Non-Hodgkin LymphomaPhase 2ProRomNCT01516619
Secondary Prophylaxis in Non-Hodgkin Lymphoma (NHL) and Chemotherapy-induced Thrombocytopenia
A Phase 2 study testing Romiplostim in people with Non-Hodgkin Lymphoma, run by Andres J. M. Ferreri at 1 site in Italy.
Trial summary
This is a monocentric, prospective phase II trial addressing safety and capability to prevent grade-4 Chemotherapy-induced Thrombocytopenia (CIT) of romiplostim in patients with NHL. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Hodgkin Lymphoma
- What is being tested?
- Romiplostim
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteItaly
- Study dates
- Nov 2011to Nov 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient with NHL of any histotype, both at diagnosis or at relapse, who experienced grade 4 CIT after the first course of chemotherapy containing high doses of methotrexate, cytarabine, cisplatin, cyclophosphamide and/or ifosfamide, and/or conventional doses of anthracyclines or purine analogs, with or without rituximab. The same type of chemotherapy where the grade 4 CIT occurred will be continued at the same planned doses for a maximum of 8 courses.
- ECOG performance status score </= 3.
- Adequate bone marrow function (ANC >1.000; Hb >9,5 g/dL; PLT > 75.000).
Who cannot join
- Patients eligible for high-dose chemotherapy, where stem cell support is planned.
- Thrombotic events in the previous 5 years before enrolment.
- Other malignancies diagnosed in the previous 5 years before enrolment.
- Severe concomitant illnesses/medical conditions (e.g. impaired respiratory and/or cardiac function, uncontrolled diabetes mellitus).
- Active infectious disease.
- Impaired liver function (bilirubin >2 x upper normal limit; ALT/AST/GGT > 3 x upper normal limit) at one month from salvage chemotherapy conclusion.
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- Impaired renal function (creatinine clearance <50 ml/min) at one month from salvage chemotherapy conclusion.
- Non-cooperative behavior or non-compliance.
- Psychiatric diseases or conditions that might impair the ability to give informed consent.
- Pregnant or lactating females.
- Previous therapy with any TPO-mimetic or similar substances.
- Previous therapy supported by transplant of autologous or allogeneic stem cells
Trial locations and contacts
1 site in 1 country.
Italy1 site
Dip. Oncoematologia - Fondazione Centro San Raffaele del Monte Tabor
Milan
About this study
Official title: Pilot Phase II Trial on Safety and Activity of Secondary Prophylaxis With Romiplostim in Patients With Non-Hodgkin Lymphoma and Chemotherapy-induced Thrombocytopenia
This is a monocentric, prospective phase II trial addressing safety and capability to prevent grade-4 Chemotherapy-induced Thrombocytopenia (CIT) of romiplostim in patients with NHL.
Read the detailed description
High-dose chemotherapy followed by autologous stem cell transplant is considered standard of care for patients with relapsed and/or refractory aggressive lymphomas. High-dose chemotherapy, with or without ASCT, may also be used as upfront chemotherapy according to lymphoma histotype (e.g. primary central nervous system lymphomas, mantle cell lymphomas), advanced stage disease, extranodal involvement, and high IPI. Chemotherapy-induced myelosuppression results in various degrees of neutropenia, anemia, and thrombocytopenia and related complications can lead to hospitalization, impaired quality of life, death, and increased healthcare costs.
While myeloid growth factors have reduced neutropenia and the incidence of neutropenic fever, and erythropoietic agents have reduced anemia and transfusions, chemotherapy-induced thrombocytopenia (CIT) still remains an unmet treatment need.
Thrombocytopenia is significantly associated with increased bleeding risk, platelet transfusions need, chemotherapy dose reductions and treatment delays, which usually compromise therapeutic efficacy. Platelet transfusions are also limited by cost, supply, and associated risks, such as transfusion reactions, transmission of infection, alloimmunization and platelet refractoriness. Alternative strategies are evaluating pharmacologic options to stimulate platelet production and to overcome CIT.
The predominant reason for a low platelet count in cancer patients receiving chemotherapy is a deficiency in platelet production. Megakaryopoiesis, the process of development of mega-karyocytes and production of platelets, involves a highly complex cascade of events, from differentiation of immature progenitors to maturation of megakaryocytes and release of platelets into the bone marrow sinusoids. Cytokines present within specialized bone marrow niches contribute to survival, proliferation, and differentiation of megakaryocytes. In addition to TPO, an essential growth factor for platelet production, there are several other growth factors and cytokines, such as IL-1, IL-3, IL-6, IL-11, and SCF, that contribute towards megakaryopoiesis at different stages of development and maturation. In the last decade, a number of these cytokines have been evaluated for the prevention and treatment of thrombocytopenia. Unfortunately, none has yet provided a commercially available agent with a high therapeutic index.
Despite very promising thrombopoietic activity, the clinical development of first-generation recombinant TPOs was halted due to immunogenicity concerns. This led to the development of TPO agonists with no homology to TPO that can bind the TPO receptors and activate signal-ling, leading to increase in platelet production.
- Conditions
- Non-Hodgkin Lymphoma
- Being tested
- Romiplostim
- Keywords
- NHL, chemotherapy-induced grade-4 thrombocytopenia
- Medical subject headings
- Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RomiplostimDrug
Also called chemotherapy-induced thrombocytopenia, Nplate
Romiplostim will be administered subcutaneously at a dose of 250 μg on the 1st, 3rd and 5th days after the last day of chemotherapy delivery and, then, every two days until the achievement of 75.000 plt/μL.
In the case of unsuccessful use of romiplostim after the second chemotherapy course, dose escalation to 500 μg/day, with the same above-mentioned schedule, will be indicated after the third course and for all the further courses, with a maximum of 8.
| Study group | Role | What they receive |
|---|---|---|
| romiplostim | Experimental | Not described Receives: Drug: Romiplostim |
What is being measured
The primary outcome is the main question the study is designed to answer.
safety
evaluation of safety, defined by the incidence of grade >/= 4 adverse events (NCI CTCAE v. 4.02 Dec 2009)
Measured: participants will be followed for the duration of experimental treatment, an expected average of 6 months
Secondary outcomes (1)
activity
activity defined by the incidence of grade 4 CIT (</= 25 x 10E9/L) per chemotherapy course during experimental treatment
Measured: From date of registration until the completion of chemotherapy treatment, an expected average of 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2012 (estimated)
- Study startNov 2011
- Primary completionNov 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Hodgkin LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Andres J. M. Ferreri
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen
- Responsible party
- Sponsor-investigator, Andres J. M. Ferreri, IRCCS San Raffaele
- Investigators
- Andrés JM Ferreri, MD, Study chair, San Raffaele Scientific Institute, Milano, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01516619
- Sponsor's protocol ID
- ProRom
- Acronym
- ProRom
- Status last verified
- Aug 2022
- First submitted
- 8 Jan 2012
- Last updated
- 12 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Phase II Trial on Safety and Activity of Secondary Prophylaxis With Romiplostim in Patients With Non-Hodgkin Lymphoma and Chemotherapy-induced Thrombocytopenia
- ClinicalTrials.gov ID
- NCT01516619
- Acronym / sponsor ID
- ProRom / ProRom
- Conditions
- Non-Hodgkin Lymphoma
- Keywords
- NHL, chemotherapy-induced grade-4 thrombocytopenia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Andres J. M. FerreriUniversity, hospital or other
- Collaborators
- Amgen
- Study start
- Nov 2011 (actual)
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 25 Jan 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a monocentric, prospective phase II trial addressing safety and capability to prevent grade-4 Chemotherapy-induced Thrombocytopenia (CIT) of romiplostim in patients with NHL.
Detailed description
High-dose chemotherapy followed by autologous stem cell transplant is considered standard of care for patients with relapsed and/or refractory aggressive lymphomas. High-dose chemotherapy, with or without ASCT, may also be used as upfront chemotherapy according to lymphoma histotype (e.g. primary central nervous system lymphomas, mantle cell lymphomas), advanced stage disease, extranodal involvement, and high IPI. Chemotherapy-induced myelosuppression results in various degrees of neutropenia, anemia, and thrombocytopenia and related complications can lead to hospitalization, impaired quality of life, death, and increased healthcare costs.
While myeloid growth factors have reduced neutropenia and the incidence of neutropenic fever, and erythropoietic agents have reduced anemia and transfusions, chemotherapy-induced thrombocytopenia (CIT) still remains an unmet treatment need.
Thrombocytopenia is significantly associated with increased bleeding risk, platelet transfusions need, chemotherapy dose reductions and treatment delays, which usually compromise therapeutic efficacy. Platelet transfusions are also limited by cost, supply, and associated risks, such as transfusion reactions, transmission of infection, alloimmunization and platelet refractoriness. Alternative strategies are evaluating pharmacologic options to stimulate platelet production and to overcome CIT.
The predominant reason for a low platelet count in cancer patients receiving chemotherapy is a deficiency in platelet production. Megakaryopoiesis, the process of development of mega-karyocytes and production of platelets, involves a highly complex cascade of events, from differentiation of immature progenitors to maturation of megakaryocytes and release of platelets into the bone marrow sinusoids. Cytokines present within specialized bone marrow niches contribute to survival, proliferation, and differentiation of megakaryocytes. In addition to TPO, an essential growth factor for platelet production, there are several other growth factors and cytokines, such as IL-1, IL-3, IL-6, IL-11, and SCF, that contribute towards megakaryopoiesis at different stages of development and maturation. In the last decade, a number of these cytokines have been evaluated for the prevention and treatment of thrombocytopenia. Unfortunately, none has yet provided a commercially available agent with a high therapeutic index.
Despite very promising thrombopoietic activity, the clinical development of first-generation recombinant TPOs was halted due to immunogenicity concerns. This led to the development of TPO agonists with no homology to TPO that can bind the TPO receptors and activate signal-ling, leading to increase in platelet production.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| romiplostim | Experimental | Drug: Romiplostim |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patient with NHL of any histotype, both at diagnosis or at relapse, who experienced grade 4 CIT after the first course of chemotherapy containing high doses of methotrexate, cytarabine, cisplatin, cyclophosphamide and/or ifosfamide, and/or conventional doses of anthracyclines or purine analogs, with or without rituximab. The same type of chemotherapy where the grade 4 CIT occurred will be continued at the same planned doses for a maximum of 8 courses.
- ECOG performance status score </= 3.
- Adequate bone marrow function (ANC >1.000; Hb >9,5 g/dL; PLT > 75.000).
Key exclusion criteria (12 listed)
- Patients eligible for high-dose chemotherapy, where stem cell support is planned.
- Thrombotic events in the previous 5 years before enrolment.
- Other malignancies diagnosed in the previous 5 years before enrolment.
- Severe concomitant illnesses/medical conditions (e.g. impaired respiratory and/or cardiac function, uncontrolled diabetes mellitus).
- Active infectious disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RomiplostimAlso: chemotherapy-induced thrombocytopenia, NplateRomiplostim will be administered subcutaneously at a dose of 250 μg on the 1st, 3rd and 5th days after the last day of chemotherapy delivery and, then, every two days until the achievement of 75.000 plt/μL. In the case of unsuccessful use of romiplostim after the second chemotherapy course, dose escalation to 500 μg/day, with the same above-mentioned schedule, will be indicated after the third course and for all the further courses, with a maximum of 8. | Drug | romiplostim |
Primary outcome
safety
Time frame: participants will be followed for the duration of experimental treatment, an expected average of 6 months
evaluation of safety, defined by the incidence of grade >/= 4 adverse events (NCI CTCAE v. 4.02 Dec 2009)
1 secondary outcome
activity
Time frame: From date of registration until the completion of chemotherapy treatment, an expected average of 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrés JM Ferreri, MD study chair
San Raffaele Scientific Institute, Milano, Italy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Romiplostim in people with Non-Hodgkin Lymphoma, run by Andres J. M. Ferreri at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
safety (time frame: participants will be followed for the duration of experimental treatment, an expected average of 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2022.