Using Romiplostim to Treat Low Platelet Counts During Chemotherapy in Patients with Lymphoma
This phase II trial studies the effects of romiplostim in treating low platelet counts during chemotherapy in patients with lymphoma. Platelets are made when the liver produces a hormone that travels to the bone marrow. Once the hormone is in the bone marrow, it finds a specific protein on the surface of cells called megakaryocytes, which are responsible for making platelets. The more this hormone binds to the megakaryocytes, the more platelets are made. Romiplostim acts like the hormone produced in the liver because it finds the same proteins on the surface of megakaryocytes and helps increase the production of platelets. Romiplostim may prevent the need for dose delays and dose reductions during chemotherapy treatment and avoid the need for platelet transfusions.
Inclusion Criteria
- Adult patients >= 18 years old diagnosed with any type of lymphoma
- Receiving chemotherapy-based treatment known to cause thrombocytopenia. Eligibility is limited to regimens with a 21- day cycle. Previous single-agent anti CD20 antibody or radiotherapy will not count as a line of treatment. Eligible regimens include those based on a platinum backbone (e.g. ifosfamide-carboplatin-etoposide [ICE], dexamethasone/cytarabine/oxaliplatin [DHAX], dexamethasone-high dose araC-Platinol [DHAP], gemcitabine-oxaliplatin [GemOx], gemcitabine/dexamethasone/cisplatin [GDP], etoposide-Solumedrol-high dose ara-C-Platino; [ESHAP]), those based on a doxorubicin backbone (e.g. cyclophosphamide/doxorubicin/prednisone/vincristine [CHOP], cyclophosphamide/pegylated liposomal doxorubicin/vincristine/prednisone [CDOP], hyperfractionated cyclophosphamide-vincristine-Adriamycin-dexamethasone [HyperCVAD], bleomycin-etoposide-Adriamycin-cyclophosphamide-Oncovin-procarbazine-prednisone [BEACOPP]) or on a high-dose cytarabine backbone (e.g. HiDAC). Of note, treatment programs which involve sequential administration of two or more regimens (e.g. CHOP->ICE or CHOP-DHAX) are eligible as long as the patient is planned for at least two more cycles of the regimen on which the CIT was initially observed
- History of a severe treatment-related thrombocytopenia during the most recent cycle of treatment, as defined by one or more of the following criteria: * PLT < 50,000 on day 1 (- 2 days) of the subsequent treatment cycle * Grade 4 thrombocytopenia, defined as PLT < 25,000 cells/mcl and/or transfusion for thrombocytopenia or bleeding. Need for PLT transfusion in order to meet minimal PLT criteria for invasive procedures will not count for eligibility
- Patient is planned for at least one more cycle of chemotherapy
- Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 (Karnofsky >= 50%)
- Absolute neutrophil count >= 1,000/mcL (on day 1 of the prior cycle) – use of granulocyte colony-stimulating factor (gCSF) is acceptable for eligibility
- Hemoglobin >= 7 g/dL - transfusion support is acceptable for eligibility (on day 1 of the prior cycle)
- Total bilirubin =< 3 x the institutional upper limit of normal (ULN) (on day 1 of the prior cycle)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x institutional upper limit of normal (on day 1 of the prior cycle)
- Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral therapy with undetectable viral load are eligible for this trial, provided there are no anticipated interactions between antiretroviral treatment and the study drug
- Women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
- Ability to understand and the willingness to sign a written informed consent document prior to participation in the study and any related procedures being performed. Legally Authorized Representatives are permitted
Exclusion Criteria
- History of or concurrent hematological malignancy other than lymphoma (acute or chronic leukemia, myelodysplastic syndrome [MDS], myeloproliferative neoplasm, multiple myeloma). Patient with composite/concurrent lymphoma or Richter’s transformation are eligible
- History of allogeneic hematopoietic stem cell transplantation (SCT). Patients with a prior autologous SCT or chimeric antigen receptor (CAR)-T treatment are eligible
- Patients with history of symptomatic venous thrombotic event (VTE), such as deep vein thrombosis (DVT) or pulmonary embolism (PE) who is unable to tolerate anticoagulation. Patients who have completed their indicated course of anticoagulation prior to enrollment or are tolerating ongoing anticoagulation are eligible. Patients with VTE associated with central venous catheter are eligible
- Patients with history of symptomatic arterial thrombotic events such as myocardial infarction, ischemia cerebral vascular accident, or transient ischemic attack within 4 months prior to enrollment
- Patients who have thrombocytopenia related to pre-existing idiopathic thrombocytopenic purpura (ITP)
- Major surgery within 26 days prior to enrollment, or minor surgery within 3 days prior to enrollment
- Solid-tumor malignancy metastatic or locally-advanced unresectable within the last 5 years that could adversely affect subject safety or longevity, create the potential for drug-drug interactions, or compromise the interpretation of study results
- Concurrent therapy with other investigational agents
- Within 4 months prior to enrollment, any history of active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, uncontrolled arrhythmias, clinically significant electrocardiogram (ECG) abnormalities, screening ECG with corrected QT (QTc) interval of > 470 msec, pericardial disease, or myocardial infarction
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, renal failure requiring hemodialysis, or psychiatric illness/social situations that would limit compliance with study requirements. These include abnormal laboratory values, that could cause unacceptable safety risks or compromise compliance with the protocol
- Patients are excluded from this study if pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 180 days after the last dose of trial treatment
- Patient has acute viral hepatitis (typically defined by elevated AST/ALT), or a history of chronic or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (hepatitis B virus core antibody [HBcAb] or hepatitis B virus surface antigen [HBsAg] positive and detectable serum/plasma HBV deoxyribonucleic acid [DNA], or HCV antibody [Ab] positive and detectable serum/plasma HCV ribonucleic acid [RNA])
- Patients with any significant history of non-compliance to medical regimens or unwilling or unable to comply with the instructions given to him/her by the study staff
Additional locations may be listed on ClinicalTrials.gov for NCT04673266.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVE:
I. To assess the efficacy of romiplostim in reducing chemotherapy induced thrombocytopenia (CIT) associated complications that would otherwise mandate dose delays or dose reductions in patients with severe CIT on a prior cycle of lymphoma chemotherapy manifested by a composite endpoint of platelets (PLT) < 50,000 cells/mcl on the first day of the subsequent cycle, grade 4 thrombocytopenia and/or need for PLT transfusions for thrombocytopenia or bleeding at any point during the treatment cycle.
SECONDARY OBJECTIVES:
I. To assess the safety and tolerability of romiplostim in patients with lymphoma and severe CIT secondary to chemotherapy.
II. To evaluate the composite outcome during cycle 2 (cycle 2 day 1 [C2D1] to cycle 2 day 21 [C2D21]).
III. To evaluate the persistence (in days) of dose delay in subsequent chemotherapy cycles (number of days PLT < 50,000 cells/mcl).
IV. To evaluate the persistence (in days) of thrombocytopenia (PLT < 100,000 cells/mcl).
EXPLORATORY OBJECTIVE:
I. Evaluate the incidence and persistence (in days) of anemia (hemoglobin [Hgb] =< 10 g/dL) and neutropenia (absolute neutrophil count [ANC] < 1000 cell/mcl) in patients with lymphoma treated with romiplostim for severe CIT.
OUTLINE:
Beginning the same day as chemotherapy, patients receive romiplostim subcutaneously (SC) once weekly (QW). Treatment repeats every 21 days for 2-5 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 14 and 30 days, and up to 12 weeks.
Trial PhasePhase II
Trial Typesupportive care
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorZachary D. Epstein-Peterson
- Primary ID20-492
- Secondary IDsNCI-2020-13829
- ClinicalTrials.gov IDNCT04673266