Cancer, Chemotherapy-Induced Thrombocytopenia, Hodgkin's Lymphoma, Non-Hodgkin's Lymphoma, Oncology, Thrombocytopenia
Conditions
Keywords
NHL, chemotherapy induced thrombocytopenia, CIT, ICE, RICE, Hodgkin's Lymphoma, Non-Hodgkin's Lymphoma, CHOP, ESHAP, DHAP, R-CHOP, R-ESHAP, R-DHAP
Brief summary
The purpose of this study is to identify a well-tolerated, effective dose and schedule of AMG 531 for the treatment of Chemotherapy Induced Thrombocytopenia (CIT) in subjects with lymphoma receiving multi-cycle chemotherapy.
Interventions
BIOLOGICALAMG 531
Planned Cohorts: 1. 100 mcg, 2. 300 mcg, 3. 700 mcg, 4. 1000 mcg; Optional Cohorts: 5. cohort expansion, 6. schedule change, 7. new dose
Sponsors
Amgen
Study design
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed Hodgkin's lymphoma or Non-Hodgkin's lymphoma receiving Q14, Q21, or Q28 day CHOP, ICE, ESHAP, or DHAP chemotherapy; with or without Rituximab * Has adequate bone marrow function; platelet count \> 100 x 10\^9/L on the day of initiation of the on study chemotherapy of the next treatment cycle and absolute neutrophil count, ANC \> or = 1 x 10\^9/L, and hemoglobin \> or = 9.5 g/dL * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Has adequate liver function * must be able to receive the same chemotherapy regimen during the first treatment cycle as was received during the prior qualifying cycle * must experience Common Terminology Criteria (CTC) grade 3 or 4 thrombocytopenia (platelet count \< 50 x 10\^9/L) as a result of the chemotherapy administered in the cycle immediately preceding study entry * has serum creatinine concentration \< or = 2 mg/dl
Exclusion criteria
* More that 1 prior relapse chemotherapy regimen * Sepsis, disseminated coagulation or any other condition that may exacerbate thrombocytopenia * Significant bleeding (CTC grade 3 or 4) * History of thromboembolic disease * Subjects who are identified by clinical history and/or serological testing to have either acute or chronic hepatitis B or C infection or to be HIV positive * Use of any nitrosourea or mitomycin-C * Has received any thrombocytopenic growth factor * Has received a marrow or peripheral blood stem cell infusion * Known hypersensitivity to any recombinant E. coli-derived product
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Platelet Nadir | 32 weeks | Change in platelet nadir from the previous qualifying cycle to the first treatment cycle. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Experiencing Grade 3 or 4 Thrombocytopenia | 32 weeks | Percentage of subjects experiencing grade 3 and/or 4 thrombocytopenia (\<50 x 10\^9/L, and \<25 x 10\^9/L) |
| Duration of Grade 3 or 4 Thrombocytopenia | 32 weeks | Duration of grade 3 and/or 4 thrombocytopenia (\<50 x 10\^9/L and \<25 x 10\^9/L, respectively) |
| Percentage of Subjects That Received Platelet Transfusions | 32 weeks | Percentage of subjects that received platelet transfusions during the first romiplostim treatment cycle |
Participant flow
Recruitment details
Participants were enrolled from 15 March 2006 through 28 April 2008
Participants by arm
| Arm | Count |
|---|---|
| Romiplostim 100 µg Romiplostim 100 µg administered by subcutaneous injection on the first day after chemotherapy | 8 |
| Romiplostim 300 µg Romiplostim 300 µg administered by subcutaneous injection on the first day after chemotherapy | 11 |
| Romiplostim 700 µg Romiplostim 700 µg administered by subcutaneous injection on the first day after chemotherapy | 11 |
| Romiplostim 1000 µg Romiplostim 1000 µg administered by subcutaneous injection on the first day after chemotherapy | 9 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 |
| Overall Study | Death | 0 | 0 | 1 | 0 |
| Overall Study | Disease progression | 0 | 1 | 0 | 0 |
| Overall Study | Other | 1 | 0 | 0 | 0 |
| Overall Study | Requirement for alternative therapy | 1 | 2 | 5 | 2 |
| Overall Study | Stem cell transplant | 6 | 6 | 4 | 3 |
| Overall Study | Treatment discontinued | 0 | 2 | 1 | 3 |
Baseline characteristics
| Characteristic | Romiplostim 100 µg | Romiplostim 300 µg | Romiplostim 700 µg | Romiplostim 1000 µg | Total |
|---|---|---|---|---|---|
| Age Continuous | 61.3 Year STANDARD_DEVIATION 6.2 | 58.1 Year STANDARD_DEVIATION 9.5 | 54.0 Year STANDARD_DEVIATION 16.3 | 59.9 Year STANDARD_DEVIATION 10.6 | 58.0 Year STANDARD_DEVIATION 11.5 |
| Race/Ethnicity, Customized Black or African American | 0 Participant | 0 Participant | 1 Participant | 1 Participant | 2 Participant |
| Race/Ethnicity, Customized Hispanic or Latino | 2 Participant | 1 Participant | 0 Participant | 0 Participant | 3 Participant |
| Race/Ethnicity, Customized White or Caucasian | 6 Participant | 10 Participant | 10 Participant | 8 Participant | 34 Participant |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 4 Participants | 5 Participants | 15 Participants |
| Sex: Female, Male Male | 5 Participants | 8 Participants | 7 Participants | 4 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 8 | 9 / 11 | 7 / 11 | 9 / 9 |
| serious Total, serious adverse events | 0 / 8 | 1 / 11 | 3 / 11 | 3 / 9 |
Outcome results
Primary
Change in Platelet Nadir
Change in platelet nadir from the previous qualifying cycle to the first treatment cycle.
Time frame: 32 weeks
Population: Efficacy Analysis Set, composed of all enrolled participants who received at least one dose of romiplostim, completed the first treatment cycle, and were not replaced per the protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Romiplostim 100 µg | Change in Platelet Nadir | 17.1 10^9/L | Standard Error 8.3 |
| Romiplostim 300 µg | Change in Platelet Nadir | 11.2 10^9/L | Standard Error 6.1 |
| Romiplostim 700 µg | Change in Platelet Nadir | 5.1 10^9/L | Standard Error 6.1 |
| Romiplostim 1000 µg | Change in Platelet Nadir | -5.2 10^9/L | Standard Error 7.8 |
p-value: 0.9654Satterhwaite t-test
p-value: 0.869Satterhwaite t-test
p-value: 0.7133Satterhwaite t-test
Secondary
Duration of Grade 3 or 4 Thrombocytopenia
Duration of grade 3 and/or 4 thrombocytopenia (\<50 x 10\^9/L and \<25 x 10\^9/L, respectively)
Time frame: 32 weeks
Population: Efficacy Analysis Set, composed of all enrolled participants who received at least one dose of romiplostim, completed the first treatment cycle, and were not replaced per the protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Romiplostim 100 µg | Duration of Grade 3 or 4 Thrombocytopenia | 3.9 Day | Standard Error 1.3 |
| Romiplostim 300 µg | Duration of Grade 3 or 4 Thrombocytopenia | 3.6 Day | Standard Error 0.9 |
| Romiplostim 700 µg | Duration of Grade 3 or 4 Thrombocytopenia | 6.0 Day | Standard Error 1.5 |
| Romiplostim 1000 µg | Duration of Grade 3 or 4 Thrombocytopenia | 8.3 Day | Standard Error 2.1 |
p-value: 0.091Satterhwaite t-test
p-value: 0.3Satterhwaite t-test
p-value: 0.881Satterhwaite t-test
Secondary
Percentage of Subjects Experiencing Grade 3 or 4 Thrombocytopenia
Percentage of subjects experiencing grade 3 and/or 4 thrombocytopenia (\<50 x 10\^9/L, and \<25 x 10\^9/L)
Time frame: 32 weeks
Population: Efficacy Analysis Set, composed of all enrolled participants who received at least one dose of romiplostim, completed the first treatment cycle, and were not replaced per the protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Romiplostim 100 µg | Percentage of Subjects Experiencing Grade 3 or 4 Thrombocytopenia | 62.5 Percentage of participants |
| Romiplostim 300 µg | Percentage of Subjects Experiencing Grade 3 or 4 Thrombocytopenia | 81.8 Percentage of participants |
| Romiplostim 700 µg | Percentage of Subjects Experiencing Grade 3 or 4 Thrombocytopenia | 80.0 Percentage of participants |
| Romiplostim 1000 µg | Percentage of Subjects Experiencing Grade 3 or 4 Thrombocytopenia | 88.9 Percentage of participants |
p-value: 0.294Fisher Exact
p-value: 0.608Fisher Exact
p-value: 0.603Fisher Exact
Secondary
Percentage of Subjects That Received Platelet Transfusions
Percentage of subjects that received platelet transfusions during the first romiplostim treatment cycle
Time frame: 32 weeks
Population: Efficacy Analysis Set, composed of all enrolled participants who received at least one dose of romiplostim, completed the first treatment cycle, and were not replaced per the protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Romiplostim 100 µg | Percentage of Subjects That Received Platelet Transfusions | 12.5 Percentage of participants |
| Romiplostim 300 µg | Percentage of Subjects That Received Platelet Transfusions | 0.0 Percentage of participants |
| Romiplostim 700 µg | Percentage of Subjects That Received Platelet Transfusions | 30.0 Percentage of participants |
| Romiplostim 1000 µg | Percentage of Subjects That Received Platelet Transfusions | 33.3 Percentage of participants |
p-value: 0.576Fisher Exact
p-value: 0.588Fisher Exact
p-value: 0.421Fisher Exact