Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia, Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2), Adult Acute Myeloblastic Leukemia Without Maturation (M1), Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Adult Acute Myelomonocytic Leukemia (M4), Adult Erythroleukemia (M6a), Adult Pure Erythroid Leukemia (M6b), Secondary Acute Myeloid Leukemia, Untreated Adult Acute Myeloid Leukemia
Conditions
Brief summary
This phase II trial is studying how well lenalidomide works in treating older patients with acute myeloid leukemia with abnormal chromosome 5q. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing.
Detailed description
PRIMARY OBJECTIVES: I. Test whether the complete response rate among older patients with previously untreated acute myeloid leukemia (AML) with the del (5q) cytogenetic abnormality treated with lenalidomide is sufficiently high to warrant a phase III investigation. II. Estimate the frequency and severity of toxicities of this drug in these patients. III. Correlate, in a preliminary manner, additional cytogenetic abnormalities with response to lenalidomide. IV. Estimate the total (complete and partial) response rate and the cytogenetic response rate in these patients. OUTLINE: INDUCTION THERAPY: Patients receive oral lenalidomide once daily on days 1-14, 1-21, or 1-28 (course 1). Patients undergo bone marrow biopsy on day 28 or 35 to assess treatment efficacy. Patients with stable or improving disease (i.e., a decrease in blast percentage) without progressive disease proceed to maintenance therapy. MAINTENANCE THERAPY: Beginning within 42 days after completion of induction therapy, patients receive oral lenalidomide once daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for up to 5 years.
Interventions
Given orally
Sponsors
Study design
Eligibility
Inclusion criteria
* Morphologically confirmed diagnosis of acute myeloid leukemia (AML) by bone marrow aspiration and biopsy within the past 14 days * Diagnostic biopsy within the past 28 days with marrow blast percentage ≥ 70% allowed provided no potentially antileukemic therapy was received after biopsy * Cytogenetic evidence of del (5q) abnormality by conventional karyotyping or fluorescence in situ hybridization (FISH) * Previously untreated disease * Must have declined standard AML cytotoxic chemotherapy regimens * WBC ≤ 30,000/mm³ * History of prior myelodysplastic syndromes (MDS) allowed * No acute promyelocytic leukemia (FAB M3) * No blastic transformation of chronic myelogenous leukemia * Zubrod performance status 0-2 * Bilirubin ≤ 2.5 times upper limit of normal (ULN) (unless elevation is due primarily to elevated unconjugated hyperbilirubinemia secondary to Gilbert's syndrome or hemolysis, but not to liver dysfunction) * AST and ALT ≤ 3.5 times ULN * Creatinine ≤ 1.5 times ULN * HIV negative * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use 2 forms of effective contraception at least 4 weeks prior to, during, and for 4 weeks after completion of study treatment * No known allergy to thalidomide * Concurrent enrollment on SWOG-S9910 allowed (for SWOG patients) * No prior systemic chemotherapy for acute leukemia except hydroxyurea * Single-dose intrathecal chemotherapy allowed before or concurrently with induction chemotherapy * No prior AML induction-type chemotherapy or high-dose chemotherapy with hematopoietic stem cell support * Prior hematopoietic growth factors, thalidomide, arsenic trioxide, signal-transduction inhibitors, azacitidine, and low-dose cytarabine (i.e., \< 100 mg/m²/day) for treatment of MDS allowed * At least 30 days since prior therapy for MDS (excluding growth factors) * No prior lenalidomide for MDS * At least 6 months since prior chemotherapy or radiotherapy for another malignancy * No concurrent therapy for another malignancy * Concurrent hormonal therapy allowed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response | Up to 5 years | Morphologic complete remission (CR): ANC \>=1,000/mcl, platelet count \>=100,000/mcl, \<5% bone marrow blasts, no Auer rods, no evidence of extramedullary disease. Morphologic complete remission with incomplete blood count recovery (CRi): Same as CR but ANC may be \<1,000/mcl and/or platelet count \<100,000/mcl. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Up to 5 years | Only adverse events that are possibly, probably or definitely related to study drug are reported. |
| Cytogenetic Abnormalities | Up to 5 years | Number of baseline cytogenetic abnormalities by responders (CR, CRi, and PR) and nonresponders. |
| Total Response | Up to 5 years | Morphologic complete remission (CR): ANC \>=1,000/mcl, platelet count \>=100,000/mcl, \<5% bone marrow blasts, no Auer rods, no evidence of extramedullary disease. Morphologic complete remission with incomplete blood count recovery (CRi): Same as CR but ANC may be \<1,000/mcl and/or platelet count \<100,000/mcl. Partial remission (PR): ANC \>1,000/mcl, platelet count \>100,000/mcl, and at least 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts \<5% with persistent Auer rods. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Induction Therapy Oral lenalidomide once daily on days 1-14, 1-21, or 1-28 | 37 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Induction Therapy | Adverse Event | 7 |
| Induction Therapy | Death | 7 |
| Induction Therapy | Death before starting protocol therapy | 1 |
| Induction Therapy | Not eligible | 3 |
| Induction Therapy | Not protocol specified | 1 |
| Induction Therapy | Progression/Relapse | 8 |
| Maintenance Therapy | Death | 2 |
| Maintenance Therapy | Not eligible | 4 |
| Maintenance Therapy | Not protocol specified | 3 |
| Maintenance Therapy | Progression/Relapse | 3 |
Baseline characteristics
| Characteristic | Induction Therapy |
|---|---|
| Age, Continuous | 73.7 years |
| Disease Onset De Novo | 16 participants |
| Disease Onset MDS related | 19 participants |
| Disease Onset Treatment related | 2 participants |
| Hispanic No | 32 participants |
| Hispanic Unknown | 4 participants |
| Hispanic Yes | 1 participants |
| Performance Status 0 | 7 participants |
| Performance Status 1 | 30 participants |
| Race/Ethnicity, Customized Black or African American | 3 participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 1 participants |
| Race/Ethnicity, Customized White | 33 participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 34 / 37 | 8 / 8 |
| serious Total, serious adverse events | 24 / 37 | 4 / 8 |
Outcome results
Complete Response
Morphologic complete remission (CR): ANC \>=1,000/mcl, platelet count \>=100,000/mcl, \<5% bone marrow blasts, no Auer rods, no evidence of extramedullary disease. Morphologic complete remission with incomplete blood count recovery (CRi): Same as CR but ANC may be \<1,000/mcl and/or platelet count \<100,000/mcl.
Time frame: Up to 5 years
Population: Eligible patients who began protocol therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Therapy | Complete Response | 11 percentage of participants |
Cytogenetic Abnormalities
Number of baseline cytogenetic abnormalities by responders (CR, CRi, and PR) and nonresponders.
Time frame: Up to 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Induction Therapy | Cytogenetic Abnormalities | 8 Number of abnormalities |
| Maintenance Therapy | Cytogenetic Abnormalities | 8 Number of abnormalities |
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug
Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time frame: Up to 5 years
Population: Eligible patients who received any treatment and were assessed for toxicity were included in the adverse event summaries. Any CTCAE 3.0 event of Grade 3 (severe), Grade 4 (life threatening) or Grade 5 (fatal) which were deemed to be related to protocol treatment are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Inf (clin/microbio) w/Gr 3-4 neuts - Lung | 5 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Diarrhea | 2 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Inf (clin/microbio) w/Gr 3-4 neuts - Oral cav-gums | 1 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Anorexia | 1 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Inf (clin/microbio) w/Gr 3-4 neuts - Skin | 1 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Dyspnea (shortness of breath) | 2 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Inf w/normal ANC or Gr 1-2 neutrophils - Blood | 0 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Cardiac-ischemia/infarction | 1 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Leukocytes (total WBC) | 14 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Fatigue (asthenia, lethargy, malaise) | 11 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Lymphopenia | 2 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Adult respiratory distress syndrome (ARDS) | 1 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Muscle weakness, not d/t neuropathy - body/general | 3 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Febrile neutropenia | 15 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Nausea | 1 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Cough | 1 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Neuropathy: motor | 1 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Glucose, serum-high (hyperglycemia) | 2 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Neutrophils/granulocytes (ANC/AGC) | 16 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Bilirubin (hyperbilirubinemia) | 1 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Platelets | 21 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Hemoglobin | 7 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Pneumonitis/pulmonary infiltrates | 4 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Creatinine | 3 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Potassium, serum-low (hypokalemia) | 3 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Induration/fibrosis (skin and subcutaneous tissue) | 0 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Pulmonary/Upper Respiratory-Other (Specify) | 2 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | AST, SGOT | 1 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Rash/desquamation | 2 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Inf (clin/microbio) w/Gr 3-4 neuts - Esophagus | 1 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Renal failure | 1 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Dermatology/Skin-Other (Specify) | 1 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Sodium, serum-high (hypernatremia) | 1 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Inf (clin/microbio) w/Gr 3-4 neuts - Lip/perioral | 1 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Sodium, serum-low (hyponatremia) | 1 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Calcium, serum-low (hypocalcemia) | 3 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Vomiting | 1 Participants |
| Induction Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | ALT, SGPT (serum glutamic pyruvic transaminase) | 1 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Vomiting | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | ALT, SGPT (serum glutamic pyruvic transaminase) | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | AST, SGOT | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Adult respiratory distress syndrome (ARDS) | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Anorexia | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Bilirubin (hyperbilirubinemia) | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Calcium, serum-low (hypocalcemia) | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Cardiac-ischemia/infarction | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Cough | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Creatinine | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Dermatology/Skin-Other (Specify) | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Diarrhea | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Dyspnea (shortness of breath) | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Fatigue (asthenia, lethargy, malaise) | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Febrile neutropenia | 2 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Glucose, serum-high (hyperglycemia) | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Hemoglobin | 2 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Induration/fibrosis (skin and subcutaneous tissue) | 1 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Inf (clin/microbio) w/Gr 3-4 neuts - Esophagus | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Inf (clin/microbio) w/Gr 3-4 neuts - Lip/perioral | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Inf (clin/microbio) w/Gr 3-4 neuts - Lung | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Inf (clin/microbio) w/Gr 3-4 neuts - Oral cav-gums | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Inf (clin/microbio) w/Gr 3-4 neuts - Skin | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Inf w/normal ANC or Gr 1-2 neutrophils - Blood | 1 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Leukocytes (total WBC) | 4 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Lymphopenia | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Muscle weakness, not d/t neuropathy - body/general | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Nausea | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Neuropathy: motor | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Neutrophils/granulocytes (ANC/AGC) | 5 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Platelets | 3 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Pneumonitis/pulmonary infiltrates | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Potassium, serum-low (hypokalemia) | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Pulmonary/Upper Respiratory-Other (Specify) | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Rash/desquamation | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Renal failure | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Sodium, serum-high (hypernatremia) | 0 Participants |
| Maintenance Therapy | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Sodium, serum-low (hyponatremia) | 1 Participants |
Total Response
Morphologic complete remission (CR): ANC \>=1,000/mcl, platelet count \>=100,000/mcl, \<5% bone marrow blasts, no Auer rods, no evidence of extramedullary disease. Morphologic complete remission with incomplete blood count recovery (CRi): Same as CR but ANC may be \<1,000/mcl and/or platelet count \<100,000/mcl. Partial remission (PR): ANC \>1,000/mcl, platelet count \>100,000/mcl, and at least 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts \<5% with persistent Auer rods.
Time frame: Up to 5 years
Population: Eligible patients who began protocol therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction Therapy | Total Response | 14 percentage of participants |