Lymphoblastic Leukemia, Acute, Childhood, Lymphoblastic Lymphoma, Peripheral T-cell Lymphoma
Conditions
Keywords
Relapse, Lymphoblastic, Leukemia, Refractory, Temsirolimus, Acute, Childhood, Pediatric, ALL, NHL, LL, PTL
Brief summary
This is a phase I study of temsirolimus (Torisel) combined with dexamethasone, cyclophosphamide and etoposide in patients with relapsed acute lymphoblastic leukemia (ALL), lymphoblastic lymphoma (LL) or peripheral T-cell lymphoma (PTL).
Detailed description
Studies have shown that mTOR inhibitors (MTI) inhibit growth of pre-B and T-cell ALL cell lines in vitro and in ALL xenograft models. The MTI temsirolimus was chosen for use in this study due to its weekly intravenous dosing, its more predictable blood levels, and availability of a single-agent pediatric MTD and its sustained biologic effect due to conversion to sirolimus. This study will determine the maximum tolerated dose of temsirolimus that can given in combination with dexamethasone, cyclophosphamide and etoposide in relapsed ALL, LL or PTL. A standard 3-patient cohort dose-escalation design will be used. Response to treatment will be evaluated. Biology tests will be done to evaluate minimal residual disease (MRD), temsirolimus' effect on glucocorticoid resistance, and mTOR inhibition.
Interventions
DRUGTemsirolimus
Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8.
DRUGEtoposide
100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5.
DRUGCyclophosphamide
440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.
DRUGMethotrexate
PATIENTS WITH CNS 1 COURSES 2, 4, 6, 8: Give intrathecally to patients who were CNS1 at study entry day 1 of each course at the doses listed below. * Age 1 - 1.99 give 8 mg of methotrexate * Age 2 - 2.99 give10 mg of methotrexate * Age 3 - 8.99 give 12 mg of methotrexate * Age ≥ 9 give 15 mg of methotrexate PATIENTS WITH CNS 2 or 3 DISEASE -COURSE 1: Give intrathecally to patients with CNS 2 or 3 disease at the doses defined by age below on day 6 and then weekly until the patient is CNS 1. COURSES 2-8: Give intrathecally to patients who were CNS 3 at study entry on day 1 of each course. * 8 mg for patients age 1-1.99 * 10 mg for patients age 2-2.99 * 12 mg for patients 3-8.99 years of age * 15 mg for patients \>9 years of age
DRUGHydrocortisone
Given with Methotrexate and Cytarabine for patients with CNS 2 or 3 disease. COURSE 1: Give intrathecally to patients with CNS 2 or 3 disease at the doses defined by age below on day 6 and then weekly until the patient is CNS 1. COURSES 2-8: Give intrathecally to patients who were CNS 3 at study entry on day 1 of each course. * 8 mg for patients age 1-1.99 * 10 mg for patients age 2-2.99 * 12 mg for patients 3-8.99 years of age * 15 mg for patients \>9 years of age
DRUGCytarabine
For Patients who are CNS1 COURSE 1: Give intrathecally to patients with CNS1 disease at the dose defined by age below on day 1 of course 1 if no other IT was given within 1 week of day 1 of course 1 * Age 1 - 1.99 give 30 mg of Cytarabine * Age 2 - 2.99 give 50mg of Cytarabine * Age ≥ 3 give 70 mg of Cytabine For Patients with CNS 2 or 3 Disease COURSE 1: Give intrathecally to patients with CNS 2 or 3 disease at the doses defined by age below on day 1 if no other IT chemotherapy given within 1 week of day 1 of course 1. Then give weekly until the patient is CNS 1 or 2 (investigator discretion). No more than 5 weekly doses to be given in cycle 1. COURSES 2-8: Give intrathecally to patients who were CNS 2or 3 at study entry on day 1 of each course. * 16 mg for patients age 1-1.99 * 20 mg for patients age 2-2.99 * 24 mg for patients 3-8.99 years of age * 30 mg for patients \>9 years of age
Sponsors
Pfizer
Therapeutic Advances in Childhood Leukemia Consortium
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This study follows a standard 3+3 patient cohort escalation design, as described below: 1. Three patients are entered at the first dose level 2. If 0/3 experiences DLT at a given dose level, then the dose is escalated to the next higher level, if a higher dose level exists, and three patients are enrolled. If a higher dose level does not exists, up to three more patients are accrued at the same dose level. 3. If 1/3 experiences DLT at current dose, then up to three more patients are accrued at the same dose level. 4. If 2 or more DLTs are observed in a three-patient or six-patient cohort at a given dose level, then the MTD has been exceeded, dose escalation will be stopped, and up to three additional patients will be enrolled at the next lower dose level, if a lower dose level exists (unless six patients have already been treated at that prior dose).
Eligibility
Sex/Gender
ALL
Age
1 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
-Patients must be greater than or equal to 12 months and ≤ 21 years of age at the time of study enrollment. Patients must have one of the following: Leukemia * Bone marrow involvement defined as ALL ≥ 25% blasts (M2 or M3) with or without extramedullary involvement. * Refractory bone marrow involvement defined as MRD ≥ 0.1% blasts done at a COG-approved MRD testing lab after most recent treatment regimen. in the bone marrow (M23) and any CNS status. OR * Newly diagnosed patients (T or B-cell ALL) with refractory bone marrow involvement after Consolidation therapy are eligible. * First relapse B-cell ALL patients are eligible with refractory disease. * Second or greater relapse B-cell patients are eligible at time of relapse or with refractory disease. * First or greater relapse T-cell ALL patients are eligible at time of relapse or with refractory disease. * Isolated CNS 2 or 3 patients with \< 0.1% MRD bone marrow involvement are not eligible. Lymphoma * Patient must have relapsed or refractory lymphoblastic lymphoma or peripheral T-cell lymphoma. * Patient must have histologic verification of disease at original diagnosis. * Patient must have evaluable or measurable disease documented by clinical or radiographic criteria or bone marrow disease present at study entry. * Patients may have CNS 2 or 3 disease Karnofsky greater than or equal to 50% for patients \> 16 years of age and Lansky greater than or equal to 50 for patients ≤ 16 years of age. Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy. Patients with leukemia or lymphoma who relapse while receiving maintenance chemotherapy will not be required to have a waiting period before enrollment onto this study. At least 14 days must have elapsed after the completion of cytotoxic therapy, with the exception of hydroxyurea. Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor. Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair Immunotherapy: At least 30 days after the completion of any type of immunotherapy, e.g. tumor vaccines. or chimeric antigen receptor T cell (CART) therapy or tumor vaccines. Monoclonal antibodies: At least 3 half-lives of the antibody must have elapsed after the last dose of a monoclonal antibody. (ie: Rituximab = 66 days, Epratuzumab = 69 days). Patients must have been off blinatumomab infusion for at least 4 days and all drug-related toxicity must have resolved to grade 2 or lower as outlined in the inclusion and
Exclusion criteria
XRT: At least 14 days after local palliative XRT (small port); At least 84 days must have elapsed if prior TBI, craniospinal XRT or if greater than or equal to 50% radiation of pelvis; At least 42 days must have elapsed if other substantial marrow radiation. Stem Cell Infusion: No evidence of active graft vs. host disease and at least 84 days must have elapsed after transplant or stem cell infusion. Adequate Bone Marrow Function Defined as: Blood counts are not required to be normal prior to enrollment on trial. However, platelet count must be greater than or equal to 20,000/mm3 to initiate therapy (may receive platelet transfusions). Patients should not be known to be refractory to red blood cell or platelet transfusions. Adequate Renal Function Defined as: * Creatinine clearance or radioisotope GFR greater than or equal to 70ml/min/1.73 m2 or * Normal serum creatinine based on age and gender. Adequate Liver Function Defined as: * Total bilirubin (sum of conjugated + unconjugated) must be less than or equal to 1.5 x normal per institutional normal values for age. * SGPT (ALT) and SGOT (AST) must be less than 3 x institutional upper limit of normal (Grade 1 or less per CTCAE 4). --GGT must be less than 2.5 x institutional upper limit of normal (Grade 1 or less per CTCAE 4). * Serum albumin greater than or equal to 2 g/dL. * The hepatic requirements may be waived for patients with elevations clearly due to leukemic infiltration after consultation with the Study Chair or Vice Chair. * Fasting or non-fasting serum triglyceride level ≤ 300 mg/dL and serum cholesterol level ≤ 300 mg/dL. Adequate Cardiac Function Defined As: * Shortening fraction of ≥ 27% by echocardiogram, or * Ejection fraction of ≥ 50% by gated radionuclide study. Adequate Pulmonary Function Defined as: * Pulse oximetry \> 94% on room air (\> 90% if at high altitude) * No evidence of dyspnea at rest and no exercise intolerance. * Baseline chest x-ray with no evidence of active infectious disease or pneumonitis. Reproductive Function * Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed prior to enrollment. * Female patients with infants must agree not to breastfeed their infants while on this study. * Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study. * Random or fasting glucose within the upper limits of normal for age. If the initial blood glucose is non-fasting and above normal limits a fasting glucose can be obtained and must be within the upper limits of normal for age.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients That Experienced DLT During Cycle 1 of Therapy | Cycle 1 (a minimum of 4 weeks and a max of 8 weeks) | The incidence of dose limiting toxicity (DLT) will be measured. The maximum tolerated dose will be the highest study dose at which 1 or fewer of six patients experience DLT during cycle 1 of therapy. All these analyses will be descriptive and exploratory and hypotheses generating in nature. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate at the Completion of 1 Cycle of Study Treatment | Cycle 1 (a minimum of 4 weeks and a max of 8 weeks) | CR = Complete remission defined as attainment of bone marrow with \<5% blasts with no evidence of circulating blasts or extramedullary disease and with recovery of peripheral counts (absolute neutrophil counts (ANC) \> or = to 500/uL and platelet count \> or = to 50,000 microliters) CRi = Complete remission with incomplete blood count recovery defined as attainment of bone marrow with \>5% blasts with no evidence of circulating blasts or extramedullary disease but insufficient recovery of ANC \< 500/uL or platelets \< 50,000 microliters PR = partial remission defined as complete disappearance of circulating blasts and achievement of 5-25% blasts if greater than 25% blasts originally without new sites of extramedullary disease and with recovery of ANC. SD = stable disease defined as not satisfying criteria for PD, or has recovery of ANC \> or = to 500/uL and fails to qualify for CR, CRi, or PR PD = progressive disease defined as an increase of at least 25% in bone marrow leukemic cells |
| Minimum Residual Disease (MRD) Levels Present at End of Cycle 1 Therapy in Patients | Cycle 1 (a minimum of 4 weeks and a max of 8 weeks) | MRD positive is defined as \> or = to 0.1% MRD MRD negative is define as \< 0.1% MRD All these analyses will be descriptive and exploratory and hypotheses generating in nature. |
Countries
Australia, Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose Level 1 This is the starting dose of temsirolimus at 7.5 mg/m\^2 given IV. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8.
Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8.
Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5.
Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes. | 3 |
| Dose Level 2 If Dose Level 1 is tolerated, the study will escalate to Dose Level 2 following the dose escalation schedule. Dose Level 2 will be administered via IV at 10 mg/m\^2. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8.
Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8.
Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5.
Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes. | 4 |
| Dose Level 3 If Dose Level 2 is tolerated, the study will escalate to Dose Level 3 following the dose escalation schedule. Dose Level 3 will be administered via IV at 15 mg/m\^2. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8.
Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8.
Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5.
Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes. | 6 |
| Dose Level 4 If Dose Level 3 is tolerated, the study will escalate to Dose Level 4 following the dose escalation schedule. Dose Level 4 will be administered via IV at 25 mg/m\^2. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8. Temsirolimus will not be escalated beyond Dose Level 4.
Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8.
Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5.
Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes. | 3 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Dose Level 1 | Total | Dose Level 4 | Dose Level 3 | Dose Level 2 |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 3 Participants | 16 Participants | 3 Participants | 6 Participants | 4 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 8 Participants | 1 Participants | 6 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 7 Participants | 2 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Prior Therapy Regimens # of prior therapies : 1 prior therapy | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Prior Therapy Regimens # of prior therapies : 2 prior therapies | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants |
| Prior Therapy Regimens # of prior therapies : 3 prior therapies | 2 Participants | 5 Participants | 0 Participants | 2 Participants | 1 Participants |
| Prior Therapy Regimens # of prior therapies : 4 prior therapies | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Prior Therapy Regimens # of prior therapies : 5 prior therapies | 0 Participants | 4 Participants | 2 Participants | 1 Participants | 1 Participants |
| Prior Therapy Regimens # of prior therapies : 6 prior therapies | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Prior Therapy Regimens # of prior therapies : 7 prior therapies | 1 Participants | 3 Participants | 0 Participants | 2 Participants | 0 Participants |
| Prior Therapy Regimens Prior CAR-T cell therapy : No | 2 Participants | 11 Participants | 2 Participants | 4 Participants | 3 Participants |
| Prior Therapy Regimens Prior CAR-T cell therapy : Yes | 1 Participants | 4 Participants | 1 Participants | 2 Participants | 0 Participants |
| Prior Therapy Regimens Prior transplant : No | 1 Participants | 7 Participants | 3 Participants | 2 Participants | 1 Participants |
| Prior Therapy Regimens Prior transplant : Yes | 2 Participants | 8 Participants | 0 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 4 Participants | 1 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 10 Participants | 1 Participants | 3 Participants | 3 Participants |
| Region of Enrollment Australia | 0 participants | 1 participants | 1 participants | 0 participants | 0 participants |
| Region of Enrollment Canada | 1 participants | 2 participants | 0 participants | 0 participants | 1 participants |
| Region of Enrollment United States | 2 participants | 13 participants | 2 participants | 6 participants | 3 participants |
| Sex: Female, Male Female | 0 Participants | 6 Participants | 2 Participants | 4 Participants | 0 Participants |
| Sex: Female, Male Male | 3 Participants | 10 Participants | 1 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 3 | 1 / 3 | 3 / 6 | 2 / 3 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 6 / 6 | 3 / 3 |
| serious Total, serious adverse events | 3 / 3 | 0 / 3 | 3 / 6 | 0 / 3 |
Outcome results
Primary
Number of Patients That Experienced DLT During Cycle 1 of Therapy
The incidence of dose limiting toxicity (DLT) will be measured. The maximum tolerated dose will be the highest study dose at which 1 or fewer of six patients experience DLT during cycle 1 of therapy. All these analyses will be descriptive and exploratory and hypotheses generating in nature.
Time frame: Cycle 1 (a minimum of 4 weeks and a max of 8 weeks)
Population: Number of patients that initiated and completed study treatment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Level 1 | Number of Patients That Experienced DLT During Cycle 1 of Therapy | Number of patients that did not experience DLT | 3 Participants |
| Dose Level 1 | Number of Patients That Experienced DLT During Cycle 1 of Therapy | Number of patient that did experience DLT | 0 Participants |
| Dose Level 2 | Number of Patients That Experienced DLT During Cycle 1 of Therapy | Number of patient that did experience DLT | 0 Participants |
| Dose Level 2 | Number of Patients That Experienced DLT During Cycle 1 of Therapy | Number of patients that did not experience DLT | 3 Participants |
| Dose Level 3 | Number of Patients That Experienced DLT During Cycle 1 of Therapy | Number of patients that did not experience DLT | 5 Participants |
| Dose Level 3 | Number of Patients That Experienced DLT During Cycle 1 of Therapy | Number of patient that did experience DLT | 1 Participants |
| Dose Level 4 | Number of Patients That Experienced DLT During Cycle 1 of Therapy | Number of patients that did not experience DLT | 3 Participants |
| Dose Level 4 | Number of Patients That Experienced DLT During Cycle 1 of Therapy | Number of patient that did experience DLT | 0 Participants |
Secondary
Minimum Residual Disease (MRD) Levels Present at End of Cycle 1 Therapy in Patients
MRD positive is defined as \> or = to 0.1% MRD MRD negative is define as \< 0.1% MRD All these analyses will be descriptive and exploratory and hypotheses generating in nature.
Time frame: Cycle 1 (a minimum of 4 weeks and a max of 8 weeks)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Level 1 | Minimum Residual Disease (MRD) Levels Present at End of Cycle 1 Therapy in Patients | MRD positive | 3 Participants |
| Dose Level 1 | Minimum Residual Disease (MRD) Levels Present at End of Cycle 1 Therapy in Patients | MRD negative | 0 Participants |
| Dose Level 2 | Minimum Residual Disease (MRD) Levels Present at End of Cycle 1 Therapy in Patients | MRD negative | 1 Participants |
| Dose Level 2 | Minimum Residual Disease (MRD) Levels Present at End of Cycle 1 Therapy in Patients | MRD positive | 2 Participants |
| Dose Level 3 | Minimum Residual Disease (MRD) Levels Present at End of Cycle 1 Therapy in Patients | MRD positive | 5 Participants |
| Dose Level 3 | Minimum Residual Disease (MRD) Levels Present at End of Cycle 1 Therapy in Patients | MRD negative | 1 Participants |
| Dose Level 4 | Minimum Residual Disease (MRD) Levels Present at End of Cycle 1 Therapy in Patients | MRD positive | 2 Participants |
| Dose Level 4 | Minimum Residual Disease (MRD) Levels Present at End of Cycle 1 Therapy in Patients | MRD negative | 1 Participants |
Secondary
Response Rate at the Completion of 1 Cycle of Study Treatment
CR = Complete remission defined as attainment of bone marrow with \<5% blasts with no evidence of circulating blasts or extramedullary disease and with recovery of peripheral counts (absolute neutrophil counts (ANC) \> or = to 500/uL and platelet count \> or = to 50,000 microliters) CRi = Complete remission with incomplete blood count recovery defined as attainment of bone marrow with \>5% blasts with no evidence of circulating blasts or extramedullary disease but insufficient recovery of ANC \< 500/uL or platelets \< 50,000 microliters PR = partial remission defined as complete disappearance of circulating blasts and achievement of 5-25% blasts if greater than 25% blasts originally without new sites of extramedullary disease and with recovery of ANC. SD = stable disease defined as not satisfying criteria for PD, or has recovery of ANC \> or = to 500/uL and fails to qualify for CR, CRi, or PR PD = progressive disease defined as an increase of at least 25% in bone marrow leukemic cells
Time frame: Cycle 1 (a minimum of 4 weeks and a max of 8 weeks)
Population: All these analyses will be descriptive and exploratory and hypotheses generating in nature.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Level 1 | Response Rate at the Completion of 1 Cycle of Study Treatment | PR | 1 Participants |
| Dose Level 1 | Response Rate at the Completion of 1 Cycle of Study Treatment | PD | 1 Participants |
| Dose Level 1 | Response Rate at the Completion of 1 Cycle of Study Treatment | SD | 0 Participants |
| Dose Level 1 | Response Rate at the Completion of 1 Cycle of Study Treatment | CRi | 1 Participants |
| Dose Level 1 | Response Rate at the Completion of 1 Cycle of Study Treatment | CR | 0 Participants |
| Dose Level 2 | Response Rate at the Completion of 1 Cycle of Study Treatment | CR | 1 Participants |
| Dose Level 2 | Response Rate at the Completion of 1 Cycle of Study Treatment | CRi | 0 Participants |
| Dose Level 2 | Response Rate at the Completion of 1 Cycle of Study Treatment | PR | 1 Participants |
| Dose Level 2 | Response Rate at the Completion of 1 Cycle of Study Treatment | SD | 1 Participants |
| Dose Level 2 | Response Rate at the Completion of 1 Cycle of Study Treatment | PD | 0 Participants |
| Dose Level 3 | Response Rate at the Completion of 1 Cycle of Study Treatment | CR | 1 Participants |
| Dose Level 3 | Response Rate at the Completion of 1 Cycle of Study Treatment | CRi | 0 Participants |
| Dose Level 3 | Response Rate at the Completion of 1 Cycle of Study Treatment | SD | 1 Participants |
| Dose Level 3 | Response Rate at the Completion of 1 Cycle of Study Treatment | PR | 1 Participants |
| Dose Level 3 | Response Rate at the Completion of 1 Cycle of Study Treatment | PD | 3 Participants |
| Dose Level 4 | Response Rate at the Completion of 1 Cycle of Study Treatment | PR | 0 Participants |
| Dose Level 4 | Response Rate at the Completion of 1 Cycle of Study Treatment | CR | 0 Participants |
| Dose Level 4 | Response Rate at the Completion of 1 Cycle of Study Treatment | CRi | 1 Participants |
| Dose Level 4 | Response Rate at the Completion of 1 Cycle of Study Treatment | PD | 1 Participants |
| Dose Level 4 | Response Rate at the Completion of 1 Cycle of Study Treatment | SD | 1 Participants |