A Phase II Study of Pomalidomide in Myelofibrosis With Myeloid Metaplasia

Browse trials for

• Primary Myelofibrosis 419
• Metaplasia 99

Keywords

• Celgene
• CC-4047
• Myelofibrosis
• myelofibrosis with myeloid metaplasia
• myeloid metaplasia
• JAK2
• CC-4047-MMM-001
• Prednisone
• Phase II
• pomalidomide
• bone marrow histology
• imids
• MMM
• Ashkenazi Jewish Population
• exposure to Thorotrast
• exposure to solvents (benzene and toluene)
• acute megakaryocytic leukemia
• history of polycythemia vera

Primary Myelofibrosis

419 studies on the registry are indexed under Primary Myelofibrosis; 117 are open to participants now.

This study's enrollment of 88 is above the median of 44 across 347 interventional studies indexed under Primary Myelofibrosis.

Lead sponsor

Celgene is the lead sponsor of 419 studies on the registry; 13 are open to participants now.

Of its 100 completed or terminated interventional studies of FDA-regulated products, 29 (29%) have results posted.

Study arms

• Experimental
  Prednisone

  Participants received oral prednisone from Day 1-28 of each 28-day cycle for up to 3 cycles (84 days), 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day, and pomalidomide placebo tablets on Days 1-28 for up to 12 cycles in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, participants were discontinued from the study.

  Drug: Prednisone · Drug: Placebo to pomalidomide

• Experimental
  Pomalidomide

  Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and prednisone placebo tablets on Days 1-28 for the first 3 cycles in the Double-Blind Treatment Phase. After the completion of Cycle 12 and upon unblinding, participants determined to have a complete remission (CR), partial remission (PR) or clinical improvement (CI) using the International Working Group (IWG) Response Criteria in the study protocol, were eligible to participate in the extension phase and continue to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle, until disease progression, unacceptable toxicity or voluntary withdrawal.

  Drug: Pomalidomide · Drug: Placebo to prednisone

• Experimental
  Pomalidomide 2 mg + Prednisone

  Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, participants determined to have a complete remission (CR), partial remission (PR) or clinical improvement (CI) using the International Working Group (IWG) Response Criteria in the study protocol, were eligible to participate in the extension phase and continue to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle, until disease progression, unacceptable toxicity or voluntary withdrawal.

  Drug: Pomalidomide · Drug: Prednisone

• Experimental
  Pomalidomide 0.5 mg + Prednisone

  Participants received 0.5 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase. After the completion of cycle 12 and upon unblinding, participants determined to have a complete remission (CR), partial remission (PR) or clinical improvement (CI) using the International Working Group (IWG) Response Criteria in the study protocol, were eligible to participate in the extension phase and continue to receive oral pomalidomide 0.5 mg daily, from Days 1-28 of each cycle, until disease progression, unacceptable toxicity or voluntary withdrawal.

  Drug: Pomalidomide · Drug: Prednisone

Interventions

• DrugPomalidomide

  Also known as: CC-4047, Pomalyst

• DrugPrednisone

  Participants will take oral prednisone in the evening for 3 cycles of 28 days each (up to 84 days). The dose will be as follows: 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day.

• DrugPlacebo to pomalidomide

  Matching pomalidomide placebo tablets

• DrugPlacebo to prednisone

  Matching prednisone placebo tablets

Primary outcomes

1. Percentage of Participants With a Clinical Response Within the First 6 Cycles of Treatment

   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 discontinued the study early without achieving clinical response were counted as non-responders.

   Time frame: Up to 168 days

Secondary outcomes

1. Percentage of Participants With a Clinical Response Within the First 12 Cycles of Treatment

   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 discontinued the study early without achieving clinical response were counted as non-responders.

   Time frame: Up to 336 days

2. Time to the First Clinical Response

   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 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.

   Time frame: Up to 168 days

3. Duration of First Clinical Response

   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 response was the earlier of the date of a hemoglobin increase of \< 2.0 g/dL and the date of a RBC transfusion at ≥ 56 days after the response started. For patients whose hemoglobin measurements were always ≥ 2.0 g/dL and never received a RBC transfusion after response started, the end date of the response was censored at the date of last hemoglobin measurement. Kaplan-Meier methodology was used.

   Time frame: Up to 40 months

4. Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores

   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-Being consists of 7 questions, the subscale score ranges from 0-28; * Anemia subscale consists of 20 questions, the subscale score ranges from 0-80; * Total FACT-An score ranges from 0-188.

   Time frame: Baseline and Cycle 6 (168 days).

5. Change From Baseline in Hemoglobin Concentration for Responders

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

   Time frame: Baseline, Cycle 6 (168 days)

6. Change From Baseline in Hemoglobin Concentration for Non-Responders

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

   Time frame: Baseline, Cycle 6 (168 days)

7. Change From Baseline in Likert Abdominal Pain Scale

   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.

   Time frame: Baseline and Cycle 6 (168 days)

8. Percentage of Participants With Clinical Response by Baseline JAK2 Assessment

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

   Time frame: Up to 336 days

9. Number of Participants With Adverse Events (AEs)

   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; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening; Grade 5 = Death. The Investigator determined the relationship between study drug and the occurrence of an AE as "Not Related" or "Related" (since the study was double-blinded, a patient receiving only prednisone could have an AE that was judged as related to pomalidomide, and vice-versa).

   Time frame: From date of the first dose of the study drug until discontinuation or the data cut-off date (up to approximately 45 months).

Baseline characteristics

1 further baseline measures are reported on the registry.

Publications

• Barosi G, et al. Decrease Of T Regulatory Cells In Patients With Myelofibrosis Receiving Ruxolitinib. Presented at American Society of Hematology 2013, December 7-10, 2013, New Orleans, LA. Abstract No. 4057. Blood, 2013;122(21)