied

• Myelofibrosis With Myeloid Metaplasia — all drugs for Myelofibrosis With Myeloid Metaplasia →
• Myeloid Metaplasia — all drugs for Myeloid Metaplasia →
• Myelofibrosis — all drugs for Myelofibrosis →

Sponsor

Celgene — full company profile →

Who can join

18 and older, any sex, with Myelofibrosis With Myeloid Metaplasia or Myeloid Metaplasia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With a Clinical Response Within the First 6 Cycles of Treatment Primary · Up to 168 days

A clinical responder was defined as either: 1. A baseline red blood cell (RBC)-transfusion-dependent participant with a ≥ 56 consecutive day RBC transfusion-free period after the first dose of study drug, or 2. A baseline RBC-transfusion-independent participant with an increase in hemoglobin of 2.0 g/dL or more from baseline for ≥ 56 consecutive days in the absence of RBC transfusions, or 3. A participant with either a ≥ 50% reduction in palpable splenomegaly of a spleen that was ≥ 10 cm at baseline or a spleen that was palpable at \> 5 cm and became not palpable. Participants who discontinu

Group	Value	95% CI
Prednisone	55.0	31.53 – 76.94
Pomalidomide 2 mg	23.5	6.81 – 49.90
Pomalidomide 2 mg + Prednisone	21.1	6.05 – 45.57
Pomalidomide 0.5 mg + Prednisone	47.6	25.71 – 70.22

Percentage of Participants With a Clinical Response Within the First 12 Cycles of Treatment Secondary · Up to 336 days

A clinical responder was defined as either: 1. A baseline red blood cell (RBC)-transfusion-dependent participant with a ≥ 56 consecutive day RBC transfusion-free period after the first dose of study drug, or 2. A baseline RBC-transfusion-independent participant with an increase in hemoglobin of 2.0 g/dL or more from baseline for ≥ 56 consecutive days in the absence of RBC transfusions, or 3. A participant with either a ≥ 50% reduction in palpable splenomegaly of a spleen that was ≥ 10 cm at baseline or a spleen that was palpable at \> 5 cm and became not palpable. Participants who discontinu

Group	Value	95% CI
Prednisone	50.0	28.22 – 71.78
Pomalidomide 2 mg	18.2	5.19 – 40.28
Pomalidomide 2 mg + Prednisone	18.2	5.19 – 40.28
Pomalidomide 0.5 mg + Prednisone	45.5	24.39 – 67.79

Time to the First Clinical Response Secondary · Up to 168 days

The time to the first clinical response achieved within 168 days after the first study drug dosing date was calculated for participants who achieved a clinical response as: Start date of the first clinical response - the first study drug date +1. A clinical responder was defined as either: 1. A baseline red blood cell (RBC)-transfusion-dependent participant with a ≥ 56 consecutive day RBC transfusion-free period after the first dose of study drug, or 2. A baseline RBC-transfusion-independent participant with an increase in hemoglobin of 2.0 g/dL or more from baseline for ≥ 56 consecutive da

Group	Value	95% CI
Prednisone	0.3	0.1 – 15.6
Pomalidomide 2 mg	8.0	2.6 – 17.3
Pomalidomide 2 mg + Prednisone	10.1	0.1 – 20.0
Pomalidomide 0.5 mg + Prednisone	1.2	0.1 – 16.6

Duration of First Clinical Response Secondary · Up to 40 months

For RBC-transfusion-dependent patients, duration of response was calculated as the last day of response - first day of response +1, where the last day of response was the date of the first RBC-transfusion administrated at or more than 56 days after the response started. For patients who did not receive a subsequent transfusion after the response started, the end date of response was censored at the day of last hemoglobin assessment. For RBC-transfusion-independent patients, the duration of response was calculated as the last day of response - first day of response +1, where the last day of re

Group	Value	95% CI
Prednisone	3.7	3.0 – 6.6
Pomalidomide 2 mg	NA	4.7 – NA
Pomalidomide 2 mg + Prednisone	6.0	2.3 – 9.8
Pomalidomide 0.5 mg + Prednisone	10.6	2.8 – 16.1

Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores Secondary · Baseline and Cycle 6 (168 days).

The FACT-An comprises the four subscales of the 27-item FACT-General Scale (FACT-G), Physical Well-being, Social/Family Well-being, Emotion Well-being, Functional Well-Being, and the Additional Concerns Anemia subscale. Questions are rated on a scale from 0 to 4, where higher scores indicate more impact on quality of life. * Physical Well-being consists of 7 questions, the subscale score ranges from 0-28; * Social/Family Well-being consists of 7 questions, the subscale score ranges from 0-28; * Emotion Well-being consists of 6 questions, the subscale score ranges from 0-24; * Functional Well-

Physical Well-Being subscale

Group	Value	95% CI
Prednisone	0.6	± 1.50
Pomalidomide 2 mg	0.4	± 6.42
Pomalidomide 2 mg + Prednisone	5.3	± 4.04
Pomalidomide 0.5 mg + Prednisone	2.3	± 2.26

Social/Family Well-Being subscale

Group	Value	95% CI
Prednisone	1.9	± 3.08
Pomalidomide 2 mg	-1.9	± 2.59
Pomalidomide 2 mg + Prednisone	1.7	± 3.79
Pomalidomide 0.5 mg + Prednisone	0.9	± 6.84

Emotional Well-Being subscale

Group	Value	95% CI
Prednisone	1.3	± 3.32
Pomalidomide 2 mg	0.0	± 4.76
Pomalidomide 2 mg + Prednisone	-0.3	± 0.58
Pomalidomide 0.5 mg + Prednisone	1.7	± 3.47

Functional Well-Being subscale

Group	Value	95% CI
Prednisone	0.9	± 4.14
Pomalidomide 2 mg	-2.1	± 8.99
Pomalidomide 2 mg + Prednisone	2.7	± 3.06
Pomalidomide 0.5 mg + Prednisone	2.5	± 6.50

Anemia subscale

Group	Value	95% CI
Prednisone	1.2	± 9.47
Pomalidomide 2 mg	2.3	± 21.34
Pomalidomide 2 mg + Prednisone	19.3	± 18.93
Pomalidomide 0.5 mg + Prednisone	5.8	± 8.85

Total FACT-An score

Group	Value	95% CI
Prednisone	2.3	± 12.42
Pomalidomide 2 mg	1.6	± 36.51
Pomalidomide 2 mg + Prednisone	27.3	± 25.74
Pomalidomide 0.5 mg + Prednisone	11.4	± 13.51

Change From Baseline in Hemoglobin Concentration for Responders Secondary · Baseline, Cycle 6 (168 days)

Change from Baseline in hemoglobin for participants with a clinical response within the first 6 cycles of treatment.

Group	Value	95% CI
Prednisone	1.4	-0.5 – 4.1
Pomalidomide 2 mg	2.0	0.7 – 3.2
Pomalidomide 0.5 mg + Prednisone	-0.1	-1.9 – 3.9

Change From Baseline in Hemoglobin Concentration for Non-Responders Secondary · Baseline, Cycle 6 (168 days)

Change from Baseline in hemoglobin for participants without a clinical response within the first 6 cycles of treatment.

Group	Value	95% CI
Prednisone	1.2	-0.2 – 2.7
Pomalidomide 2 mg	0.1	-0.8 – 1.3
Pomalidomide 2 mg + Prednisone	-0.8	-2.0 – 1.9
Pomalidomide 0.5 mg + Prednisone	0.5	-0.3 – 1.0

Change From Baseline in Likert Abdominal Pain Scale Secondary · Baseline and Cycle 6 (168 days)

Participants rated abdominal discomfort or pain over the previous week on a scale from zero to ten, where zero is no discomfort or pain and ten is the worst pain imaginable.

Group	Value	95% CI
Prednisone	0.3	± 1.83
Pomalidomide 2 mg	-1.0	± 3.11
Pomalidomide 2 mg + Prednisone	0.3	± 1.15
Pomalidomide 0.5 mg + Prednisone	-0.1	± 1.68

Percentage of Participants With Clinical Response by Baseline JAK2 Assessment Secondary · Up to 336 days

Percentage of participants who achieved a clinical response, presented by participants with positive and negative janus kinase 2 (JAK2) V617F mutation results at Baseline.

Group	Value	95% CI
Prednisone, Positive JAK2	46.2
Pomalidomide 2 mg, PositiveJAK2	27.3
Pomalidomide 2 mg + Prednisone, Positive JAK2	30.0
Pomalidomide 0.5 mg + Prednisone, Positive JAK2	66.7
Prednisone, Negative JAK2	50.0
Pomalidomide 2 mg, Negative JAK2	28.6
Pomalidomide 2 mg + Prednisone, Negative JAK2	12.5
Pomalidomide 0.5 mg + Prednisone, Negative JAK2	25.0

Number of Participants With Adverse Events (AEs) Secondary · From date of the first dose of the study drug until discontinuation or the data cut-off date (up to approximately 45 months).

A serious AE (SAE) was defined as any AE which resulted in death or was life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or constituted an important medical event (events that may have jeopardized the patient or required intervention to prevent one of the outcomes listed above). The severity of AEs were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 3.0) or according to the following scale: Grade 1 = Mild; Gr

At least one AE

Group	Value	95% CI
Prednisone	20
Pomalidomide 2 mg	21
Pomalidomide 2 mg + Prednisone	18
Pomalidomide 0.5 mg + Prednisone	21

At least one AE related to pomalidomide

Group	Value	95% CI
Prednisone	15
Pomalidomide 2 mg	17
Pomalidomide 2 mg + Prednisone	16
Pomalidomide 0.5 mg + Prednisone	15

At least one AE related to prednisone

Group	Value	95% CI
Prednisone	10
Pomalidomide 2 mg	10
Pomalidomide 2 mg + Prednisone	11
Pomalidomide 0.5 mg + Prednisone	5

At least one Grade 3-4 AE

Group	Value	95% CI
Prednisone	10
Pomalidomide 2 mg	14
Pomalidomide 2 mg + Prednisone	13
Pomalidomide 0.5 mg + Prednisone	15

At least one Grade 3-4 AE related to pomalidomide

Group	Value	95% CI
Prednisone	6
Pomalidomide 2 mg	7
Pomalidomide 2 mg + Prednisone	11
Pomalidomide 0.5 mg + Prednisone	6

At least one Grade 3-4 AE related to prednisone

Group	Value	95% CI
Prednisone	5
Pomalidomide 2 mg	2
Pomalidomide 2 mg + Prednisone	6
Pomalidomide 0.5 mg + Prednisone	3

At least one SAE

Group	Value	95% CI
Prednisone	6
Pomalidomide 2 mg	10
Pomalidomide 2 mg + Prednisone	11
Pomalidomide 0.5 mg + Prednisone	8

At least one SAE related to pomalidomide

Group	Value	95% CI
Prednisone	4
Pomalidomide 2 mg	6
Pomalidomide 2 mg + Prednisone	8
Pomalidomide 0.5 mg + Prednisone	3

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first dose of the study drug through to 30 days after the last dose; up to the data cut-off date of 18 December 2013; up to 81 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Prednisone

Serious: 6/22 (27%)

Deaths: —

Pomalidomide 2 mg

Serious: 10/22 (45%)

Deaths: —

Pomalidomide 2 mg + Prednisone

Serious: 11/19 (58%)

Deaths: —

Pomalidomide 0.5 mg + Prednisone

Serious: 9/22 (41%)

Deaths: —

Serious adverse events (66 terms)

Reaction	System	Prednisone	Pomalidomide 2 mg	Pomalidomide 2 mg + Predni…	Pomalidomide 0.5 mg + Pred…
Pneumonia	Infections and infestations	—	—	—	—
Gastrointestinal Haemorrhage	Gastrointestinal disorders	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—
Pyrexia	General disorders	—	—	—	—
Renal Failure Acute	Renal and urinary disorders	—	—	—	—
Atrial Flutter	Cardiac disorders	—	—	—	—
Cardiac Failure	Cardiac disorders	—	—	—	—
Myocardial Infarction	Cardiac disorders	—	—	—	—
Atrial Fibrillation	Cardiac disorders	—	—	—	—
Bradycardia	Cardiac disorders	—	—	—	—
Cardiac Failure Acute	Cardiac disorders	—	—	—	—
Cardiac Failure Congestive	Cardiac disorders	—	—	—	—
Left Ventricular Dysfunction	Cardiac disorders	—	—	—	—
Right Ventricular Failure	Cardiac disorders	—	—	—	—
Septic Shock	Infections and infestations	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—
Cellulitis	Infections and infestations	—	—	—	—
Diverticulitis	Infections and infestations	—	—	—	—
Lobar Pneumonia	Infections and infestations	—	—	—	—
Lung Infection Pseudomonal	Infections and infestations	—	—	—	—
Perirectal Abscess	Infections and infestations	—	—	—	—
Respiratory Tract Infection	Infections and infestations	—	—	—	—
Urinary Tract Infection Enterococcal	Infections and infestations	—	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—	—	—

Other adverse events (114 terms — click to expand)

Reaction	System	Prednisone	Pomalidomide 2 mg	Pomalidomide 2 mg + Predni…	Pomalidomide 0.5 mg + Pred…
Oedema Peripheral	General disorders	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—
Fatigue	General disorders	—	—	—	—
Pyrexia	General disorders	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—
Muscle Spasms	Musculoskeletal and connective tissue disorders	—	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Abdominal Pain	Gastrointestinal disorders	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—	—
Night Sweats	Skin and subcutaneous tissue disorders	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—	—
Chills	General disorders	—	—	—	—
Asthenia	General disorders	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—
Paraesthesia	Nervous system disorders	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
Pain In Extremity	Musculoskeletal and connective tissue disorders	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—
Erythema	Skin and subcutaneous tissue disorders	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—
Vision Blurred	Eye disorders	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—
Nasal Congestion	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Oropharyngeal Pain	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Abdominal Pain Upper	Gastrointestinal disorders	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—
Abdominal Distension	Gastrointestinal disorders	—	—	—	—
Burning Sensation	Nervous system disorders	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—
Bone Pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Muscular Weakness	Musculoskeletal and connective tissue disorders	—	—	—	—
Upper Respiratory Tract Infection	Infections and infestations	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—
Ecchymosis	Skin and subcutaneous tissue disorders	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—

Most-reported serious reactions: Pneumonia, Gastrointestinal Haemorrhage, Anaemia, Pyrexia, Renal Failure Acute, Atrial Flutter, Cardiac Failure, Myocardial Infarction.

Data from ClinicalTrials.gov NCT00463385 adverse events section.

Sponsor's own description

The purpose of this study is to determine the safety of and to select a treatment regimen of pomalidomide (CC-4047) either as single-agent or in combination with prednisone to study further in patients with myelofibrosis with myeloid metaplasia (MMM).

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Pomalidomide is active in the treatment of anemia associated with myelofibrosis.
   Tefferi A, Verstovsek S, Barosi G, Passamonti F, et al · · 2009 · cited 136× · PMID 19652059 · DOI 10.1200/jco.2008.21.7356