Clinical trial NCT00416624: Epoetin Alfa or Darbepoetin Alfa in Treating Patients With Anemia Caused by Chemotherapy
Official title: RC05CB A Pilot, Randomized Comparison of Standard Weekly Epoetin Alfa to Every-3-Week-Epoetin Alfa and Every 3-Week Darbepoetin Alfa
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anemia
Leukemia
Lymphoma
Lymphoproliferative Disorder
Multiple Myeloma and Plasma Cell Neoplasm
Precancerous Condition
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: unspecified adult solid tumor, protocol specific
extramedullary plasmacytoma
isolated plasmacytoma of bone
refractory multiple myeloma
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
Waldenstrom macroglobulinemia
post-transplant lymphoproliferative disorder
stage I adult T-cell leukemia/lymphoma
stage II adult T-cell leukemia/lymphoma
stage III adult T-cell leukemia/lymphoma
stage IV adult T-cell leukemia/lymphoma
recurrent adult T-cell leukemia/lymphoma
AIDS-related peripheral/systemic lymphoma
AIDS-related primary CNS lymphoma
angioimmunoblastic T-cell lymphoma
anaplastic large cell lymphoma
stage I cutaneous T-cell non-Hodgkin lymphoma
stage II cutaneous T-cell non-Hodgkin lymphoma
stage III cutaneous T-cell non-Hodgkin lymphoma
stage IV cutaneous T-cell non-Hodgkin lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
stage I mycosis fungoides/Sezary syndrome
stage II mycosis fungoides/Sezary syndrome
stage III mycosis fungoides/Sezary syndrome
stage IV mycosis fungoides/Sezary syndrome
recurrent mycosis fungoides/Sezary syndrome
stage I adult Hodgkin lymphoma
stage II adult Hodgkin lymphoma
stage III adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
recurrent adult Hodgkin lymphoma
adult grade III lymphomatoid granulomatosis
stage I adult Burkitt lymphoma
stage III adult Burkitt lymphoma
stage IV adult Burkitt lymphoma
noncontiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult lymphoblastic lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
noncontiguous stage II mantle cell lymphoma
noncontiguous stage II marginal zone lymphoma
noncontiguous stage II small lymphocytic lymphoma
contiguous stage II adult Burkitt lymphoma
contiguous stage II adult diffuse large cell lymphoma
contiguous stage II adult diffuse mixed cell lymphoma
contiguous stage II adult diffuse small cleaved cell lymphoma
contiguous stage II adult immunoblastic large cell lymphoma
contiguous stage II adult lymphoblastic lymphoma
contiguous stage II grade 1 follicular lymphoma
contiguous stage II grade 2 follicular lymphoma
contiguous stage II grade 3 follicular lymphoma
contiguous stage II mantle cell lymphoma
contiguous stage II marginal zone lymphoma
contiguous stage II small lymphocytic lymphoma
stage I adult diffuse large cell lymphoma
stage I adult diffuse mixed cell lymphoma
stage I adult diffuse small cleaved cell lymphoma
stage III adult diffuse large cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage I adult immunoblastic large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage I adult lymphoblastic lymphoma
stage III adult lymphoblastic lymphoma
stage IV adult lymphoblastic lymphoma
stage I grade 1 follicular lymphoma
stage I grade 2 follicular lymphoma
stage I grade 3 follicular lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage I mantle cell lymphoma
stage I marginal zone lymphoma
stage III mantle cell lymphoma
stage III marginal zone lymphoma
stage IV mantle cell lymphoma
stage IV marginal zone lymphoma
stage I small lymphocytic lymphoma
stage III small lymphocytic lymphoma
stage IV small lymphocytic lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult grade III lymphomatoid granulomatosis
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
adult acute lymphoblastic leukemia in remission
recurrent adult acute lymphoblastic leukemia
untreated adult acute lymphoblastic leukemia
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
refractory chronic lymphocytic leukemia
refractory hairy cell leukemia
progressive hairy cell leukemia, initial treatment
prolymphocytic leukemia
anemia
monoclonal gammopathy of undetermined significance
primary systemic amyloidosis
T-cell large granular lymphocyte leukemia
acute undifferentiated leukemia
mast cell leukemia
adult nasal type extranodal NK/T-cell lymphoma
untreated hairy cell leukemia
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-12-28
Enrollment: 239
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: RATIONALE: Epoetin alfa and darbepoetin alfa may cause the body to make more red blood cells. They are used to treat anemia caused by chemotherapy in patients with cancer.

PURPOSE: This randomized clinical trial is studying four different schedules of epoetin alfa or darbepoetin alfa to compare how well they work in treating patients with anemia caused by chemotherapy.

Detailed description: OBJECTIVES:

Primary

* Compare the relative efficacy of four different erythropoietic agent dosing schedules comprising epoetin alfa or darbepoetin alfa, in terms of the proportion of patients with chemotherapy-associated anemia who achieve a weekly and overall hematopoietic response.

Secondary

* Compare the effect of these regimens on the mean hemoglobin increment measured weekly from baseline to 15 weeks in patients with a baseline hemoglobin of less than or equal to 10.5 g/dL.
* Compare the time required to achieve hemoglobin levels within the goal range 11.0-12.0 g/dL in patients treated with these regimens.
* Compare the effect of these regimens on the proportion of patients requiring red blood cell transfusions and on the number of transfusions required.
* Compare the weekly change in hemoglobin in patients treated with these regimens.
* Compare the need for dose reduction in patients treated with these regimens.
* Compare the adverse event profiles of these regimens in these patients.
* Compare quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, unblinded, pilot study. Patients are stratified according to severity of anemia (mild \[hemoglobin ≥ 9.5 g/dL\] vs severe \[hemoglobin \< 9.5 g/dL\]), platinum-containing regimen (yes vs no), and tumor type (nonmyeloid hematologic malignancy vs solid tumor). Patients are randomized to 1 of 4 treatment arms.

* Arm I: Patients receive epoetin alfa subcutaneously (SC) on day 1. Treatment repeats weekly for up to 15 courses in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive epoetin alfa SC on day 1 (at a higher dose than in arm I). Treatment repeats every 3 weeks for up to 5 courses in the absence of disease progression or unacceptable toxicity.
* Arm III: Patients receive epoetin alfa SC on day 1 (at a higher dose than in arm II). Treatment repeats every 3 weeks for up to 5 courses in the absence of disease progression or unacceptable toxicity.
* Arm IV: Patients receive darbepoetin alfa SC on day 1. Treatment repeats every 3 weeks for up to 5 courses in the absence of disease progression or unacceptable toxicity.

Hemoglobin levels are monitored throughout the study on a weekly basis and before each drug dose is administered. Drug dosing is adjusted (e.g., held, reduced, resumed at a lower dose) as needed to maintain hemoglobin values within the desired ranges.

Quality of life is assessed at baseline and at weeks 4, 7, 10, 13, and 16.

After completion of study treatment, patients are followed at 30 days.

PROJECTED ACCRUAL: A total of 320 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of solid tumor or nonmyeloid hematologic malignancy (e.g., plasma cell dyscrasia or lymphoproliferative disorder)

  * No nonmelanomatous skin cancer
* Hemoglobin ≤ 10.5 g/dL
* Ferritin \> 20 ng/mL (i.e., not obviously iron deficient)
* Planning to receive ≥ 12 weeks of anticancer chemotherapy

  * Biological therapy (e.g., hypomethylating agents, monoclonal antibodies, or small molecule pathway inhibitors) with an individual or cumulative regimen incidence of grade 3 or 4 anemia \> 10% is considered chemotherapy for purposes of this study
* No known anemia secondary to any of the following:

  * Cyanocobalamin (vitamin B_12) or folic acid deficiency
  * Gastrointestinal bleeding within the past 2 weeks
  * Hemolysis
  * Myelodysplastic syndromes, myeloproliferative disorders, or acute myeloid leukemia
* No primary hematologic disorder causing chronic moderate to severe anemia (e.g., congenital dyserythropoietic anemia, homozygous hemoglobin S disease or compound heterozygous sickling states, or thalassemia major)

  * Carriers of these disease states allowed provided they are not anemic prior to cancer diagnosis

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* Life expectancy ≥ 6 months
* Not pregnant or nursing

  * No delivery of a baby of ≥ 18 weeks estimated gestational age within the past 3 months (90 days)
* Negative pregnancy test
* Fertile patients must use effective contraception
* Weight \> 40.0 kg and \< 150.0 kg
* No known hypersensitivity to epoetin alfa, darbepoetin alfa, mammalian-cell derived products, or human albumin
* No uncontrolled hypertension, defined as systolic blood pressure (BP) ≥ 180 mm Hg and/or diastolic BP ≥ 100 mm Hg, despite medical therapy
* No pulmonary emboli and/or deep vein thrombosis within the past 12 months

  * Patients actively receiving warfarin for a minimum of 4 weeks are exempted from this requirement
  * Prior superficial thrombophlebitis allowed
* No cerebrovascular accident, ischemic stroke, acute coronary syndrome (e.g., unstable angina or Q-wave or non-Q wave myocardial infarction), or other arterial or venous thrombotic events within the past 6 months
* No history of chronic hypercoagulable disorders (e.g., activated protein C resistance, anti-cardiolipin disorder, protein C deficiency, or protein S deficiency)

  * Patients receiving anticoagulation therapy (warfarin or acetylsalicyclic acid \[aspirin\] at a dose of ≥ 325 mg/day) for these conditions are eligible provided therapy is continued during the study period
* History of previously treated seizures allowed provided the patient has been seizure-free for a minimum of 3 months

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* More than 1 year since prior peripheral blood stem cell, bone marrow, or cord blood transplantation
* More than 14 days since prior red blood cell transfusion
* More than 14 days since prior major surgery, including, but not limited to, any of the following:

  * Amputation
  * Invasion of a body cavity or of the central nervous system using a scalpel, saw, or laser cutting tool
  * Resection of a body part (or parts), whether solid or liquid tissue or both, that includes ≥ 1% of a patient's preoperative weight
  * The following are not considered major surgery:

    * Diagnostic/therapeutic thoracentesis or paracentesis
    * Diagnostic skin biopsy
    * Digit or fingernail/thumbnail resection or laceration repair under local anesthesia
    * Diagnostic fat aspiration
    * Otic irrigation to remove cerumen impaction
    * Tympanocentesis
    * Uncomplicated dental extraction
    * Uncomplicated tonsillectomy
    * Laser corneal remodeling for refraction purposes
    * Cosmetic or therapeutic eyelid surgery
    * Bone marrow aspiration and biopsy
* More than 10 weeks since prior darbepoetin alfa, epoetin alfa, or any investigational form of erythropoietin (e.g., gene-activated erythropoietin or novel erythropoiesis stimulating protein)
* No planned stem cell transplantation within the next 4 months (18 weeks)

Primary outcomes:
measure: The Percentage of Participants Who Exhibit a Hematopoietic Response
timeFrame: 20 weeks
Secondary outcomes:
measure: Weekly Change in Hemoglobin Levels
timeFrame: Baseline and Week 4, 7, 10, 13, 16
measure: Time Required to Achieve Hemoglobin Levels >= 11.5 g/dL
timeFrame: 16 weeks
measure: Mean Hemoglobin Change From Week 1 to Week 16
timeFrame: Week 1 and Week 16
measure: The Percentage of Participants Requiring Red Blood Cell (RBC) Transfusions
timeFrame: 16 weeks
measure: The Total RBC Transfusion Needed
timeFrame: 16 weeks
measure: The Percentage of Participants With Dose Omitted Due to Hematologic Reason
timeFrame: 16 Weeks
measure: The Percentage of Participants Reported Grade 3 or 4 Adverse Events
timeFrame: 16 weeks
measure: Quality of Life as Measured by Functional Assessment of Cancer Therapy Scales for Anemia (FACT-AN) Over All Follow-up Evaluations
timeFrame: Weeks 4, 7, 10, 13 and 16
measure: Quality of Life as Measured by Linear Analogue Self Assessment Over All Follow-up Evaluation
timeFrame: Weeks 4, 7, 10, 13 and 16
measure: Quality of Life as Measured by Brief Fatigue Inventory Overall All Follow-up Evaluations
timeFrame: Weeks 4, 7, 10, 13 and 16
measure: Quality of Life as Measured by Symptom Distress Scale (SDS) Over All Follow-up Evaluations
timeFrame: Weeks 4, 7, 10, 13 and 16
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Charles L. Loprinzi, M.D.
role: STUDY_CHAIR
References: