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Pilot Phase II Trial on Safety and Activity of Secondary Prophylaxis With Romiplostim in Patients With Non-Hodgkin Lymphoma and Chemotherapy-induced Thrombocytopenia

Phase 2
18 Years
Open (Enrolling)
Non-Hodgkin Lymphoma

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Trial Information

Pilot Phase II Trial on Safety and Activity of Secondary Prophylaxis With Romiplostim in Patients With Non-Hodgkin Lymphoma and Chemotherapy-induced Thrombocytopenia

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.

Inclusion Criteria:

- 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
- Adequate bone marrow function (ANC >1.000; Hb >9,5 g/dL; PLT > 75.000).

Exclusion Criteria:

- 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.

- 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

- Pregnant or lactating females.

- Previous therapy with any TPO-mimetic or similar substances.

- Previous therapy supported by transplant of autologous or allogeneic stem cells

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Outcome Measure:


Outcome Description:

evaluation of safety, defined by the incidence of grade >/= 4 adverse events (NCI CTCAE v. 4.02 Dec 2009)

Outcome Time Frame:

participants will be followed for the duration of experimental treatment, an expected average of 6 months

Safety Issue:


Principal Investigator

Andrés JM Ferreri, MD

Investigator Role:

Study Chair

Investigator Affiliation:

San Raffaele Scientific Institute, Milano, Italy


Italy: Ethics Committee

Study ID:




Start Date:

November 2011

Completion Date:

September 2014

Related Keywords:

  • Non-Hodgkin Lymphoma
  • NHL
  • chemotherapy-induced grade-4 thrombocytopenia
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Thrombocytopenia