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Secondary Prophylaxis in Non-Hodgkin Lymphoma (NHL) and Chemotherapy-induced Thrombocytopenia (ProRom)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2012 by IRCCS San Raffaele.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Andres J. M. Ferreri, IRCCS San Raffaele
ClinicalTrials.gov Identifier:
NCT01516619
First received: January 8, 2012
Last updated: January 24, 2012
Last verified: January 2012

January 8, 2012
January 24, 2012
November 2011
November 2013   (final data collection date for primary outcome measure)
safety [ Time Frame: participants will be followed for the duration of experimental treatment, an expected average of 6 months ] [ Designated as safety issue: Yes ]
evaluation of safety, defined by the incidence of grade >/= 4 adverse events (NCI CTCAE v. 4.02 Dec 2009)
Same as current
Complete list of historical versions of study NCT01516619 on ClinicalTrials.gov Archive Site
activity [ Time Frame: From date of registration until the completion of chemotherapy treatment, an expected average of 6 months ] [ Designated as safety issue: Yes ]
activity defined by the incidence of grade 4 CIT (</= 25 x 10E9/L) per chemotherapy course during experimental treatment
Same as current
Not Provided
Not Provided
 
Secondary Prophylaxis in Non-Hodgkin Lymphoma (NHL) and Chemotherapy-induced Thrombocytopenia
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.

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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Non-Hodgkin Lymphoma
Drug: Romiplostim

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.

Other Names:
  • chemotherapy-induced thrombocytopenia
  • Nplate
Experimental: romiplostim
Intervention: Drug: Romiplostim
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
20
September 2014
November 2013   (final data collection date for primary outcome measure)

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 </= 3.
  • 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 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
Both
18 Years and older
No
Contact: Andrés JM Ferreri, MD +39022643 ext 7649 ferreri.andres@hsr.it
Contact: Silvia Govi, MD +39022643 ext 7612 govi.silvia@hsr.it
Italy
 
NCT01516619
ProRom
No
Andres J. M. Ferreri, IRCCS San Raffaele
Andres J. M. Ferreri
Amgen
Study Chair: Andrés JM Ferreri, MD San Raffaele Scientific Institute, Milano, Italy
IRCCS San Raffaele
January 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP