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A Study Of PF-06747143, As Single Agent Or In Combination With Standard Chemotherapy In Adult Patients With Acute Myeloid Leukemia

Sponsor
Pfizer (Industry)
Overall Status
Terminated
CT.gov ID
NCT02954653
Collaborator
(none)
8
Enrollment
4
Locations
4
Arms
12.2
Actual Duration (Months)
2
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Two part, dose escalation and dose expansion study. Open label, multi center, non randomized, multiple dose, safety, pharmacokinetic and pharmacodynamic study of single agent PF-06747143 in sequential dose levels of adult patients with refractory or relapsed AML in order to establish maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D) or maximally permitted dose (MPD) following by a 3 arm dose expansion with PF-06747143 in combination with standard of care chemotherapy in adult patients with AML.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

Patients will receive intravenous (IV) PF-06747143 as a weekly infusion (QW) in 28 day cycles at escalating doses. The proposed dosing scheme includes 0.3, 1.0, 3.0, 10, 15, and 20 mg/kg. Patients will be monitored for dose limiting toxicity (DLT) in the dose escalation in order to define the MTD. Two of the three arms in the dose expansion will include PF-06747143 in combination with standard of care chemotherapy and will include a safety lead in. The third arm, pending clinical data, will be PF-06747143 as a single agent.

Study Design

Study Type:
Interventional
Actual Enrollment :
8 participants
Allocation:
Non-Randomized
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A PHASE 1 DOSE ESCALATION STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS AND PHARMACODYNAMICS OF INTRAVENOUS PF-06747143, ADMINISTERED AS SINGLE AGENT OR IN COMBINATION WITH STANDARD CHEMOTHERAPY IN ADULT PATIENTS WITH ACUTE MYELOID LEUKEMIA
Actual Study Start Date :
Nov 28, 2016
Actual Primary Completion Date :
Dec 5, 2017
Actual Study Completion Date :
Dec 5, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Dose Escalation

Single agent PF-06747143 dose escalation

Biological: PF-06747143
PF 06747143 is a humanized IgG1 monoclonal antibody (mAb) that is an antagonist of CXCR4.
Active Comparator: Cohort 1

PF-06747143 with standard dose cytarabine and daunorubicin.

Biological: PF-06747143
PF 06747143 is a humanized IgG1 monoclonal antibody (mAb) that is an antagonist of CXCR4.

Drug: Cytarabine
100-200 mg/m2 continuous infusion for 7 days)

Drug: Daunorubicin
60-90 mg/m2 daily for 3 days
Active Comparator: Cohort 2

PF-06747143 in combination with Azacitidine or Decitabine.

Biological: PF-06747143
PF 06747143 is a humanized IgG1 monoclonal antibody (mAb) that is an antagonist of CXCR4.

Drug: Azacitidine
75 mg/m2 sub-cutaneous or intravenous for 7 days)

Drug: Decitabine
20 mg/m2 continuous intravenous infusion for 5 days in a 4-week schedule
Experimental: Cohort 3

PF-06747143 dose expansion as a single agent.

Biological: PF-06747143
PF 06747143 is a humanized IgG1 monoclonal antibody (mAb) that is an antagonist of CXCR4.

Outcome Measures

Primary Outcome Measures

  1. Number of Participants With Dose-Limiting Toxicities (DLTs) [Part 1] [Day 1 to Day 28 of Cycle 1]

    DLTs were classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 and were defined as any of a predefined set of unacceptable hematologic and non-hematologic adverse events (AEs) occurring in the first treatment cycle unless clearly determined unrelated to PF-06747143. In addition, clinically important or persistent toxicities that were not included in the pre-specified criteria could be considered a DLT following review by the investigators and sponsor.

  2. Number of Participants With Treatment-Emergent Adverse Events (AEs) [Part 2] [1 year]

    An AE was any untoward medical occurrence in a participant administered a product or medical device without regard to possibility of causal relationship. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment.

  3. Number of Participants With Laboratory Abnormalities [Part 2] [1 year]

    Following parameters were to be analyzed for laboratory examination: hematology (hemoglobin, platelets, white blood cell [WBC], absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils, absolute basophils, percent blast cells); chemistry (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen or urea, creatinine, uric acid, glucose [non-fasted], albumin, phosphorous or phosphate); coagulation (prothrombin time [PT] or international normalized ratio [INR], partial thromboplastin time [PTT] or activated PTT [aPTT]); urinalysis (urine dipstick for urine protein: if positive collect 24 hours and microscopic [reflex testing]; urine dipstick for urine blood: if positive collect a microscopic [reflex testing]); pregnancy test (for female participants of childbearing potential, serum or urine).

  4. Objective Response Rate (ORR) - Percentage of Participants With Objective Response [Part 2] [16 weeks]

    Objective Response was defined as morphologic leukemia-free state (MLFS), complete remission (CR), cytogenetic CR (CRc), molecular CR (CRm), partial remission (PR), or CR or PR with incomplete blood count recovery (CRi or PRi). MLFS: Bone marrow (BM) blasts <5%; absence of blasts with Auer rods and extramedullary disease (EMD). CR: MLFS criteria; absolute neutrophil count (ANC)>1000/ul and platelet >100,000/ul; independence from red cell transfusions. CRc: Reversion to a normal karyotype at the time of CR in cases with an abnormal karyotype at the time of diagnosis; based on the evaluation of 20 metaphase cells from BM. CRm: Reversion to a molecular-negative phenotype at the time of CR. CRi: All CR criteria except for ANC <1000/ul or platelet <100,000/ul. PR: ANC >1000/ul and platelet >100,000/ul; BM blasts decreased to 5-25% and ≥50% decrease from pre-treatment levels. PRi: ANC <1000/ul or platelet <100,000/ul; BM blasts decreased to 5-25% and ≥50% decrease from pre-treatment levels.

  5. Duration of Objective Response Rate (ORR) [Part 2] [16 weeks]

    Duration of ORR is the time from first documentation of MLFS, CR, CRc, CRm, PR, CRi or PRi to date of first documentation of disease progression or death due to any cause. MLFS: BM blasts <5%; absence of blasts with Auer rods and EMD. CR: MLFS criteria; ANC>1000/ul and platelet >100,000/ul; independence from red cell transfusions. CRc: Reversion to a normal karyotype at the time of CR in cases with an abnormal karyotype at the time of diagnosis; based on the evaluation of 20 metaphase cells from BM. CRm: Reversion to a molecular-negative phenotype at the time of CR. CRi: All CR criteria except for ANC <1000/ul or platelet <100,000/ul. PR: ANC >1000/ul and platelet >100,000/ul; BM blasts decreased to 5-25% and ≥50% decrease from pre-treatment levels. PRi: ANC <1000/ul or platelet <100,000/ul; BM blasts decreased to 5-25% and ≥50% decrease from pre-treatment levels. Disease progression/relapse: BM blast ≥5%; or reappearance of blast in the blood; or development of EMD.

  6. Progression Free Survival [Part 2] [16 weeks]

    Progression/relapse free survival is the time from the start of study treatment to first documentation of disease progression or to death due to any cause, whichever occurrs first. Disease progression/relapse: Bone marrow blast ≥ 5%; or reappearance of blast in the blood; or development of extramedullary disease (EMD).

Secondary Outcome Measures

  1. Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [Part 1] [1 year]

    An AE was any untoward medical occurrence in a participant administered a product or medical device without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening experience (immediate risk of dying); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. AEs included non-serious AEs and SAEs. Causality to study treatment was determined by the investigator.

  2. Number of Participants With Treatment-Emergent Adverse Events (AEs) by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Part 1] [1 year]

    An AE was any untoward medical occurrence in a participant administered a product or medical device without regard to possibility of causal relationship. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. AEs were graded by the investigator according to NCI CTCAE version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE). AEs included non-serious AEs and SAEs.

  3. Number of Participants With Hematology Laboratory Abnormalities by Type and Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Part 1] [1 year]

    Hematology laboratory abnormalities included anemia, hemoglobin increased, lymphocyte count increased, lymphopenia, neutrophil count decreased, platelet count decreased, and white blood cell (WBC) decreased. Each laboratory parameter was graded per NCI CTCAE version 4.03.

  4. Number of Participants With Chemistry Laboratory Abnormalities by Type and Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Part 1] [1 year]

    Chemistry laboratory abnormalities included alanine aminotransferase (ALT), alkaline phosphatase, aspartate aminotransferase (AST), bilirubin (total), creatinine, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, and hypophosphatemia. Each laboratory parameter was graded per NCI CTCAE version 4.03.

  5. Objective Response Rate (ORR) - Percentage of Participants With Objective Response [Part 1] [16 weeks]

    Objective Response was defined as morphologic leukemia-free state (MLFS), complete remission (CR), cytogenetic CR (CRc), molecular CR (CRm), partial remission (PR), or CR or PR with incomplete blood count recovery (CRi or PRi). MLFS: Bone marrow (BM) blasts <5%; absence of blasts with Auer rods and extramedullary disease (EMD). CR: MLFS criteria; absolute neutrophil count (ANC)>1000/ul and platelet >100,000/ul; independence from red cell transfusions. CRc: Reversion to a normal karyotype at the time of CR in cases with an abnormal karyotype at the time of diagnosis; based on the evaluation of 20 metaphase cells from BM. CRm: Reversion to a molecular-negative phenotype at the time of CR. CRi: All CR criteria except for ANC <1000/ul or platelet <100,000/ul. PR: ANC >1000/ul and platelet >100,000/ul; BM blasts decreased to 5-25% and ≥50% decrease from pre-treatment levels. PRi: ANC <1000/ul or platelet <100,000/ul; BM blasts decreased to 5-25% and ≥50% decrease from pre-treatment levels.

  6. Duration of Objective Response Rate (ORR) [Part 1] [16 weeks]

    Duration of ORR is the time from first documentation of MLFS, CR, CRc, CRm, PR, CRi or PRi to date of first documentation of disease progression or death due to any cause. MLFS: BM blasts <5%; absence of blasts with Auer rods and EMD. CR: MLFS criteria; ANC>1000/ul and platelet >100,000/ul; independence from red cell transfusions. CRc: Reversion to a normal karyotype at the time of CR in cases with an abnormal karyotype at the time of diagnosis; based on the evaluation of 20 metaphase cells from BM. CRm: Reversion to a molecular-negative phenotype at the time of CR. CRi: All CR criteria except for ANC <1000/ul or platelet <100,000/ul. PR: ANC >1000/ul and platelet >100,000/ul; BM blasts decreased to 5-25% and ≥50% decrease from pre-treatment levels. PRi: ANC <1000/ul or platelet <100,000/ul; BM blasts decreased to 5-25% and ≥50% decrease from pre-treatment levels. Disease progression/relapse: BM blast ≥5%; or reappearance of blast in the blood; or development of EMD.

  7. Progression Free Survival [Part 1] [16 weeks]

    Progression/relapse free survival is the time from the start of study treatment to first documentation of disease progression or to death due to any cause, whichever occurrs first. Disease progression/relapse: Bone marrow blast ≥ 5%; or reappearance of blast in the blood; or development of extramedullary disease (EMD).

  8. Incidence of Anti-Drug Antibodies (ADA) Against PF-06747143 [Part 1] [Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, end of treatment]

    Samples were tested for ADA using a validated assay. Number of participants with positive ADA samples was determined.

  9. Incidence of Neutralizing Antibodies (Nab) Against PF-06747143 [Part 1] [Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, end of treatment]

    Samples tested positive for ADA were to be further analyzed for Nab using a validated assay.

  10. Incidence of Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (Nab) Against PF-06747143 [Part 2] [Days 1 and 15 pre-dose of Cycle 1, Day 1 pre-dose of Cycles 2-6, Day 1 pre-dose of every 3 cycles thereafter, and at end of treatment]

    Samples were to be analyzed for ADA using a validated assay. ADA positive samples were to be further analyzed for Nab using a validated assay.

  11. Maximum Observed Serum Concentration (Cmax) of PF-06747143 [Parts 1 and 2] [Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment]

    Cmax of PF-06747143 was the peak serum concentration to be observed directly from data.

  12. Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-06747143 [Parts 1 and 2] [Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment]

    Tmax of PF-06747143 was to be observed directly from data as time of first occurrence of peak serum concentration.

  13. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06747143 [Parts 1 and 2] [Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment]

    AUClast is area under the serum concentration versus time profile from time zero to the time of the last quantifiable concentration.

  14. Area Under the Curve From Time Zero to Infinity (AUCinf) of PF-06747143 [Parts 1 and 2] [Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment]

    AUCinf is area under the serum concentration versus time profile from time zero extrapolated to infinite time. If data permitted, AUCinf was to be estimated.

  15. Apparent Volume of Distribution (Vd) of PF-06747143 [Parts 1 and 2] [Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment]

    Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.

  16. Terminal Elimination Half-Life (t1/2) of PF-06747143 [Parts 1 and 2] [Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment]

    t1/2 is the time measured for the serum concentration to decrease by one half. If data permitted, t1/2 was to be estimated.

  17. Clearance (CL) of PF-06747143 [Parts 1 and 2] [Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment]

    CL is a quantitative measure of the rate at which a drug substance is removed from the body.

  18. Maximum Serum Concentration at Steady State (Cmax,ss) of PF-06747143 [Parts 1 and 2] [Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment]

    Assuming steady state was achieved, Cmax,ss was to be determined following multiple dosing to characterize the PK.

  19. Minimum Observed Serum Trough Concentration at Steady State (Cmin,ss) of PF-06747143 [Parts 1 and 2] [Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment]

    Cmin is the minimum observed serum concentration. Assuming steady state was achieved, Cmin,ss was to be determined following multiple dosing to characterize the PK.

  20. Area Under the Curve From Time Zero to End of Dosing Interval at Steady State (AUCtau,ss) of PF-06747143 [Parts 1 and 2] [Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment]

    AUCtau is area under the serum concentration versus time profile from time zero to the time tau (ie, dosing interval). Assuming steady state was achieved, AUCtau,ss was to be determined following multiple dosing to characterize the PK.

  21. Accumulation Ratio (Rac) of PF-06747143 [Parts 1 and 2] [Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment]

    Accumulation ratio (Rac) was to be obtained from AUCtau at steady state (AUCtau,ss) divided by AUCtau after single dose.

  22. Clearance (CL) at Steady State of PF-06747143 [Parts 1 and 2] [Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment]

    If data permitted, CL was to be determined following multiple dosing to characterize the PK.

  23. Volume of Distribution at Steady State (Vss) at of PF-06747143 [Parts 1 and 2] [Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment]

    Vss is the apparent volume of distribution at steady-state. If data permitted, Vss was to be determined following multiple dosing to characterize the PK.

  24. Terminal Elimination Half-Life (t1/2) at Steady State of PF-06747143 [Parts 1 and 2] [Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment]

    t1/2 is the time measured for the serum concentration to decrease by one half.

  25. Peak and Trough PF-06747143 Concentrations for Selected Doses [Part 2] [Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment]

    Peak and trough PF-06747143 concentrations were to be observed directly from data.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

Part 1 and Part 2 cohort 3: Patients diagnosed with AML ( bone marrow (BM) or peripheral blood (PB) blast counts >/= 20%) and have received prior chemotherapy and/or standard of care and have relapsed, refractory or Minimal Residual Disease (defined as patients showing residual blast 10-14 days post-induction chemotherapy).

• Patients that are not candidates to receive standard of care and/or refusing the standard care of therapies will also be considered.

Part 2 - Cohort 1 and 2: Newly diagnosed, previously untreated de novo or secondary AML population (AML with bone marrow or peripheral blast counts 20%):

  • Cohort 1: Fit to receive intensive remission induction chemotherapy.

  • Cohort 2: Unfit to receive or not considered a candidate for intensive remission induction chemotherapy.

Part 1 and 2:

  • Life expectancy at least 12 weeks.

  • Hydroxyurea is allowed on study to control total peripheral white blood cell count but must be ceased 24 hours prior to first dose.

  • Off of prior therapy for 2-4 weeks prior to first dose.

  • ECOG performance status: 0 to 2.

  • Resolved acute effects of any prior therapy.

  • Adequate renal and hepatic function.

Exclusion Criteria:

  • Patients with acute promyelocytic leukemia, AML with known central nervous system (CNS) involvement unless the patient has completed treatment for the CNS disease, has recovered from the acute effects of therapy prior to study entry, and is neurologically stable.

  • Patient is known refractory to platelet or packed red cell transfusions per institutional guidelines.

  • Prior treatment with a compound targeting CXCR4.

  • Chronic systemic corticosteroid treatment.

  • Known or suspected hypersensitivity to recombinant human proteins.

  • Chronic graft versus host disease (GVHD), active GVHD with other than Grade 1 skin involvement, or GVHD requiring systemic immunosuppressive treatment (Part 1 and cohort 3).

  • Not recovered from stem cell transplant associated toxicities (Part 1 and cohort 3).

  • Prior treatment with hypomethylating agents or chemotherapy for antecedent myelodysplastic syndrome (MDS) (Part 2, cohort 2)

  • AML associated with favorable risk karyotypes, including inv(16), t(8;21), t(16;16), or t(15;17) (cohort 2)

  • Candidates for allogeneic stem cell transplant (Part 2, cohort 2)

  • Known hypersensitivity to cytarabine or daunorubicin (Part 2, cohort 1) and decitabine or azacitidine or mannitol (Part 2, cohort 2).

Contacts and Locations

Locations

Site City State Country Postal Code
1 The University of Arizona Cancer Center-North Campus Tucson Arizona United States 85719
2 Banner-University Medical Center Tucson Tucson Arizona United States 85724
3 The University of Chicago Medical Center Chicago Illinois United States 60637
4 Wake Forest Baptist Health Winston-Salem North Carolina United States 27157

Sponsors and Collaborators

  • Pfizer

Investigators

  • Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT02954653
Other Study ID Numbers:
  • B7861002
First Posted:
Nov 3, 2016
Last Update Posted:
Nov 21, 2019
Last Verified:
Nov 1, 2019
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Keywords provided by Pfizer
relapsed
refractory
acute myeloid leukemia
AML
Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Cytarabine
Azacitidine
Decitabine
Daunorubicin

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail Due to early termination of the study, the planned higher PF-06747143 dose levels (3, 10, 15, and 20 milligrams per kilogram [mg/kg]) in Part 1 were not tested; Part 2 was not conducted.
Arm/Group Title Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg Part 1: PF-06747143 at 3 mg/kg Part 1: PF-06747143 at 10 mg/kg Part 1: PF-06747143 at 15 mg/kg Part 1: PF-06747143 at 20 mg/kg Part 2: PF-06747143 at MTD/RP2D Part 2: PF-06747143 Combined With Cytarabine and Daunorubicin Part 2: PF-06747143 Combined With Azacitidine or Decitabine
Arm/Group Description PF-06747143 was administered as an intravenous infusion once weekly at 0.3 mg/kg in 28-day cycles. PF-06747143 was administered as an intravenous infusion once weekly at 1 mg/kg in 28-day cycles. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 3 mg/kg in 28-day cycles. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 15 mg/kg in 28-day cycles. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 20 mg/kg in 28-day cycles. This arm was not initiated due to early termination of the study. PF-06747143 at Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) as an intravenous infusion once weekly in 28-day cycles was optional for Part 2 and planned to be initiated in Part 2 based on single agent PF-06747143 clinical benefit in Part 1. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard intensive 7+3 chemotherapy with cytarabine (100-200 mg/m2 continuous infusion for 7 days) and daunorubicin (60-90 mg/m2 daily for 3 days) in Part 2. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard dose of azacitidine (75 mg/m2 administered subcutaneously or intravenously daily for 7 days) or decitabine (20 mg/m2 by continuous intravenous infusion over 1 hour daily for 5 days in a 4-week schedule) in Part 2.
Period Title: Overall Study
STARTED 4 4 0 0 0 0 0 0 0
Received Treatment 3 4 0 0 0 0 0 0 0
COMPLETED 0 1 0 0 0 0 0 0 0
NOT COMPLETED 4 3 0 0 0 0 0 0 0

Baseline Characteristics

Arm/Group Title Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg Total
Arm/Group Description PF-06747143 was administered as an intravenous infusion once weekly at 0.3 mg/kg in 28-day cycles. PF-06747143 was administered as an intravenous infusion once weekly at 1 mg/kg in 28-day cycles. Total of all reporting groups
Overall Participants 3 4 7
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
65.3
(4)
63.8
(14.4)
64.4
(10.5)
Age, Customized (Count of Participants)
18-44 years
0
0%
1
25%
1
14.3%
45-64 years
2
66.7%
0
0%
2
28.6%
Greater than or equal to (>=) 65 years
1
33.3%
3
75%
4
57.1%
Sex: Female, Male (Count of Participants)
Female
2
66.7%
3
75%
5
71.4%
Male
1
33.3%
1
25%
2
28.6%
Race/Ethnicity, Customized (Count of Participants)
White
3
100%
4
100%
7
100%

Outcome Measures

1. Primary Outcome
Title Number of Participants With Dose-Limiting Toxicities (DLTs) [Part 1]
Description DLTs were classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 and were defined as any of a predefined set of unacceptable hematologic and non-hematologic adverse events (AEs) occurring in the first treatment cycle unless clearly determined unrelated to PF-06747143. In addition, clinically important or persistent toxicities that were not included in the pre-specified criteria could be considered a DLT following review by the investigators and sponsor.
Time Frame Day 1 to Day 28 of Cycle 1

Outcome Measure Data

Analysis Population Description
All enrolled participants who received at least 1 dose of study treatment.
Arm/Group Title Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg
Arm/Group Description PF-06747143 was administered as an intravenous infusion once weekly at 0.3 mg/kg in 28-day cycles. PF-06747143 was administered as an intravenous infusion once weekly at 1 mg/kg in 28-day cycles.
Measure Participants 3 4
Count of Participants [Participants]
0
0%
1
25%
2. Primary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (AEs) [Part 2]
Description An AE was any untoward medical occurrence in a participant administered a product or medical device without regard to possibility of causal relationship. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment.
Time Frame 1 year

Outcome Measure Data

Analysis Population Description
No data to report as Part 2 was not conducted.
Arm/Group Title Part 2: PF-06747143 at MTD/RP2D Part 2: PF-06747143 Combined With Cytarabine and Daunorubicin Part 2: PF-06747143 Combined With Azacitidine or Decitabine
Arm/Group Description This arm was not initiated due to early termination of the study. PF-06747143 at Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) as an intravenous infusion once weekly in 28-day cycles was optional for Part 2 and planned to be initiated in Part 2 based on single agent PF-06747143 clinical benefit in Part 1. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard intensive 7+3 chemotherapy with cytarabine (100-200 mg/m2 continuous infusion for 7 days) and daunorubicin (60-90 mg/m2 daily for 3 days) in Part 2. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard dose of azacitidine (75 mg/m2 administered subcutaneously or intravenously daily for 7 days) or decitabine (20 mg/m2 by continuous intravenous infusion over 1 hour daily for 5 days in a 4-week schedule) in Part 2.
Measure Participants 0 0 0
3. Primary Outcome
Title Number of Participants With Laboratory Abnormalities [Part 2]
Description Following parameters were to be analyzed for laboratory examination: hematology (hemoglobin, platelets, white blood cell [WBC], absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils, absolute basophils, percent blast cells); chemistry (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen or urea, creatinine, uric acid, glucose [non-fasted], albumin, phosphorous or phosphate); coagulation (prothrombin time [PT] or international normalized ratio [INR], partial thromboplastin time [PTT] or activated PTT [aPTT]); urinalysis (urine dipstick for urine protein: if positive collect 24 hours and microscopic [reflex testing]; urine dipstick for urine blood: if positive collect a microscopic [reflex testing]); pregnancy test (for female participants of childbearing potential, serum or urine).
Time Frame 1 year

Outcome Measure Data

Analysis Population Description
No data to report as Part 2 was not conducted.
Arm/Group Title Part 2: PF-06747143 at MTD/RP2D Part 2: PF-06747143 Combined With Cytarabine and Daunorubicin Part 2: PF-06747143 Combined With Azacitidine or Decitabine
Arm/Group Description This arm was not initiated due to early termination of the study. PF-06747143 at Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) as an intravenous infusion once weekly in 28-day cycles was optional for Part 2 and planned to be initiated in Part 2 based on single agent PF-06747143 clinical benefit in Part 1. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard intensive 7+3 chemotherapy with cytarabine (100-200 mg/m2 continuous infusion for 7 days) and daunorubicin (60-90 mg/m2 daily for 3 days) in Part 2. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard dose of azacitidine (75 mg/m2 administered subcutaneously or intravenously daily for 7 days) or decitabine (20 mg/m2 by continuous intravenous infusion over 1 hour daily for 5 days in a 4-week schedule) in Part 2.
Measure Participants 0 0 0
4. Primary Outcome
Title Objective Response Rate (ORR) - Percentage of Participants With Objective Response [Part 2]
Description Objective Response was defined as morphologic leukemia-free state (MLFS), complete remission (CR), cytogenetic CR (CRc), molecular CR (CRm), partial remission (PR), or CR or PR with incomplete blood count recovery (CRi or PRi). MLFS: Bone marrow (BM) blasts <5%; absence of blasts with Auer rods and extramedullary disease (EMD). CR: MLFS criteria; absolute neutrophil count (ANC)>1000/ul and platelet >100,000/ul; independence from red cell transfusions. CRc: Reversion to a normal karyotype at the time of CR in cases with an abnormal karyotype at the time of diagnosis; based on the evaluation of 20 metaphase cells from BM. CRm: Reversion to a molecular-negative phenotype at the time of CR. CRi: All CR criteria except for ANC <1000/ul or platelet <100,000/ul. PR: ANC >1000/ul and platelet >100,000/ul; BM blasts decreased to 5-25% and ≥50% decrease from pre-treatment levels. PRi: ANC <1000/ul or platelet <100,000/ul; BM blasts decreased to 5-25% and ≥50% decrease from pre-treatment levels.
Time Frame 16 weeks

Outcome Measure Data

Analysis Population Description
Part 2 was not conducted.
Arm/Group Title Part 2: PF-06747143 at MTD/RP2D Part 2: PF-06747143 Combined With Cytarabine and Daunorubicin Part 2: PF-06747143 Combined With Azacitidine or Decitabine
Arm/Group Description This arm was not initiated due to early termination of the study. PF-06747143 at Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) as an intravenous infusion once weekly in 28-day cycles was optional for Part 2 and planned to be initiated in Part 2 based on single agent PF-06747143 clinical benefit in Part 1. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard intensive 7+3 chemotherapy with cytarabine (100-200 mg/m2 continuous infusion for 7 days) and daunorubicin (60-90 mg/m2 daily for 3 days) in Part 2. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard dose of azacitidine (75 mg/m2 administered subcutaneously or intravenously daily for 7 days) or decitabine (20 mg/m2 by continuous intravenous infusion over 1 hour daily for 5 days in a 4-week schedule) in Part 2.
Measure Participants 0 0 0
5. Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [Part 1]
Description An AE was any untoward medical occurrence in a participant administered a product or medical device without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening experience (immediate risk of dying); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. AEs included non-serious AEs and SAEs. Causality to study treatment was determined by the investigator.
Time Frame 1 year

Outcome Measure Data

Analysis Population Description
All enrolled participants who received at least 1 dose of study treatment.
Arm/Group Title Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg
Arm/Group Description PF-06747143 was administered as an intravenous infusion once weekly at 0.3 mg/kg in 28-day cycles. PF-06747143 was administered as an intravenous infusion once weekly at 1 mg/kg in 28-day cycles.
Measure Participants 3 4
AE (all causality)
3
100%
4
100%
AE (treatment related)
3
100%
3
75%
SAE (all causality)
1
33.3%
3
75%
SAE (treatment related)
0
0%
1
25%
6. Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (AEs) by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Part 1]
Description An AE was any untoward medical occurrence in a participant administered a product or medical device without regard to possibility of causal relationship. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. AEs were graded by the investigator according to NCI CTCAE version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE). AEs included non-serious AEs and SAEs.
Time Frame 1 year

Outcome Measure Data

Analysis Population Description
All enrolled participants who received at least 1 dose of study treatment.
Arm/Group Title Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg
Arm/Group Description PF-06747143 was administered as an intravenous infusion once weekly at 0.3 mg/kg in 28-day cycles. PF-06747143 was administered as an intravenous infusion once weekly at 1 mg/kg in 28-day cycles.
Measure Participants 3 4
Grade 1
0
0%
0
0%
Grade 2
1
33.3%
0
0%
Grade 3
0
0%
0
0%
Grade 4
1
33.3%
3
75%
Grade 5
1
33.3%
1
25%
7. Secondary Outcome
Title Number of Participants With Hematology Laboratory Abnormalities by Type and Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Part 1]
Description Hematology laboratory abnormalities included anemia, hemoglobin increased, lymphocyte count increased, lymphopenia, neutrophil count decreased, platelet count decreased, and white blood cell (WBC) decreased. Each laboratory parameter was graded per NCI CTCAE version 4.03.
Time Frame 1 year

Outcome Measure Data

Analysis Population Description
All enrolled participants who received at least 1 dose of study treatment.
Arm/Group Title Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg
Arm/Group Description PF-06747143 was administered as an intravenous infusion once weekly at 0.3 mg/kg in 28-day cycles. PF-06747143 was administered as an intravenous infusion once weekly at 1 mg/kg in 28-day cycles.
Measure Participants 3 4
Grade 0
0
0%
0
0%
Grade 1
0
0%
0
0%
Grade 2
0
0%
1
25%
Grade 3
3
100%
3
75%
Grade 4
0
0%
0
0%
Grade 0
3
100%
4
100%
Grade 1
0
0%
0
0%
Grade 2
0
0%
0
0%
Grade 3
0
0%
0
0%
Grade 4
0
0%
0
0%
Grade 0
0
0%
4
100%
Grade 1
0
0%
0
0%
Grade 2
3
100%
0
0%
Grade 3
0
0%
0
0%
Grade 4
0
0%
0
0%
Grade 0
0
0%
0
0%
Grade 1
0
0%
0
0%
Grade 2
0
0%
1
25%
Grade 3
0
0%
1
25%
Grade 4
3
100%
2
50%
Grade 0
0
0%
0
0%
Grade 1
0
0%
0
0%
Grade 2
0
0%
0
0%
Grade 3
0
0%
0
0%
Grade 4
3
100%
4
100%
Grade 0
0
0%
0
0%
Grade 1
0
0%
0
0%
Grade 2
0
0%
0
0%
Grade 3
0
0%
0
0%
Grade 4
3
100%
4
100%
Grade 0
1
33.3%
0
0%
Grade 1
0
0%
1
25%
Grade 2
0
0%
1
25%
Grade 3
1
33.3%
1
25%
Grade 4
1
33.3%
1
25%
8. Secondary Outcome
Title Number of Participants With Chemistry Laboratory Abnormalities by Type and Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Part 1]
Description Chemistry laboratory abnormalities included alanine aminotransferase (ALT), alkaline phosphatase, aspartate aminotransferase (AST), bilirubin (total), creatinine, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, and hypophosphatemia. Each laboratory parameter was graded per NCI CTCAE version 4.03.
Time Frame 1 year

Outcome Measure Data

Analysis Population Description
All enrolled participants who received at least 1 dose of study treatment.
Arm/Group Title Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg
Arm/Group Description PF-06747143 was administered as an intravenous infusion once weekly at 0.3 mg/kg in 28-day cycles. PF-06747143 was administered as an intravenous infusion once weekly at 1 mg/kg in 28-day cycles.
Measure Participants 3 4
Grade 0
0
0%
3
75%
Grade 1
3
100%
1
25%
Grade 2
0
0%
0
0%
Grade 3
0
0%
0
0%
Grade 4
0
0%
0
0%
Grade 0
0
0%
4
100%
Grade 1
1
33.3%
0
0%
Grade 2
2
66.7%
0
0%
Grade 3
0
0%
0
0%
Grade 4
0
0%
0
0%
Grade 0
0
0%
1
25%
Grade 1
2
66.7%
3
75%
Grade 2
0
0%
0
0%
Grade 3
1
33.3%
0
0%
Grade 4
0
0%
0
0%
Grade 0
1
33.3%
2
50%
Grade 1
0
0%
1
25%
Grade 2
1
33.3%
1
25%
Grade 3
0
0%
0
0%
Grade 4
1
33.3%
0
0%
Grade 0
1
33.3%
2
50%
Grade 1
1
33.3%
1
25%
Grade 2
1
33.3%
1
25%
Grade 3
0
0%
0
0%
Grade 4
0
0%
0
0%
Grade 0
3
100%
4
100%
Grade 1
0
0%
0
0%
Grade 2
0
0%
0
0%
Grade 3
0
0%
0
0%
Grade 4
0
0%
0
0%
Grade 0
0
0%
1
25%
Grade 1
1
33.3%
2
50%
Grade 2
1
33.3%
1
25%
Grade 3
1
33.3%
0
0%
Grade 4
0
0%
0
0%
Grade 0
2
66.7%
3
75%
Grade 1
0
0%
1
25%
Grade 2
0
0%
0
0%
Grade 3
1
33.3%
0
0%
Grade 4
0
0%
0
0%
Grade 0
2
66.7%
4
100%
Grade 1
1
33.3%
0
0%
Grade 2
0
0%
0
0%
Grade 3
0
0%
0
0%
Grade 4
0
0%
0
0%
Grade 0
3
100%
4
100%
Grade 1
0
0%
0
0%
Grade 2
0
0%
0
0%
Grade 3
0
0%
0
0%
Grade 4
0
0%
0
0%
Grade 0
0
0%
1
25%
Grade 1
0
0%
1
25%
Grade 2
2
66.7%
2
50%
Grade 3
1
33.3%
0
0%
Grade 4
0
0%
0
0%
Grade 0
0
0%
2
50%
Grade 1
1
33.3%
1
25%
Grade 2
1
33.3%
1
25%
Grade 3
1
33.3%
0
0%
Grade 4
0
0%
0
0%
Grade 0
3
100%
4
100%
Grade 1
0
0%
0
0%
Grade 2
0
0%
0
0%
Grade 3
0
0%
0
0%
Grade 4
0
0%
0
0%
Grade 0
1
33.3%
1
25%
Grade 1
1
33.3%
1
25%
Grade 2
0
0%
0
0%
Grade 3
1
33.3%
2
50%
Grade 4
0
0%
0
0%
Grade 0
1
33.3%
1
25%
Grade 1
2
66.7%
3
75%
Grade 2
0
0%
0
0%
Grade 3
0
0%
0
0%
Grade 4
0
0%
0
0%
Grade 0
0
0%
2
50%
Grade 1
2
66.7%
2
50%
Grade 2
0
0%
0
0%
Grade 3
1
33.3%
0
0%
Grade 4
0
0%
0
0%
Grade 0
2
66.7%
2
50%
Grade 1
0
0%
0
0%
Grade 2
0
0%
0
0%
Grade 3
1
33.3%
2
50%
Grade 4
0
0%
0
0%
9. Secondary Outcome
Title Objective Response Rate (ORR) - Percentage of Participants With Objective Response [Part 1]
Description Objective Response was defined as morphologic leukemia-free state (MLFS), complete remission (CR), cytogenetic CR (CRc), molecular CR (CRm), partial remission (PR), or CR or PR with incomplete blood count recovery (CRi or PRi). MLFS: Bone marrow (BM) blasts <5%; absence of blasts with Auer rods and extramedullary disease (EMD). CR: MLFS criteria; absolute neutrophil count (ANC)>1000/ul and platelet >100,000/ul; independence from red cell transfusions. CRc: Reversion to a normal karyotype at the time of CR in cases with an abnormal karyotype at the time of diagnosis; based on the evaluation of 20 metaphase cells from BM. CRm: Reversion to a molecular-negative phenotype at the time of CR. CRi: All CR criteria except for ANC <1000/ul or platelet <100,000/ul. PR: ANC >1000/ul and platelet >100,000/ul; BM blasts decreased to 5-25% and ≥50% decrease from pre-treatment levels. PRi: ANC <1000/ul or platelet <100,000/ul; BM blasts decreased to 5-25% and ≥50% decrease from pre-treatment levels.
Time Frame 16 weeks

Outcome Measure Data

Analysis Population Description
All enrolled participants who received at least 1 dose of study treatment and had a baseline disease assessment.
Arm/Group Title Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg
Arm/Group Description PF-06747143 was administered as an intravenous infusion once weekly at 0.3 mg/kg in 28-day cycles. PF-06747143 was administered as an intravenous infusion once weekly at 1 mg/kg in 28-day cycles.
Measure Participants 3 4
Number [percentage of participants]
NA
NaN
NA
NaN
10. Secondary Outcome
Title Duration of Objective Response Rate (ORR) [Part 1]
Description Duration of ORR is the time from first documentation of MLFS, CR, CRc, CRm, PR, CRi or PRi to date of first documentation of disease progression or death due to any cause. MLFS: BM blasts <5%; absence of blasts with Auer rods and EMD. CR: MLFS criteria; ANC>1000/ul and platelet >100,000/ul; independence from red cell transfusions. CRc: Reversion to a normal karyotype at the time of CR in cases with an abnormal karyotype at the time of diagnosis; based on the evaluation of 20 metaphase cells from BM. CRm: Reversion to a molecular-negative phenotype at the time of CR. CRi: All CR criteria except for ANC <1000/ul or platelet <100,000/ul. PR: ANC >1000/ul and platelet >100,000/ul; BM blasts decreased to 5-25% and ≥50% decrease from pre-treatment levels. PRi: ANC <1000/ul or platelet <100,000/ul; BM blasts decreased to 5-25% and ≥50% decrease from pre-treatment levels. Disease progression/relapse: BM blast ≥5%; or reappearance of blast in the blood; or development of EMD.
Time Frame 16 weeks

Outcome Measure Data

Analysis Population Description
All enrolled participants who received at least 1 dose of study treatment and had a baseline disease assessment.
Arm/Group Title Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg
Arm/Group Description PF-06747143 was administered as an intravenous infusion once weekly at 0.3 mg/kg in 28-day cycles. PF-06747143 was administered as an intravenous infusion once weekly at 1 mg/kg in 28-day cycles.
Measure Participants 3 4
Median (Full Range) [months]
NA
NA
11. Secondary Outcome
Title Progression Free Survival [Part 1]
Description Progression/relapse free survival is the time from the start of study treatment to first documentation of disease progression or to death due to any cause, whichever occurrs first. Disease progression/relapse: Bone marrow blast ≥ 5%; or reappearance of blast in the blood; or development of extramedullary disease (EMD).
Time Frame 16 weeks

Outcome Measure Data

Analysis Population Description
All enrolled participants who received at least 1 dose of study treatment and had a baseline disease assessment.
Arm/Group Title Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg
Arm/Group Description PF-06747143 was administered as an intravenous infusion once weekly at 0.3 mg/kg in 28-day cycles. PF-06747143 was administered as an intravenous infusion once weekly at 1 mg/kg in 28-day cycles.
Measure Participants 3 4
Median (Full Range) [months]
NA
NA
12. Secondary Outcome
Title Incidence of Anti-Drug Antibodies (ADA) Against PF-06747143 [Part 1]
Description Samples were tested for ADA using a validated assay. Number of participants with positive ADA samples was determined.
Time Frame Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, end of treatment

Outcome Measure Data

Analysis Population Description
All enrolled patients who received at least 1 dose of study treatment.
Arm/Group Title Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg
Arm/Group Description PF-06747143 was administered as an intravenous infusion once weekly at 0.3 mg/kg in 28-day cycles. PF-06747143 was administered as an intravenous infusion once weekly at 1 mg/kg in 28-day cycles.
Measure Participants 3 4
Cycle 1 Day 1
0
0%
1
25%
Cycle 1 Day 15
0
0%
0
0%
Cycle 2 Day 1
0
0%
0
0%
End of treatment
0
0%
0
0%
13. Secondary Outcome
Title Incidence of Neutralizing Antibodies (Nab) Against PF-06747143 [Part 1]
Description Samples tested positive for ADA were to be further analyzed for Nab using a validated assay.
Time Frame Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, end of treatment

Outcome Measure Data

Analysis Population Description
No data was collected as Nab analysis was not performed.
Arm/Group Title Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg
Arm/Group Description PF-06747143 was administered as an intravenous infusion once weekly at 0.3 mg/kg in 28-day cycles. PF-06747143 was administered as an intravenous infusion once weekly at 1 mg/kg in 28-day cycles.
Measure Participants 0 0
14. Secondary Outcome
Title Incidence of Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (Nab) Against PF-06747143 [Part 2]
Description Samples were to be analyzed for ADA using a validated assay. ADA positive samples were to be further analyzed for Nab using a validated assay.
Time Frame Days 1 and 15 pre-dose of Cycle 1, Day 1 pre-dose of Cycles 2-6, Day 1 pre-dose of every 3 cycles thereafter, and at end of treatment

Outcome Measure Data

Analysis Population Description
Part 2 was not conducted.
Arm/Group Title Part 2: PF-06747143 at MTD/RP2D Part 2: PF-06747143 Combined With Cytarabine and Daunorubicin Part 2: PF-06747143 Combined With Azacitidine or Decitabine
Arm/Group Description This arm was not initiated due to early termination of the study. PF-06747143 at Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) as an intravenous infusion once weekly in 28-day cycles was optional for Part 2 and planned to be initiated in Part 2 based on single agent PF-06747143 clinical benefit in Part 1. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard intensive 7+3 chemotherapy with cytarabine (100-200 mg/m2 continuous infusion for 7 days) and daunorubicin (60-90 mg/m2 daily for 3 days) in Part 2. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard dose of azacitidine (75 mg/m2 administered subcutaneously or intravenously daily for 7 days) or decitabine (20 mg/m2 by continuous intravenous infusion over 1 hour daily for 5 days in a 4-week schedule) in Part 2.
Measure Participants 0 0 0
15. Secondary Outcome
Title Maximum Observed Serum Concentration (Cmax) of PF-06747143 [Parts 1 and 2]
Description Cmax of PF-06747143 was the peak serum concentration to be observed directly from data.
Time Frame Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment

Outcome Measure Data

Analysis Population Description
Due to the early termination of the study, Part 1 pharmacokinetics (PK) assessments were not completed and Part 2 was not conducted.
Arm/Group Title Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg Part 2: PF-06747143 at MTD/RP2D Part 2: PF-06747143 Combined With Cytarabine and Daunorubicin Part 2: PF-06747143 Combined With Azacitidine or Decitabine
Arm/Group Description PF-06747143 was administered as an intravenous infusion once weekly at 0.3 mg/kg in 28-day cycles. PF-06747143 was administered as an intravenous infusion once weekly at 1 mg/kg in 28-day cycles. This arm was not initiated due to early termination of the study. PF-06747143 at Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) as an intravenous infusion once weekly in 28-day cycles was optional for Part 2 and planned to be initiated in Part 2 based on single agent PF-06747143 clinical benefit in Part 1. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard intensive 7+3 chemotherapy with cytarabine (100-200 mg/m2 continuous infusion for 7 days) and daunorubicin (60-90 mg/m2 daily for 3 days) in Part 2. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard dose of azacitidine (75 mg/m2 administered subcutaneously or intravenously daily for 7 days) or decitabine (20 mg/m2 by continuous intravenous infusion over 1 hour daily for 5 days in a 4-week schedule) in Part 2.
Measure Participants 0 0 0 0 0
16. Secondary Outcome
Title Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-06747143 [Parts 1 and 2]
Description Tmax of PF-06747143 was to be observed directly from data as time of first occurrence of peak serum concentration.
Time Frame Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment

Outcome Measure Data

Analysis Population Description
Due to the early termination of the study, Part 1 PK assessments were not completed and Part 2 was not conducted.
Arm/Group Title Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg Part 2: PF-06747143 at MTD/RP2D Part 2: PF-06747143 Combined With Cytarabine and Daunorubicin Part 2: PF-06747143 Combined With Azacitidine or Decitabine
Arm/Group Description PF-06747143 was administered as an intravenous infusion once weekly at 0.3 mg/kg in 28-day cycles. PF-06747143 was administered as an intravenous infusion once weekly at 1 mg/kg in 28-day cycles. This arm was not initiated due to early termination of the study. PF-06747143 at Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) as an intravenous infusion once weekly in 28-day cycles was optional for Part 2 and planned to be initiated in Part 2 based on single agent PF-06747143 clinical benefit in Part 1. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard intensive 7+3 chemotherapy with cytarabine (100-200 mg/m2 continuous infusion for 7 days) and daunorubicin (60-90 mg/m2 daily for 3 days) in Part 2. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard dose of azacitidine (75 mg/m2 administered subcutaneously or intravenously daily for 7 days) or decitabine (20 mg/m2 by continuous intravenous infusion over 1 hour daily for 5 days in a 4-week schedule) in Part 2.
Measure Participants 0 0 0 0 0
17. Secondary Outcome
Title Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-06747143 [Parts 1 and 2]
Description AUClast is area under the serum concentration versus time profile from time zero to the time of the last quantifiable concentration.
Time Frame Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment

Outcome Measure Data

Analysis Population Description
Due to the early termination of the study, Part 1 PK assessments were not completed and Part 2 was not conducted.
Arm/Group Title Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg Part 2: PF-06747143 at MTD/RP2D Part 2: PF-06747143 Combined With Cytarabine and Daunorubicin Part 2: PF-06747143 Combined With Azacitidine or Decitabine
Arm/Group Description PF-06747143 was administered as an intravenous infusion once weekly at 0.3 mg/kg in 28-day cycles. PF-06747143 was administered as an intravenous infusion once weekly at 1 mg/kg in 28-day cycles. This arm was not initiated due to early termination of the study. PF-06747143 at Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) as an intravenous infusion once weekly in 28-day cycles was optional for Part 2 and planned to be initiated in Part 2 based on single agent PF-06747143 clinical benefit in Part 1. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard intensive 7+3 chemotherapy with cytarabine (100-200 mg/m2 continuous infusion for 7 days) and daunorubicin (60-90 mg/m2 daily for 3 days) in Part 2. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard dose of azacitidine (75 mg/m2 administered subcutaneously or intravenously daily for 7 days) or decitabine (20 mg/m2 by continuous intravenous infusion over 1 hour daily for 5 days in a 4-week schedule) in Part 2.
Measure Participants 0 0 0 0 0
18. Secondary Outcome
Title Area Under the Curve From Time Zero to Infinity (AUCinf) of PF-06747143 [Parts 1 and 2]
Description AUCinf is area under the serum concentration versus time profile from time zero extrapolated to infinite time. If data permitted, AUCinf was to be estimated.
Time Frame Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment

Outcome Measure Data

Analysis Population Description
Due to the early termination of the study, Part 1 PK assessments were not completed and Part 2 was not conducted.
Arm/Group Title Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg Part 2: PF-06747143 at MTD/RP2D Part 2: PF-06747143 Combined With Cytarabine and Daunorubicin Part 2: PF-06747143 Combined With Azacitidine or Decitabine
Arm/Group Description PF-06747143 was administered as an intravenous infusion once weekly at 0.3 mg/kg in 28-day cycles. PF-06747143 was administered as an intravenous infusion once weekly at 1 mg/kg in 28-day cycles. This arm was not initiated due to early termination of the study. PF-06747143 at Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) as an intravenous infusion once weekly in 28-day cycles was optional for Part 2 and planned to be initiated in Part 2 based on single agent PF-06747143 clinical benefit in Part 1. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard intensive 7+3 chemotherapy with cytarabine (100-200 mg/m2 continuous infusion for 7 days) and daunorubicin (60-90 mg/m2 daily for 3 days) in Part 2. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard dose of azacitidine (75 mg/m2 administered subcutaneously or intravenously daily for 7 days) or decitabine (20 mg/m2 by continuous intravenous infusion over 1 hour daily for 5 days in a 4-week schedule) in Part 2.
Measure Participants 0 0 0 0 0
19. Secondary Outcome
Title Apparent Volume of Distribution (Vd) of PF-06747143 [Parts 1 and 2]
Description Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.
Time Frame Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment

Outcome Measure Data

Analysis Population Description
Due to the early termination of the study, Part 1 PK assessments were not completed and Part 2 was not conducted.
Arm/Group Title Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg Part 2: PF-06747143 at MTD/RP2D Part 2: PF-06747143 Combined With Cytarabine and Daunorubicin Part 2: PF-06747143 Combined With Azacitidine or Decitabine
Arm/Group Description PF-06747143 was administered as an intravenous infusion once weekly at 0.3 mg/kg in 28-day cycles. PF-06747143 was administered as an intravenous infusion once weekly at 1 mg/kg in 28-day cycles. This arm was not initiated due to early termination of the study. PF-06747143 at Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) as an intravenous infusion once weekly in 28-day cycles was optional for Part 2 and planned to be initiated in Part 2 based on single agent PF-06747143 clinical benefit in Part 1. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard intensive 7+3 chemotherapy with cytarabine (100-200 mg/m2 continuous infusion for 7 days) and daunorubicin (60-90 mg/m2 daily for 3 days) in Part 2. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard dose of azacitidine (75 mg/m2 administered subcutaneously or intravenously daily for 7 days) or decitabine (20 mg/m2 by continuous intravenous infusion over 1 hour daily for 5 days in a 4-week schedule) in Part 2.
Measure Participants 0 0 0 0 0
20. Secondary Outcome
Title Terminal Elimination Half-Life (t1/2) of PF-06747143 [Parts 1 and 2]
Description t1/2 is the time measured for the serum concentration to decrease by one half. If data permitted, t1/2 was to be estimated.
Time Frame Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment

Outcome Measure Data

Analysis Population Description
Due to the early termination of the study, Part 1 PK assessments were not completed and Part 2 was not conducted.
Arm/Group Title Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg Part 2: PF-06747143 at MTD/RP2D Part 2: PF-06747143 Combined With Cytarabine and Daunorubicin Part 2: PF-06747143 Combined With Azacitidine or Decitabine
Arm/Group Description PF-06747143 was administered as an intravenous infusion once weekly at 0.3 mg/kg in 28-day cycles. PF-06747143 was administered as an intravenous infusion once weekly at 1 mg/kg in 28-day cycles. This arm was not initiated due to early termination of the study. PF-06747143 at Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) as an intravenous infusion once weekly in 28-day cycles was optional for Part 2 and planned to be initiated in Part 2 based on single agent PF-06747143 clinical benefit in Part 1. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard intensive 7+3 chemotherapy with cytarabine (100-200 mg/m2 continuous infusion for 7 days) and daunorubicin (60-90 mg/m2 daily for 3 days) in Part 2. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard dose of azacitidine (75 mg/m2 administered subcutaneously or intravenously daily for 7 days) or decitabine (20 mg/m2 by continuous intravenous infusion over 1 hour daily for 5 days in a 4-week schedule) in Part 2.
Measure Participants 0 0 0 0 0
21. Secondary Outcome
Title Clearance (CL) of PF-06747143 [Parts 1 and 2]
Description CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Time Frame Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment

Outcome Measure Data

Analysis Population Description
Due to the early termination of the study, Part 1 PK assessments were not completed and Part 2 was not conducted.
Arm/Group Title Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg Part 2: PF-06747143 at MTD/RP2D Part 2: PF-06747143 Combined With Cytarabine and Daunorubicin Part 2: PF-06747143 Combined With Azacitidine or Decitabine
Arm/Group Description PF-06747143 was administered as an intravenous infusion once weekly at 0.3 mg/kg in 28-day cycles. PF-06747143 was administered as an intravenous infusion once weekly at 1 mg/kg in 28-day cycles. This arm was not initiated due to early termination of the study. PF-06747143 at Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) as an intravenous infusion once weekly in 28-day cycles was optional for Part 2 and planned to be initiated in Part 2 based on single agent PF-06747143 clinical benefit in Part 1. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard intensive 7+3 chemotherapy with cytarabine (100-200 mg/m2 continuous infusion for 7 days) and daunorubicin (60-90 mg/m2 daily for 3 days) in Part 2. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard dose of azacitidine (75 mg/m2 administered subcutaneously or intravenously daily for 7 days) or decitabine (20 mg/m2 by continuous intravenous infusion over 1 hour daily for 5 days in a 4-week schedule) in Part 2.
Measure Participants 0 0 0 0 0
22. Secondary Outcome
Title Maximum Serum Concentration at Steady State (Cmax,ss) of PF-06747143 [Parts 1 and 2]
Description Assuming steady state was achieved, Cmax,ss was to be determined following multiple dosing to characterize the PK.
Time Frame Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment

Outcome Measure Data

Analysis Population Description
Due to the early termination of the study, Part 1 PK assessments were not completed and Part 2 was not conducted.
Arm/Group Title Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg Part 2: PF-06747143 at MTD/RP2D Part 2: PF-06747143 Combined With Cytarabine and Daunorubicin Part 2: PF-06747143 Combined With Azacitidine or Decitabine
Arm/Group Description PF-06747143 was administered as an intravenous infusion once weekly at 0.3 mg/kg in 28-day cycles. PF-06747143 was administered as an intravenous infusion once weekly at 1 mg/kg in 28-day cycles. This arm was not initiated due to early termination of the study. PF-06747143 at Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) as an intravenous infusion once weekly in 28-day cycles was optional for Part 2 and planned to be initiated in Part 2 based on single agent PF-06747143 clinical benefit in Part 1. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard intensive 7+3 chemotherapy with cytarabine (100-200 mg/m2 continuous infusion for 7 days) and daunorubicin (60-90 mg/m2 daily for 3 days) in Part 2. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard dose of azacitidine (75 mg/m2 administered subcutaneously or intravenously daily for 7 days) or decitabine (20 mg/m2 by continuous intravenous infusion over 1 hour daily for 5 days in a 4-week schedule) in Part 2.
Measure Participants 0 0 0 0 0
23. Secondary Outcome
Title Minimum Observed Serum Trough Concentration at Steady State (Cmin,ss) of PF-06747143 [Parts 1 and 2]
Description Cmin is the minimum observed serum concentration. Assuming steady state was achieved, Cmin,ss was to be determined following multiple dosing to characterize the PK.
Time Frame Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment

Outcome Measure Data

Analysis Population Description
Due to the early termination of the study, Part 1 PK assessments were not completed and Part 2 was not conducted.
Arm/Group Title Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg Part 2: PF-06747143 at MTD/RP2D Part 2: PF-06747143 Combined With Cytarabine and Daunorubicin Part 2: PF-06747143 Combined With Azacitidine or Decitabine
Arm/Group Description PF-06747143 was administered as an intravenous infusion once weekly at 0.3 mg/kg in 28-day cycles. PF-06747143 was administered as an intravenous infusion once weekly at 1 mg/kg in 28-day cycles. This arm was not initiated due to early termination of the study. PF-06747143 at Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) as an intravenous infusion once weekly in 28-day cycles was optional for Part 2 and planned to be initiated in Part 2 based on single agent PF-06747143 clinical benefit in Part 1. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard intensive 7+3 chemotherapy with cytarabine (100-200 mg/m2 continuous infusion for 7 days) and daunorubicin (60-90 mg/m2 daily for 3 days) in Part 2. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard dose of azacitidine (75 mg/m2 administered subcutaneously or intravenously daily for 7 days) or decitabine (20 mg/m2 by continuous intravenous infusion over 1 hour daily for 5 days in a 4-week schedule) in Part 2.
Measure Participants 0 0 0 0 0
24. Secondary Outcome
Title Area Under the Curve From Time Zero to End of Dosing Interval at Steady State (AUCtau,ss) of PF-06747143 [Parts 1 and 2]
Description AUCtau is area under the serum concentration versus time profile from time zero to the time tau (ie, dosing interval). Assuming steady state was achieved, AUCtau,ss was to be determined following multiple dosing to characterize the PK.
Time Frame Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment

Outcome Measure Data

Analysis Population Description
Due to the early termination of the study, Part 1 PK assessments were not completed and Part 2 was not conducted.
Arm/Group Title Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg Part 2: PF-06747143 at MTD/RP2D Part 2: PF-06747143 Combined With Cytarabine and Daunorubicin Part 2: PF-06747143 Combined With Azacitidine or Decitabine
Arm/Group Description PF-06747143 was administered as an intravenous infusion once weekly at 0.3 mg/kg in 28-day cycles. PF-06747143 was administered as an intravenous infusion once weekly at 1 mg/kg in 28-day cycles. This arm was not initiated due to early termination of the study. PF-06747143 at Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) as an intravenous infusion once weekly in 28-day cycles was optional for Part 2 and planned to be initiated in Part 2 based on single agent PF-06747143 clinical benefit in Part 1. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard intensive 7+3 chemotherapy with cytarabine (100-200 mg/m2 continuous infusion for 7 days) and daunorubicin (60-90 mg/m2 daily for 3 days) in Part 2. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard dose of azacitidine (75 mg/m2 administered subcutaneously or intravenously daily for 7 days) or decitabine (20 mg/m2 by continuous intravenous infusion over 1 hour daily for 5 days in a 4-week schedule) in Part 2.
Measure Participants 0 0 0 0 0
25. Secondary Outcome
Title Accumulation Ratio (Rac) of PF-06747143 [Parts 1 and 2]
Description Accumulation ratio (Rac) was to be obtained from AUCtau at steady state (AUCtau,ss) divided by AUCtau after single dose.
Time Frame Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment

Outcome Measure Data

Analysis Population Description
Due to the early termination of the study, Part 1 PK assessments were not completed and Part 2 was not conducted.
Arm/Group Title Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg Part 2: PF-06747143 at MTD/RP2D Part 2: PF-06747143 Combined With Cytarabine and Daunorubicin Part 2: PF-06747143 Combined With Azacitidine or Decitabine
Arm/Group Description PF-06747143 was administered as an intravenous infusion once weekly at 0.3 mg/kg in 28-day cycles. PF-06747143 was administered as an intravenous infusion once weekly at 1 mg/kg in 28-day cycles. This arm was not initiated due to early termination of the study. PF-06747143 at Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) as an intravenous infusion once weekly in 28-day cycles was optional for Part 2 and planned to be initiated in Part 2 based on single agent PF-06747143 clinical benefit in Part 1. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard intensive 7+3 chemotherapy with cytarabine (100-200 mg/m2 continuous infusion for 7 days) and daunorubicin (60-90 mg/m2 daily for 3 days) in Part 2. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard dose of azacitidine (75 mg/m2 administered subcutaneously or intravenously daily for 7 days) or decitabine (20 mg/m2 by continuous intravenous infusion over 1 hour daily for 5 days in a 4-week schedule) in Part 2.
Measure Participants 0 0 0 0 0
26. Secondary Outcome
Title Clearance (CL) at Steady State of PF-06747143 [Parts 1 and 2]
Description If data permitted, CL was to be determined following multiple dosing to characterize the PK.
Time Frame Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment

Outcome Measure Data

Analysis Population Description
Due to the early termination of the study, Part 1 PK assessments were not completed and Part 2 was not conducted.
Arm/Group Title Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg Part 2: PF-06747143 at MTD/RP2D Part 2: PF-06747143 Combined With Cytarabine and Daunorubicin Part 2: PF-06747143 Combined With Azacitidine or Decitabine
Arm/Group Description PF-06747143 was administered as an intravenous infusion once weekly at 0.3 mg/kg in 28-day cycles. PF-06747143 was administered as an intravenous infusion once weekly at 1 mg/kg in 28-day cycles. This arm was not initiated due to early termination of the study. PF-06747143 at Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) as an intravenous infusion once weekly in 28-day cycles was optional for Part 2 and planned to be initiated in Part 2 based on single agent PF-06747143 clinical benefit in Part 1. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard intensive 7+3 chemotherapy with cytarabine (100-200 mg/m2 continuous infusion for 7 days) and daunorubicin (60-90 mg/m2 daily for 3 days) in Part 2. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard dose of azacitidine (75 mg/m2 administered subcutaneously or intravenously daily for 7 days) or decitabine (20 mg/m2 by continuous intravenous infusion over 1 hour daily for 5 days in a 4-week schedule) in Part 2.
Measure Participants 0 0 0 0 0
27. Secondary Outcome
Title Volume of Distribution at Steady State (Vss) at of PF-06747143 [Parts 1 and 2]
Description Vss is the apparent volume of distribution at steady-state. If data permitted, Vss was to be determined following multiple dosing to characterize the PK.
Time Frame Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment

Outcome Measure Data

Analysis Population Description
Due to the early termination of the study, Part 1 PK assessments were not completed and Part 2 was not conducted.
Arm/Group Title Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg Part 2: PF-06747143 at MTD/RP2D Part 2: PF-06747143 Combined With Cytarabine and Daunorubicin Part 2: PF-06747143 Combined With Azacitidine or Decitabine
Arm/Group Description PF-06747143 was administered as an intravenous infusion once weekly at 0.3 mg/kg in 28-day cycles. PF-06747143 was administered as an intravenous infusion once weekly at 1 mg/kg in 28-day cycles. This arm was not initiated due to early termination of the study. PF-06747143 at Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) as an intravenous infusion once weekly in 28-day cycles was optional for Part 2 and planned to be initiated in Part 2 based on single agent PF-06747143 clinical benefit in Part 1. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard intensive 7+3 chemotherapy with cytarabine (100-200 mg/m2 continuous infusion for 7 days) and daunorubicin (60-90 mg/m2 daily for 3 days) in Part 2. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard dose of azacitidine (75 mg/m2 administered subcutaneously or intravenously daily for 7 days) or decitabine (20 mg/m2 by continuous intravenous infusion over 1 hour daily for 5 days in a 4-week schedule) in Part 2.
Measure Participants 0 0 0 0 0
28. Secondary Outcome
Title Terminal Elimination Half-Life (t1/2) at Steady State of PF-06747143 [Parts 1 and 2]
Description t1/2 is the time measured for the serum concentration to decrease by one half.
Time Frame Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment

Outcome Measure Data

Analysis Population Description
Due to the early termination of the study, Part 1 PK assessments were not completed and Part 2 was not conducted.
Arm/Group Title Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg Part 2: PF-06747143 at MTD/RP2D Part 2: PF-06747143 Combined With Cytarabine and Daunorubicin Part 2: PF-06747143 Combined With Azacitidine or Decitabine
Arm/Group Description PF-06747143 was administered as an intravenous infusion once weekly at 0.3 mg/kg in 28-day cycles. PF-06747143 was administered as an intravenous infusion once weekly at 1 mg/kg in 28-day cycles. This arm was not initiated due to early termination of the study. PF-06747143 at Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) as an intravenous infusion once weekly in 28-day cycles was optional for Part 2 and planned to be initiated in Part 2 based on single agent PF-06747143 clinical benefit in Part 1. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard intensive 7+3 chemotherapy with cytarabine (100-200 mg/m2 continuous infusion for 7 days) and daunorubicin (60-90 mg/m2 daily for 3 days) in Part 2. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard dose of azacitidine (75 mg/m2 administered subcutaneously or intravenously daily for 7 days) or decitabine (20 mg/m2 by continuous intravenous infusion over 1 hour daily for 5 days in a 4-week schedule) in Part 2.
Measure Participants 0 0 0 0 0
29. Secondary Outcome
Title Peak and Trough PF-06747143 Concentrations for Selected Doses [Part 2]
Description Peak and trough PF-06747143 concentrations were to be observed directly from data.
Time Frame Cycle 1 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 1 Day 8 at 0 hour; Cycle 1 Day 15 at 0 and 1 hour; Cycle 1 Day 22 at 0 hour; Cycle 2 Day 1 at 0, 1, 24, 48, 96 hours; Cycle 2 Days 8, 15 and 22 at 0 hour; Subsequent cycles: Day 1 at 0 hour; End of treatment

Outcome Measure Data

Analysis Population Description
Part 2 was not conducted.
Arm/Group Title Part 2: PF-06747143 at MTD/RP2D Part 2: PF-06747143 Combined With Cytarabine and Daunorubicin Part 2: PF-06747143 Combined With Azacitidine or Decitabine
Arm/Group Description This arm was not initiated due to early termination of the study. PF-06747143 at Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) as an intravenous infusion once weekly in 28-day cycles was optional for Part 2 and planned to be initiated in Part 2 based on single agent PF-06747143 clinical benefit in Part 1. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard intensive 7+3 chemotherapy with cytarabine (100-200 mg/m2 continuous infusion for 7 days) and daunorubicin (60-90 mg/m2 daily for 3 days) in Part 2. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard dose of azacitidine (75 mg/m2 administered subcutaneously or intravenously daily for 7 days) or decitabine (20 mg/m2 by continuous intravenous infusion over 1 hour daily for 5 days in a 4-week schedule) in Part 2.
Measure Participants 0 0 0
30. Primary Outcome
Title Duration of Objective Response Rate (ORR) [Part 2]
Description Duration of ORR is the time from first documentation of MLFS, CR, CRc, CRm, PR, CRi or PRi to date of first documentation of disease progression or death due to any cause. MLFS: BM blasts <5%; absence of blasts with Auer rods and EMD. CR: MLFS criteria; ANC>1000/ul and platelet >100,000/ul; independence from red cell transfusions. CRc: Reversion to a normal karyotype at the time of CR in cases with an abnormal karyotype at the time of diagnosis; based on the evaluation of 20 metaphase cells from BM. CRm: Reversion to a molecular-negative phenotype at the time of CR. CRi: All CR criteria except for ANC <1000/ul or platelet <100,000/ul. PR: ANC >1000/ul and platelet >100,000/ul; BM blasts decreased to 5-25% and ≥50% decrease from pre-treatment levels. PRi: ANC <1000/ul or platelet <100,000/ul; BM blasts decreased to 5-25% and ≥50% decrease from pre-treatment levels. Disease progression/relapse: BM blast ≥5%; or reappearance of blast in the blood; or development of EMD.
Time Frame 16 weeks

Outcome Measure Data

Analysis Population Description
Part 2 was not conducted.
Arm/Group Title Part 2: PF-06747143 at MTD/RP2D Part 2: PF-06747143 Combined With Cytarabine and Daunorubicin Part 2: PF-06747143 Combined With Azacitidine or Decitabine
Arm/Group Description This arm was not initiated due to early termination of the study. PF-06747143 at Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) as an intravenous infusion once weekly in 28-day cycles was optional for Part 2 and planned to be initiated in Part 2 based on single agent PF-06747143 clinical benefit in Part 1. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard intensive 7+3 chemotherapy with cytarabine (100-200 mg/m2 continuous infusion for 7 days) and daunorubicin (60-90 mg/m2 daily for 3 days) in Part 2. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard dose of azacitidine (75 mg/m2 administered subcutaneously or intravenously daily for 7 days) or decitabine (20 mg/m2 by continuous intravenous infusion over 1 hour daily for 5 days in a 4-week schedule) in Part 2.
Measure Participants 0 0 0
31. Primary Outcome
Title Progression Free Survival [Part 2]
Description Progression/relapse free survival is the time from the start of study treatment to first documentation of disease progression or to death due to any cause, whichever occurrs first. Disease progression/relapse: Bone marrow blast ≥ 5%; or reappearance of blast in the blood; or development of extramedullary disease (EMD).
Time Frame 16 weeks

Outcome Measure Data

Analysis Population Description
Part 2 was not conducted.
Arm/Group Title Part 2: PF-06747143 at MTD/RP2D Part 2: PF-06747143 Combined With Cytarabine and Daunorubicin Part 2: PF-06747143 Combined With Azacitidine or Decitabine
Arm/Group Description This arm was not initiated due to early termination of the study. PF-06747143 at Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) as an intravenous infusion once weekly in 28-day cycles was optional for Part 2 and planned to be initiated in Part 2 based on single agent PF-06747143 clinical benefit in Part 1. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard intensive 7+3 chemotherapy with cytarabine (100-200 mg/m2 continuous infusion for 7 days) and daunorubicin (60-90 mg/m2 daily for 3 days) in Part 2. This arm was not initiated due to early termination of the study. PF-06747143 was planned to be administered as an intravenous infusion once weekly at 10 mg/kg in 28-day cycles in combination with standard dose of azacitidine (75 mg/m2 administered subcutaneously or intravenously daily for 7 days) or decitabine (20 mg/m2 by continuous intravenous infusion over 1 hour daily for 5 days in a 4-week schedule) in Part 2.
Measure Participants 0 0 0

Adverse Events

Time Frame 1 year
Adverse Event Reporting Description The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study.
Arm/Group Title Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg
Arm/Group Description PF-06747143 was administered as an intravenous infusion once weekly at 0.3 mg/kg in 28-day cycles. PF-06747143 was administered as an intravenous infusion once weekly at 1 mg/kg in 28-day cycles.
All Cause Mortality
Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 3/3 (100%) 1/4 (25%)
Serious Adverse Events
Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 1/3 (33.3%) 3/4 (75%)
General disorders
Pyrexia 0/3 (0%) 1/4 (25%)
Infections and infestations
Cellulitis 0/3 (0%) 1/4 (25%)
Pneumonia 0/3 (0%) 1/4 (25%)
Sepsis 1/3 (33.3%) 0/4 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm progression 0/3 (0%) 1/4 (25%)
Respiratory, thoracic and mediastinal disorders
Hypoxia 1/3 (33.3%) 0/4 (0%)
Other (Not Including Serious) Adverse Events
Part 1: PF-06747143 0.3 mg/kg Part 1: PF-06747143 1 mg/kg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 3/3 (100%) 4/4 (100%)
Blood and lymphatic system disorders
Anaemia 0/3 (0%) 1/4 (25%)
Febrile neutropenia 0/3 (0%) 1/4 (25%)
Leukocytosis 1/3 (33.3%) 1/4 (25%)
Neutropenia 0/3 (0%) 1/4 (25%)
Thrombocytopenia 0/3 (0%) 2/4 (50%)
Cardiac disorders
Tachycardia 2/3 (66.7%) 2/4 (50%)
Gastrointestinal disorders
Abdominal pain 1/3 (33.3%) 0/4 (0%)
Abdominal pain lower 1/3 (33.3%) 0/4 (0%)
Constipation 1/3 (33.3%) 0/4 (0%)
Diarrhoea 2/3 (66.7%) 0/4 (0%)
Gingival bleeding 0/3 (0%) 1/4 (25%)
Lower gastrointestinal haemorrhage 0/3 (0%) 1/4 (25%)
Nausea 3/3 (100%) 2/4 (50%)
Stomatitis 0/3 (0%) 1/4 (25%)
Vomiting 1/3 (33.3%) 2/4 (50%)
General disorders
Asthenia 0/3 (0%) 1/4 (25%)
Chills 2/3 (66.7%) 2/4 (50%)
Fatigue 2/3 (66.7%) 1/4 (25%)
Malaise 1/3 (33.3%) 0/4 (0%)
Mucosal inflammation 1/3 (33.3%) 1/4 (25%)
Oedema peripheral 2/3 (66.7%) 0/4 (0%)
Pyrexia 3/3 (100%) 3/4 (75%)
Hepatobiliary disorders
Hyperbilirubinaemia 1/3 (33.3%) 0/4 (0%)
Immune system disorders
Drug hypersensitivity 1/3 (33.3%) 0/4 (0%)
Infections and infestations
Pneumonia 1/3 (33.3%) 0/4 (0%)
Sinusitis 1/3 (33.3%) 0/4 (0%)
Injury, poisoning and procedural complications
Allergic transfusion reaction 1/3 (33.3%) 0/4 (0%)
Infusion related reaction 0/3 (0%) 2/4 (50%)
Transfusion reaction 1/3 (33.3%) 0/4 (0%)
Investigations
Blood bilirubin increased 0/3 (0%) 1/4 (25%)
Blood phosphorus increased 0/3 (0%) 1/4 (25%)
Electrocardiogram QT prolonged 1/3 (33.3%) 0/4 (0%)
Hepatic enzyme increased 1/3 (33.3%) 0/4 (0%)
Lymphocyte count decreased 1/3 (33.3%) 1/4 (25%)
Oxygen saturation decreased 0/3 (0%) 1/4 (25%)
Metabolism and nutrition disorders
Decreased appetite 1/3 (33.3%) 1/4 (25%)
Hyperkalaemia 1/3 (33.3%) 0/4 (0%)
Hypocalcaemia 2/3 (66.7%) 0/4 (0%)
Hypokalaemia 0/3 (0%) 2/4 (50%)
Hypomagnesaemia 0/3 (0%) 3/4 (75%)
Hypophosphataemia 1/3 (33.3%) 2/4 (50%)
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain 1/3 (33.3%) 0/4 (0%)
Neck pain 1/3 (33.3%) 0/4 (0%)
Pain in extremity 0/3 (0%) 1/4 (25%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm progression 0/3 (0%) 1/4 (25%)
Nervous system disorders
Headache 0/3 (0%) 1/4 (25%)
Neuropathy peripheral 1/3 (33.3%) 0/4 (0%)
Restless legs syndrome 1/3 (33.3%) 0/4 (0%)
Psychiatric disorders
Hallucination 2/3 (66.7%) 0/4 (0%)
Mental status changes 1/3 (33.3%) 0/4 (0%)
Respiratory, thoracic and mediastinal disorders
Cough 1/3 (33.3%) 0/4 (0%)
Dyspnoea 1/3 (33.3%) 1/4 (25%)
Hypoxia 1/3 (33.3%) 0/4 (0%)
Nasal congestion 1/3 (33.3%) 0/4 (0%)
Oropharyngeal pain 1/3 (33.3%) 0/4 (0%)
Rales 1/3 (33.3%) 0/4 (0%)
Respiratory failure 0/3 (0%) 1/4 (25%)
Wheezing 1/3 (33.3%) 0/4 (0%)
Skin and subcutaneous tissue disorders
Eczema 1/3 (33.3%) 0/4 (0%)
Erythema 1/3 (33.3%) 0/4 (0%)
Hyperhidrosis 1/3 (33.3%) 1/4 (25%)
Petechiae 1/3 (33.3%) 0/4 (0%)
Purpura 1/3 (33.3%) 0/4 (0%)
Vascular disorders
Haematoma 0/3 (0%) 1/4 (25%)
Hypertension 1/3 (33.3%) 0/4 (0%)
Hypotension 0/3 (0%) 1/4 (25%)

Limitations/Caveats

The study was terminated prematurely due to strategic business reasons and was not due to any safety concerns.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

Results Point of Contact

Name/Title Pfizer ClinicalTrials.gov Call Center
Organization Pfizer, Inc.
Phone 1-800-718-1021
Email ClinicalTrials.gov_Inquiries@pfizer.com
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT02954653
Other Study ID Numbers:
  • B7861002
First Posted:
Nov 3, 2016
Last Update Posted:
Nov 21, 2019
Last Verified:
Nov 1, 2019