Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double-Blind, Placebo-Controlled Study of Darbepoetin Alfa for the Treatment of Anemia in Subjects With Non-Myeloid Malignancy Receiving Multicycle Chemotherapy
Brief Summary: The purpose of this study is to compare the effect of darbepoetin alfa against placebo for the treatment of anemia in subjects with non-myeloid malignancies receiving multicycle chemotherapy.


Options:
A: Inclusion Criteria:

MDS defined as

* RCMD, RA with or without ring sideroblasts
* RAEB 1, or CMML 1, if WBC \< 13 G /l according to the WHO classification
* with a low or int-1 IPSS score AND
* primary or secondary resistance to epoetin alpha/ beta (\> 60000 U/w) or darbepoetin (\> 250ug/w), administered for at least 12 weeks
* requirement of RBC transfusions \> 4 U in the previous 8 weeks
* Aged 18 years or more
* Adequate contraception, if relevant
* Negative pregnancy test if relevant
* Written Informed consent
* Ability to participate to a clinical trial and adhere to study procedures
* Health insurance

Exclusion Criteria:

* Therapy-related MDS (after chemo- or radiotherapy for a previous neoplasm or immune disorder)
* Patients with a planned allogeneic bone marrow transplantation
* Creatininemia \>1.5 upper normal value or estimated Ccr less than 30ml/mn
* ALAT and ASAT \>2.5 upper normal value
* Bilirubin \>2N, except unconjugated hyperbilirubinemia due to MDS-related dyserythropoiesis
* Heart failure NYHA \> II
* Known allergy to mannitol
* Other tumor, unstable for the last three years, except in situ uterine carcinoma or basal skin tumor
* ECOG \> 2
* Life expectancy less than 3 months
B: Inclusion Criteria:

* Diagnosis of CLL according to the National Cancer Institute (NCI)/Internal Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria or small lymphocytic lymphoma (SLL) according to the World Health Organization (WHO) criteria; this includes previous documentation of:

  * Biopsy-proven small lymphocytic lymphoma or
  * Diagnosis of CLL according to the NCI/IWCLL criteria as evidenced by all of the following:

    * Peripheral blood lymphocyte count of greater than 5 x 10\^9/L
    * Immunophenotype consistent with CLL defined as:

      * The predominant population of lymphocytes share both B-cell antigens (cluster of differentiation \[CD\]19, CD20 \[typically dim expression\], or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc)
      * Clonality as evidenced by kappa or lambda light chain restriction (typically dim immunoglobulin expression)
  * Negative FISH analysis for t(11;14)(immunoglobulin heavy locus \[IgH\]/cyclin D1 \[CCND1\]) on peripheral blood or tissue biopsy (e.g. marrow aspirate) or negative immunohistochemical stains for cyclin D1 staining on involved tissue biopsy (e.g. marrow aspirate or lymph node biopsy)
* No prior chemotherapy, Bruton's tyrosine kinase (BTK) inhibitor therapy, or monoclonal anti-body therapy for treatment of CLL or SLL
* Has met at least one of the following indications for treatment:

  * Evidence of progressive marrow failure as manifested by the development of worsening anemia (hemoglobin \[Hg\] \< 11 g/dl) and/or thrombocytopenia (platelets \< 100 x 10\^9/L)
  * Symptomatic or progressive lymphadenopathy, splenomegaly, or hepatomegaly
  * One or more of the following disease-related symptoms:

    * Weight loss \>= 10% within the previous 6 months
    * Grade 2 or 3 fatigue attributed to CLL
    * Fevers \> 100.5 Fahrenheit (F) for 2 weeks without evidence of infection
    * Clinically significant night sweats without evidence of infection
  * Progressive lymphocytosis (not due to the effects of corticosteroids) with an increase of \> 50% over a two-month period or an anticipated doubling time of less than six months
* ECOG performance status between 0-2
* Life expectancy of \>= 12 months
* Ability to tolerate FCR based therapy
* No deletion of 17p13 on cytogenetic analysis by FISH
* Glomerular filtration rate (GFR) \> 40 mL/minute as calculated by the Cockcroft-Gault formula (obtained =\< 14 days prior to registration)
* Total bilirubin =\< 2.5 x upper limit of normal (ULN) (obtained =\< 14 days prior to registration) unless due to Gilbert's disease; for those with a total bilirubin \> 2.5 x ULN, a direct bilirubin should be performed and must be \< 1.5 mg/dL for Gilbert's to be diagnosed

  * If value is higher due to hepatic involvement by CLL, patient is eligible
* Serum glutamic oxaloacetic transaminase (SGOT) (aspartate transaminase \[AST\])/serum glutamate-pyruvate transaminase (SGPT) (alanine transaminase \[ALT\]) =\< 3.0 x the institutional ULN (obtained =\< 14 days prior to registration)

  * If value is higher due to hepatic involvement by CLL, patient is eligible
* Prothrombin time (PT)/international normalized ratio (INR) \< 1.5 ULN and partial thromboplastin time (PTT) (activated partial thromboplastin time \[aPTT\]) \< 1.5 X ULN (obtained =\< 14 days prior to registration)

  * If value is higher due to hepatic involvement by CLL, patient is eligible
* No active hemolytic anemia requiring immunosuppressive therapy or other pharmacologic treatment; patients who have a positive Coombs test but no evidence of hemolysis are NOT excluded from participation
* No current use of corticosteroids; EXCEPTION: low doses of steroids (\< 10 mg of prednisone or equivalent dose of other steroid) used for treatment of non-hematologic medical condition (e.g. chronic adrenal insufficiency) is permitted
* No previous use of corticosteroids for autoimmune complications that have developed since the initial diagnosis of CLL; prior use of corticosteroids for reasons other than treatment of autoimmune complications is allowed
* No other active primary malignancy (other than non-melanomatous skin cancer or carcinoma in situ of the cervix) requiring treatment or limiting expected survival to =\< 2 years; NOTE: if there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy for their cancer)
* Able to adhere to the study visit schedule and other protocol requirements
* No major surgery within the last 4 weeks (28 days) of first dose of study drug or minor surgery within 3 days of first dose of study drug
* No radiation therapy =\< 4 weeks prior to registration
* Patients with human immunodeficiency virus (HIV) infection may be eligible provided they meet the following criteria:

  * CD4-positive cell count \>= lower limit of institutional normal
  * HIV viral load \< 10,000 copies HIV ribonucleic acid (RNA)/mL (if not on anti-HIV therapy) OR \< 50 copies HIV RNA/mL (if on anti-HIV therapy)
  * No evidence of hepatitis B or C infection
  * No evidence of resistant strains of HIV
  * No history of acquired immune deficiency syndrome (AIDS)-defining condition
* Patients must not have any of the following conditions:

  * Congestive heart failure or New York Heart Association Functional Classification III or IV congestive heart failure
  * History of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to registration
  * Recent infections requiring systemic treatment; need to have completed anti-biotic therapy \> 14 days before the first dose of study drug
  * Cerebral vascular accident or intracranial bleed within the last 6 months
  * Infection with known chronic, active hepatitis C
  * Serologic status reflecting active hepatitis B or C infection; patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment (PCR positive patients will be excluded)
* Patients are not eligible if they require treatment with a strong cytochrome P450 (CYP) family 3, subfamily A (3A) inhibitor
* Patients may not be on any other investigational agents
* Patients may not have received warfarin or another vitamin K antagonist in the preceding 30 days
* Women must not be pregnant or breast-feeding since this study involves an investigational agent whose genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are unknown; female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to registration to rule out pregnancy; female patients who are of non-reproductive potential are those who are post-menopausal by history (i.e. no menses for \>= 1 year); OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy)
* Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for 90 days after the last dose of study drug
* Patient must be able to swallow capsules and not have the following conditions:

  * Disease significantly affecting gastrointestinal function
  * Resection of the stomach or small bowel
  * Symptomatic inflammatory bowel disease
  * Ulcerative colitis
  * Partial or complete bowel obstruction
* Patient must not be on any other systemic immunosuppressant therapy other than corticosteroids within 28 days of the first dose of study drug
* Patient must not be vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug
* Patient must not have any known bleeding disorders (e.g., von Willebrand's disease) or hemophilia
* Patient must not have currently active, clinically significant hepatic impairment (\>= moderate hepatic impairment according to the NCI/Child Pugh)
C: Inclusion Criteria:

* Age \>= 18 years
* NOTE: Results of the bone marrow biopsy and aspirate as well as cytogenetics are mandatory to register subjects onto study, which are indispensable to determine International Prognostic Scoring System (IPSS) category needed for eligibility; please note that it is not necessary to wait for the week 16, week 32, or week bone marrow and cytogenetic results prior to starting the next cycle unless deemed necessary by the treating physician; one example of this exception can include if the subject shows signs of progression, such as increased peripheral blood blast percentage; at that juncture, the treating physician may prefer to await the results prior to starting a new cycle; if a cycle is started, and based on the bone marrow results it is felt by the treating physician that the subject should not continue on treatment, please be sure to note this information on the case report forms at end of treatment
* Patient must have documented diagnosis of MDS lasting at least three months (MDS duration \>= 3 months) according to World Health Organization (WHO) criteria or non-proliferative chronic myelomonocytic leukemia (CMML) (white blood cell \[WBC\] \< 12,000/mcL)
* Patient must have International Prognostic Scoring System (IPSS) categories of low- or intermediate-1-risk disease; patients must have IPSS score determined by cytogenetic analysis prior to randomization; patients must have cytogenetic analysis done (to calculate IPSS); if the current bone marrow biopsy is a dry tap, patients with cytogenetic failure and \< 10% marrow blasts will be eligible; subjects with cytogenetic failure must have previous cytogenetic results (fluorescence in situ hybridization \[FISH\] is not a substitute) within the last 6 months post last type of MDS treatment (in this case, not referring to growth factors as type of MDS treatment)
* Must have symptomatic anemia untransfused with hemoglobin \< 9.5 g/dL =\< 8 weeks prior to randomization or with red blood cells (RBC) transfusion dependence (i.e., \>= 2 units/month) confirmed for =\< 8 weeks before randomization

  * NOTE: For non-transfusion dependent patients (i.e., receiving \< 2 units/4 weeks x 8 weeks pre-study) who receive periodic transfusions, the mean 8 week pre-transfusion hemoglobin should be used to determine protocol eligibility and response reference
  * For non-transfusion dependent patients, a minimum of 2 pre-transfusion or un-transfused hemoglobin values are required
* Applies only for patients without the deletion 5q 31.1; patients must have failed treatment with an erythropoietic growth factor, or have a low probability of response to rhu-erythropoietin; patients with low probability of response to rhu-erythropoietin or prior erythropoietin failures are defined as follows:

  * Prior erythropoietin failure-requires a minimum trial of \>= 40,000 units epoetin alfa/week x 8 weeks or equivalent dose of darbepoetin alfa for 8 weeks with failure to achieve transfusion independence in dependent patients or a failure to achieve a \>= 2 g rise in hemoglobin sustained for \>= 4 weeks in non-transfusion dependent patients
  * Low erythropoietin response profile-rhu-erythropoietin and epoetin alfa-naïve patients receiving \>= 2U packed (p)RBC/month for a minimum of 8 weeks, and serum erythropoietin \> 500 mU/mL in the 8 weeks prior to randomization for a hemoglobin \< 9.5 g/dL
* Patients must be off all non-transfusion therapy for MDS for 28 days prior to initiation of study treatment, including all types of growth factors; patients may receive hydrocortisone prophylactically to prevent transfusion reactions
* Patients must have a serum erythropoietin level documented before randomization and =\< 56 days before day 1 of study treatment; NOTE: hemoglobin must be \< 9.5 g/dL at time that serum erythropoietin is drawn
* Effective contraception must be used by patients participating in lenalidomide therapy, and all patients must agree to counseling by a trained counselor every 28 days about pregnancy precautions and risks of fetal exposure; females of childbearing potential (FCBP) must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control: one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before starting lenalidomide, during lenalidomide therapy, during dose interruptions, and for at least 28 days following discontinuation of lenalidomide therapy; females of childbearing potential should be referred to a qualified provider of contraceptive methods, if needed; males receiving lenalidomide must agree to use a latex condom during any sexual contact with females of childbearing potential even if they have undergone a successful vasectomy
* Platelet count \>= 50,000/mcL (50 x 10\^9/L) without platelet transfusion (within 56 days prior to randomization)
* Absolute neutrophil count (ANC) \>= 500 cells/mcL (0.5 x 10\^9/L); hence ANC must be \>= 500/mcL without myeloid growth factor support (within 56 days prior to randomization)
* Serum creatinine =\< 1.5 times upper limit of normal (ULN) (within 56 days prior to randomization)
* Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) or serum glutamate pyruvate transaminase (SGPT)/alanine aminotransferase (ALT) =\< 2.0 x ULN (within 56 days prior to randomization)
* Serum total bilirubin \< 3.0 mg/dL (within 56 days prior to randomization)
* Inclusion criteria for crossover registration from Arm A (lenalidomide alone) to Arm B (lenalidomide and epoetin alfa):
* Patients must have completed 16 weeks of monotherapy with lenalidomide
* Patients must show failure to achieve MER (major erythroid response) or have achieved MER but relapsed on Arm A

Exclusion Criteria:

* Patients must not have documented iron deficiency; all patients must have documented marrow iron stores; if marrow iron stain is not available, the transferrin saturation must be \> 20% or a serum ferritin \> 100 ng/mL
* Women must not be pregnant or breastfeeding; females of childbearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days and again within 24 hours prior to starting cycle 1 of lenalidomide; a female of childbearing potential (FCBP) is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months; FCBP must also agree to ongoing pregnancy testing)
* Patients must not have prior therapy with lenalidomide
* Patients must not have a diagnosis of uncontrolled seizure or uncontrolled hypertension
* Patients must not have proliferative (WBC \>= 12,000/mcL) chronic myelomonocytic leukemia (CMML); WBC must be \< 12,000/mcL
* Patients must not have MDS secondary to treatment with radiotherapy, chemotherapy, and/or immunotherapy for malignant or autoimmune diseases
* Prior thalidomide therapy is allowed, however, patients must not have prior \>= grade-3 allergic reactions to thalidomide
* Patients must not have prior history of desquamating rash from thalidomide at time of study entry
* Patients must not have clinically significant anemia resulting from iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis, or gastrointestinal bleeding
* Patients must not have used cytotoxic chemotherapeutic agents or experimental agents (agents that are not commercially available) for the treatment of MDS within 8 weeks of randomization
* Patients must not have prior history of malignancy other than MDS (except basal cell or squamous skin cell carcinoma or carcinoma in situ of the cervix or breast) unless the subject has been confirmed free of disease for \>= 3 years
* Patients must not have any serious medical condition or any other unstable medical co-morbidity, or psychiatric illness that will prevent the subject from signing the informed consent form or will place the subject at unacceptable risk if he/she participates in the study
* Patients must not have a history of thrombo-embolic events within 3 years prior to study randomization
* Patients must not have known human immunodeficiency virus (HIV)-1 seropositivity because HIV can be an alternate cause of anemia.
* Patients must not have a known allergic reaction to epoetin alfa (Procrit) or human serum albumin
* Exclusion criteria for crossover registration from Arm A (lenalidomide alone) to Arm B (lenalidomide and epoetin alfa):
* Patients must not have a limiting unresolved grade 3 or greater toxicity from lenalidomide monotherapy or drug intolerance preventing continuation of lenalidomide treatment
D: Inclusion Criteria:

* Subjects with non-myeloid malignancy
* At least 12 additional weeks of cyclic cytotoxic chemotherapy anticipated regardless of schedule
* Hemoglobin concentration less than 11.0 g/dL within 24 hours before randomization
* Adequate serum folate and vitamin B12
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
* Of legal age at the time written informed consent is obtained

Exclusion Criteria:

* Known history of seizure disorder
* Known primary hematologic disorder causing anemia other than non-myeloid malignancies
* Unstable/uncontrolled cardiac condition
* Clinically significant inflammatory disease
* Other diagnoses not related to the cancer which can cause anemia
* Inadequate renal and liver function
* Iron deficiency
* Known positive test for HIV infection
* Previously suspected of or confirmed to have neutralizing antibodies to rHuEPO
* Received more than 2 red blood cell (RBC) transfusions within 4 weeks of randomization; or any RBC transfusion within 14 days before randomization; or any planned RBC transfusion between randomization and study day 1
* Received any erythropoietic therapy within 4 weeks of study day 1 or any planned erythropoietic therapy between randomization and study day 1
* Other investigational procedures
* Currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug trial(s), or subject receiving other investigational agent(s)
* Pregnant or breast feeding
* Not using adequate contraceptive precautions
* Previously randomized into this study
* Known hypersensitivity to any products to be administered
* Concerns for subject's compliance

Answer: D