Acute Leukemia, Leukemia, Lymphocytic, Lymphoblastic Lymphoma, Recurrent Disease, T-cell Leukemia, T-cell Lymphoma
Conditions
Brief summary
AINV18P1 is a Phase 1 study where palbociclib will be administrated in combination with a standard re-induction platform in pediatric relapsed Acute Lymphoblastic Leukemia (ALL) and lymphoblastic lymphoma (LL). LL patients are included because the patient population is rare and these patients are most commonly treated with ALL regimens. The proposed palbociclib starting dose for this study will be 50 mg/m\^2/day for 21 days.
Detailed description
PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of palbociclib administered in combination with re-induction chemotherapy in pediatric patients with relapsed B- or T-lineage ALL/LL. II. To define and describe the toxicities of palbociclib administered on this schedule. III. To characterize the pharmacokinetics of palbociclib in pediatric patients with relapsed B- or T-lineage ALL/LL. SECONDARY OBJECTIVES: I. To preliminarily define the antitumor activity of palbociclib in combination with chemotherapy for children with relapsed ALL/LL within the confines of a Phase 1 study. II. To assess the biologic activity of palbociclib in this patient population. OUTLINE: Patients receive Palbociclib PO (or via NG-tube) once daily on Days 1-21; Intrathecal cytarabine (IT ARAC) on Day 1, Doxorubicin IV push or infusion over 1-15 min on Day 4; Prednisone or prednisolone PO on days 4-31; Vincristine IV push or mini-bag per institutional policy on Days 4, 11, 18, and 25; and Pegaspargase IV over 1-2 hours on Days 5, and 18. If CNS3 leukemia is present, patients receive Intrathecal Triple Therapy (ITT) on days 4, 11,18, and 25. If CNS1 or 2 disease status, patients receive Methotrexate (IT MTX) on Days 18 and 32. Patients known to be CNS3 at study entry may receive ITT on Day 1 rather than IT ARAC. Treatment will be given for one cycle, 32 days, in the absence of disease progression or unacceptable toxicity.
Interventions
DRUGPalbociclib
Given PO (or via NG- tube)
DRUGCytarabine
Given intrathecally (IT)
DRUGMethotrexate
Given intrathecally (IT)
DRUGHydrocortisone
Given IT
DRUGDoxorubicin
Given intravenously (IV)
DRUGPrednisolone
Either prednisone or prednisolone is given PO
DRUGVincristine
Given IV
DRUGPegaspargase
Given IV
DRUGPrednisone
Either prednisone or prednisolone is given PO
Sponsors
Children's Oncology Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Months to 31 Years
Healthy volunteers
No
Inclusion criteria
* Patients with recurrent or refractory B- or T-lineage lymphoblastic leukemia and lymphoma. * Patients with leukemia must have ≥ 5% (M2 or M3) bone marrow blasts with or without an extramedullary site of relapse. Morphologic relapse for M2 should be confirmed using flow cytometry, FISH and/or cytogenetics or molecular techniques. * Patients with LL must have either measurable or evaluable disease. * Patients with first or greater relapsed T-lineage ALL or LL and second or greater relapsed B-lineage ALL or LL are eligible. * Patients with primary refractory disease with at least 2 prior induction attempts or first relapse refractory to at least one prior re-induction attempt are eligible. * Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50 for patients \<= 16 years of age. * Note: Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. * Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately. 1. Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive. See DVL homepage for commercial and Phase 1 investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment. * A waiting period prior to enrollment is not required for patients receiving standard cytotoxic maintenance chemotherapy (i.e., corticosteroid, vincristine, 6MP, and/or methotrexate). * Intrathecal cytotoxic therapy: No waiting period is required for patients having received intrathecal cytarabine, methotrexate, and/or hydrocortisone. Intrathecal chemotherapy given at the time of diagnostic LP to evaluate for relapse prior to study enrollment is allowed. * At least 14 days must have elapsed after the completion of other cytotoxic therapy, with the exception of hydroxyurea, for patients not receiving standard maintenance therapy. Additionally, patients must have fully recovered from all acute toxic effects of prior therapy. * NOTE: Cytoreduction with hydroxyurea in patients can be initiated and continued for up to 24 hours prior to the start of protocol therapy. * Note: Intrathecal chemotherapy that is given up to 72 hours prior to initiation of systemic chemotherapy per AINV18P1 counts as protocol therapy and not prior anti-cancer therapy. Intrathecal chemotherapy given \> 72 hours prior does not count as protocol therapy. 2. Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or ANC counts): \>= 7 days after the last dose of agent. See DVL homepage for commercial and Phase 1 investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment. * NOTE: Cytoreduction with prednisone or methylprednisolone for \<= 120 hours (5 days) in patients can be initiated and continued for up to 24 hours prior to the start of protocol therapy. 3. Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody with the exception of blinatumomab, and toxicity related to prior antibody therapy must be recovered to Grade \<= 1. Patients must have been off blinatumomab infusion for at least 14 days and all drug related toxicity must have resolved to Grade \<= 1. 4. Corticosteroids: If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid and toxicity related to prior immune therapy must be recovered to Grade \<= 1 off corticosteroids. 5. Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor. 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 and the study-assigned Research Coordinator. 6. Interleukins, Interferons and Cytokines (other than Hematopoietic Growth Factors): \>= 21 days after the completion of interleukins, interferon or cytokines (other than Hematopoietic Growth Factors) 7. Stem cell Infusions (with or without TBI): * Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including DLI or boost infusion: \>= 84 days after infusion and no evidence of GVHD. * Autologous stem cell infusion including boost infusion: \>= 42 days. 8. Cellular Therapy: \>= 30 days after the completion of any type of cellular therapy (e.g. modified T cells, NK cells, dendritic cells, etc.) 9. XRT/External Beam Irradiation including Protons: \>= 14 days after local XRT; \>= 150 days after TBI, craniospinal XRT or if radiation to \>= 50% of the pelvis; \>= 42 days if other substantial BM radiation. 10. Patients must not have received prior exposure to palbociclib or another CDK4/6 inhibitor. * Adequate Renal Function Defined as: * Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 or * A serum creatinine based on age/gender as follows: * Age: 1 to \< 2 years; Male: 0.6 mg/dL; Female: 0.6 mg/dL * Age: 2 to \< 6 years; Male: 0.8 mg/dL; Female: 0.8 mg/dL * Age: 6 to \< 10 years; Male: 1 mg/dL; Female: 1 mg/dL * Age: 10 to \< 13 years; Male: 1.2 mg/dL; Female: 1.2 mg/dL * Age: 13 to \< 16 years; Male: 1.5 mg/dL; Female: 1.4 mg/dL * Age: \>= 16 years; Male: 1.7 mg/dL; Female: 1.4 mg/dL * Adequate Liver Function Defined as: * bilirubin (sum of conjugated + unconjugated) \<= 1.5 x upper limit of normal (ULN) for age * SGPT (ALT) \<= 225 U/L unless disease-related. For the purpose of this study, the ULN for SGPT is 45 U/L. * Serum albumin \>= 2 g/dL. * Adequate Cardiac Function Defined As: * Shortening fraction of \>= 27% by echocardiogram, or * Ejection fraction of \>= 50% by gated radionuclide study. * All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
Exclusion criteria
* Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies. Based on the mechanism of action, palbociclib may be expected to cause fetal harm if used during pregnancy. Pregnancy tests must be obtained in girls who are post-menarche. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study therapy. Women of reproductive potential should use effective contraception during treatment and for at least 3 weeks after the last dose of palbociclib. Males with female partners of reproductive potential should use effective contraception during treatment and for 3 months after the last dose of palbociclib. Animal data suggests that palbociclib may affect male fertility. * Prednisone or methylprednisolone for ≤ 120 hours (5 days) may be administered for cytoreduction up to 24 hours prior to the start of protocol therapy and as treatment for allergic reactions or for physiologic replacement/stress dosing of hydrocortisone for documented adrenal insufficiency. Corticosteroids are not allowed for other indications. If used to modify immune adverse events related to prior therapy, ≥ 14 days must have elapsed since last dose of corticosteroid. * Patients who are currently receiving another investigational drug. * Patients who are currently receiving other anti-cancer agents are not eligible \[except patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy\]. * Patients who are currently receiving drugs that are strong inhibitors and/or inducers of CYP3A4 or sensitive CYP3A4 substrates and CYP3A4 substrates with a narrow therapeutic range are not eligible. Strong inducers or inhibitors of CYP3A4 are prohibited from 14 days prior to enrollment to the end of the study. * Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant. * Patients must be able to swallow intact capsules or liquid. Patients that are unable to swallow oral medications may receive palbociclib through an NG tube. G tube administration is not allowed. * Patients who have an uncontrolled infection defined as below: * Fever above 38.2°C within 48 hours of study enrollment with clinical signs of infection. Fever that is determined to be due to tumor burden is allowed if patients have documented negative blood cultures for at least 48 hours prior to enrollment and no concurrent signs or symptoms of active infection or hemodynamic instability. * A positive fungal culture within 30 days of study enrollment or active therapy for presumed invasive fungal infection. * Patients may be receiving IV or oral antibiotics to complete a course of therapy for a prior documented infection as long as cultures have been negative for at least 48 hours and signs or symptoms of active infection have resolved. For patients with c. difficile diarrhea, at least 72 hours of antibacterial therapy must have elapsed and stools must have normalized to baseline. * Active viral or protozoal infection requiring IV treatment. * Patients known to have one of the following concomitant genetic syndromes: Down syndrome, Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachmann syndrome or any other known bone marrow failure syndrome. * Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study. * Cumulative prior anthracycline exposure must not exceed 400 mg/m2 of DOXOrubicin equivalents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Dose Limiting Toxicities of Palbociclib | Up to 32 days | The frequency (%) of patients experiencing a cycle 1 dose limiting toxicity at least possibly attributable to Palbociclib by study part and dose level. |
| Frequency of Adverse Events of Palbociclib | Up to 26 months | The frequency (%) of patients experiencing adverse events at least possibly attributable to Palbociclib by study part and dose level. |
| Area Under the Drug Concentration Curve of Palbociclib | Up to 11 days | The median (min, max) of the area under the drug concentration curve for Palbociclib determined by measures at 0, 1, 2, 4, 8, and 24 hours post-dose on day 11 by study part and dose level. |
| Half-life of Palbociclib | Up to 11 days | The median (min, max) of the half-life of Palbociclib determined by measures at 0, 1, 2, 4, 8, and 24 hours post-dose on day 11 by study part and dose level. |
| Maximum Serum Concentration of Palbociclib | Up to 11 days | Median (min, max) of the maximum serum concentration of Palbociclib determined by measures at 0, 1, 2, 4, 8, and 24 hours post-dose on day 11 by study part and dose level |
| Time to Reach Maximum Serum Concentration of Palbociclib | Up to 11 days | Median (min, max) of the maximum time to reach serum concentration of Palbociclib determined by measures at 0, 1, 2, 4, 8, and 24 hours post-dose on day 11 by study part and dose level |
| Clearance of Palbociclib | Up to 11 days | Median (min, max) of the clearance of Palbociclib determined by measures at 0, 1, 2, 4, 8, and 24 hours post-dose on day 11 by study part and dose level |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CDK6 Expression of Palbociclib | Up to 4 days | Median (min,max) of CDK6 expression of palbociclib by study part and dose level |
| p27Kip1 Expression of Palbociclib | Up to 4 days | Median (min,max) of p27Kip1 expression of palbociclib by study part and dose level |
| Number of Participants With at Least Partial Response to Palbociclib | up to 26 months | Frequency (%) of patients with at least partial response to Palbociclib per leukemia/lymphoma specific response criteria: Complete Response (CR), M1 marrow (\<5% blasts) and absolute neutrophil count (ANC) at least 500/uL and platelet count at least 50000/uL without transfusion for 7 days; Complete response with incomplete recovery (CRi), M1 marrow (\<5% blasts), ANC\<500uL, platelet count \<50,000uL; Partial Response (PR), Complete disappearance of circulating blasts and achievement of M2 marrow status if M3 originally, without new sites of extramedullary disease, and with ANC ≥ 500/µL. Complete response in the marrow without resolution of extramedullary sites. Overall Response (OR) = CR+CRi+PR |
| DAPI Biological Activity of Palbociclib | up to 26 months | Median (min,max) of DAPI biological activity of palbociclib by study part and dose level |
| Ki67 Biological Activity of Palbociclib | Up to 32 days | Median (min,max) of CD1a biological activity of palbociclib |
| Absolute Peripheral Blast Count of Palbociclib | Up to 3 days | Median (min, max) of absolute peripheral blast count of palbociclib by study part and dose level |
| Radiographic Response of Palbociclib in Patients With LL Patients | Day 32 | Number of LL patients with radiographic response by study part and dose level. Complete Response (CR): Disappearance of all disease; Partial Response (PR): 50% decrease in SPD (the sum of the products of the largest diameter and the perpendicular diameter for a tumor mass). Total responders = CR+PR |
| RB1 Expression of Palbociclib | Up to 4 days | Median (min,max) of RB1 expression of palbociclib by study part and dose level |
| Phospho-RB1 Expression of Palbociclib | Up to 4 days | Median (min,max) of Phospho-RB1 expression of palbociclib by study part and dose level |
| Cyclin D3 Expression of Palbociclib | Up to 4 days | Median (min,max) of Cyclin D3 expression of palbociclib by study part and dose level |
| CDK4 Expression of Palbociclib | Up to 4 days | Median (min,max) of CDK4 expression of palbociclib by study part and dose level |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Stratum 1 With 50 mg/m^2 Patients known to be CNS3 at study entry may receive ITT on Day 1 rather than IT ARAC. | 6 |
| Stratum PK With 50 mg/m^2 Patients known to be CNS3 at study entry may receive ITT on Day 1 rather than IT ARAC. | 6 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Stratum 1 With 50 mg/m^2 | Stratum PK With 50 mg/m^2 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 5 Participants | 6 Participants | 11 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Continuous | 10 years | 10 years | 10 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 6 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) White | 2 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 6 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 6 | 1 / 6 |
| other Total, other adverse events | 6 / 6 | 6 / 6 |
| serious Total, serious adverse events | 6 / 6 | 6 / 6 |
Outcome results
Primary
Area Under the Drug Concentration Curve of Palbociclib
The median (min, max) of the area under the drug concentration curve for Palbociclib determined by measures at 0, 1, 2, 4, 8, and 24 hours post-dose on day 11 by study part and dose level.
Time frame: Up to 11 days
Population: All enrolled patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stratum 1 With 50 mg/m^2 | Area Under the Drug Concentration Curve of Palbociclib | 1278.5 hr*ng/mL |
| Stratum PK With 50 mg/m^2 | Area Under the Drug Concentration Curve of Palbociclib | 1131.5 hr*ng/mL |
Primary
Clearance of Palbociclib
Median (min, max) of the clearance of Palbociclib determined by measures at 0, 1, 2, 4, 8, and 24 hours post-dose on day 11 by study part and dose level
Time frame: Up to 11 days
Population: All enrolled patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stratum 1 With 50 mg/m^2 | Clearance of Palbociclib | 39.4 L/h/m^2 |
| Stratum PK With 50 mg/m^2 | Clearance of Palbociclib | 42.65 L/h/m^2 |
Primary
Frequency of Adverse Events of Palbociclib
The frequency (%) of patients experiencing adverse events at least possibly attributable to Palbociclib by study part and dose level.
Time frame: Up to 26 months
Population: All enrolled patients
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stratum 1 With 50 mg/m^2 | Frequency of Adverse Events of Palbociclib | 5 Participants |
| Stratum PK With 50 mg/m^2 | Frequency of Adverse Events of Palbociclib | 5 Participants |
Primary
Frequency of Dose Limiting Toxicities of Palbociclib
The frequency (%) of patients experiencing a cycle 1 dose limiting toxicity at least possibly attributable to Palbociclib by study part and dose level.
Time frame: Up to 32 days
Population: All enrolled patients
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stratum 1 With 50 mg/m^2 | Frequency of Dose Limiting Toxicities of Palbociclib | 1 Participants |
| Stratum PK With 50 mg/m^2 | Frequency of Dose Limiting Toxicities of Palbociclib | 0 Participants |
Primary
Half-life of Palbociclib
The median (min, max) of the half-life of Palbociclib determined by measures at 0, 1, 2, 4, 8, and 24 hours post-dose on day 11 by study part and dose level.
Time frame: Up to 11 days
Population: All enrolled patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stratum 1 With 50 mg/m^2 | Half-life of Palbociclib | 23.04 Hours |
| Stratum PK With 50 mg/m^2 | Half-life of Palbociclib | 16.78 Hours |
Primary
Maximum Serum Concentration of Palbociclib
Median (min, max) of the maximum serum concentration of Palbociclib determined by measures at 0, 1, 2, 4, 8, and 24 hours post-dose on day 11 by study part and dose level
Time frame: Up to 11 days
Population: All enrolled patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stratum 1 With 50 mg/m^2 | Maximum Serum Concentration of Palbociclib | 70.8 ng/mL |
| Stratum PK With 50 mg/m^2 | Maximum Serum Concentration of Palbociclib | 82.15 ng/mL |
Primary
Time to Reach Maximum Serum Concentration of Palbociclib
Median (min, max) of the maximum time to reach serum concentration of Palbociclib determined by measures at 0, 1, 2, 4, 8, and 24 hours post-dose on day 11 by study part and dose level
Time frame: Up to 11 days
Population: All enrolled patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stratum 1 With 50 mg/m^2 | Time to Reach Maximum Serum Concentration of Palbociclib | 3.71 Hours |
| Stratum PK With 50 mg/m^2 | Time to Reach Maximum Serum Concentration of Palbociclib | 4 Hours |
Secondary
Absolute Peripheral Blast Count of Palbociclib
Median (min, max) of absolute peripheral blast count of palbociclib by study part and dose level
Time frame: Up to 3 days
Population: All eligible patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stratum 1 With 50 mg/m^2 | Absolute Peripheral Blast Count of Palbociclib | 43 peripheral blasts per microliter |
| Stratum PK With 50 mg/m^2 | Absolute Peripheral Blast Count of Palbociclib | 54 peripheral blasts per microliter |
Secondary
CDK4 Expression of Palbociclib
Median (min,max) of CDK4 expression of palbociclib by study part and dose level
Time frame: Up to 4 days
Population: All eligible patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stratum 1 With 50 mg/m^2 | CDK4 Expression of Palbociclib | 10.7 mean fluorescence intensity (MFI) |
| Stratum PK With 50 mg/m^2 | CDK4 Expression of Palbociclib | 5.8 mean fluorescence intensity (MFI) |
Secondary
CDK6 Expression of Palbociclib
Median (min,max) of CDK6 expression of palbociclib by study part and dose level
Time frame: Up to 4 days
Population: All eligible patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stratum 1 With 50 mg/m^2 | CDK6 Expression of Palbociclib | 11.99 mean fluorescence intensity (MFI) |
| Stratum PK With 50 mg/m^2 | CDK6 Expression of Palbociclib | 13.96 mean fluorescence intensity (MFI) |
Secondary
Cyclin D3 Expression of Palbociclib
Median (min,max) of Cyclin D3 expression of palbociclib by study part and dose level
Time frame: Up to 4 days
Population: All eligible patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stratum 1 With 50 mg/m^2 | Cyclin D3 Expression of Palbociclib | 20.7 mean fluorescence intensity (MFI) |
| Stratum PK With 50 mg/m^2 | Cyclin D3 Expression of Palbociclib | 9.6 mean fluorescence intensity (MFI) |
Secondary
DAPI Biological Activity of Palbociclib
Median (min,max) of DAPI biological activity of palbociclib by study part and dose level
Time frame: up to 26 months
Population: Data not collected
Secondary
Ki67 Biological Activity of Palbociclib
Median (min,max) of CD1a biological activity of palbociclib
Time frame: Up to 32 days
Population: All eligible patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stratum 1 With 50 mg/m^2 | Ki67 Biological Activity of Palbociclib | 0.70 percentage of positive cells |
| Stratum PK With 50 mg/m^2 | Ki67 Biological Activity of Palbociclib | 13 percentage of positive cells |
Secondary
Number of Participants With at Least Partial Response to Palbociclib
Frequency (%) of patients with at least partial response to Palbociclib per leukemia/lymphoma specific response criteria: Complete Response (CR), M1 marrow (\<5% blasts) and absolute neutrophil count (ANC) at least 500/uL and platelet count at least 50000/uL without transfusion for 7 days; Complete response with incomplete recovery (CRi), M1 marrow (\<5% blasts), ANC\<500uL, platelet count \<50,000uL; Partial Response (PR), Complete disappearance of circulating blasts and achievement of M2 marrow status if M3 originally, without new sites of extramedullary disease, and with ANC ≥ 500/µL. Complete response in the marrow without resolution of extramedullary sites. Overall Response (OR) = CR+CRi+PR
Time frame: up to 26 months
Population: All enrolled patients
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stratum 1 With 50 mg/m^2 | Number of Participants With at Least Partial Response to Palbociclib | 4 Participants |
| Stratum PK With 50 mg/m^2 | Number of Participants With at Least Partial Response to Palbociclib | 1 Participants |
Secondary
p27Kip1 Expression of Palbociclib
Median (min,max) of p27Kip1 expression of palbociclib by study part and dose level
Time frame: Up to 4 days
Population: All eligible patients. Data not collected for Stratum 1 patients.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stratum 1 With 50 mg/m^2 | p27Kip1 Expression of Palbociclib | 11 Percent of cells expressing p27kip1 |
Secondary
Phospho-RB1 Expression of Palbociclib
Median (min,max) of Phospho-RB1 expression of palbociclib by study part and dose level
Time frame: Up to 4 days
Population: All eligible patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stratum 1 With 50 mg/m^2 | Phospho-RB1 Expression of Palbociclib | 13 Percent of cells expressing Phospho-RB1 |
| Stratum PK With 50 mg/m^2 | Phospho-RB1 Expression of Palbociclib | 15 Percent of cells expressing Phospho-RB1 |
Secondary
Radiographic Response of Palbociclib in Patients With LL Patients
Number of LL patients with radiographic response by study part and dose level. Complete Response (CR): Disappearance of all disease; Partial Response (PR): 50% decrease in SPD (the sum of the products of the largest diameter and the perpendicular diameter for a tumor mass). Total responders = CR+PR
Time frame: Day 32
Population: LL patients only
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stratum 1 With 50 mg/m^2 | Radiographic Response of Palbociclib in Patients With LL Patients | 0 Participants |
| Stratum PK With 50 mg/m^2 | Radiographic Response of Palbociclib in Patients With LL Patients | 0 Participants |
Secondary
RB1 Expression of Palbociclib
Median (min,max) of RB1 expression of palbociclib by study part and dose level
Time frame: Up to 4 days
Population: Data not collected