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

NCT02954653 | Terminated Phase 1 Results

• 1 other identifier: B7861002
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 4

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.

Conditions

Acute Myeloid Leukemia

Keywords

relapsed; refractory; acute myeloid leukemia; AML

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Dose-Limiting Toxicities (DLTs) [Part 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.

  Day 1 to Day 28 of Cycle 1

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

  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.

  1 year

• Number of Participants With Laboratory Abnormalities [Part 2]

  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).

  1 year

• Objective Response Rate (ORR) - Percentage of Participants With Objective Response [Part 2]

  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.

  16 weeks

• Duration of Objective Response Rate (ORR) [Part 2]

  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.

  16 weeks

• Progression Free Survival [Part 2]

  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).

  16 weeks

Secondary Outcomes (25)

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

  1 year

• 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

• 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

• 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

• Objective Response Rate (ORR) - Percentage of Participants With Objective Response [Part 1]

  16 weeks

Study Arms (4)

Dose Escalation

EXPERIMENTAL

Single agent PF-06747143 dose escalation

Biological: PF-06747143

Cohort 1

ACTIVE COMPARATOR

PF-06747143 with standard dose cytarabine and daunorubicin.

Biological: PF-06747143; Drug: Cytarabine; Drug: Daunorubicin

Cohort 2

ACTIVE COMPARATOR

PF-06747143 in combination with Azacitidine or Decitabine.

Biological: PF-06747143; Drug: Azacitidine; Drug: Decitabine

Cohort 3

EXPERIMENTAL

PF-06747143 dose expansion as a single agent.

Biological: PF-06747143

Interventions

PF-06747143 BIOLOGICAL

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

Cohort 1; Cohort 2; Cohort 3; Dose Escalation

Cytarabine DRUG

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

Cohort 1

Daunorubicin DRUG

60-90 mg/m2 daily for 3 days

Cohort 1

Azacitidine DRUG

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

Cohort 2

Decitabine DRUG

20 mg/m2 continuous intravenous infusion for 5 days in a 4-week schedule

Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Pfizer: lead

Study Sites (4)

The University of Arizona Cancer Center-North Campus

Tucson, Arizona, 85719, United States

Location

Banner-University Medical Center Tucson

Tucson, Arizona, 85724, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

Related Publications (1)

• Liu SH, Gu Y, Pascual B, Yan Z, Hallin M, Zhang C, Fan C, Wang W, Lam J, Spilker ME, Yafawi R, Blasi E, Simmons B, Huser N, Ho WH, Lindquist K, Tran TT, Kudaravalli J, Ma JT, Jimenez G, Barman I, Brown C, Chin SM, Costa MJ, Shelton D, Smeal T, Fantin VR, Pernasetti F. A novel CXCR4 antagonist IgG1 antibody (PF-06747143) for the treatment of hematologic malignancies. Blood Adv. 2017 Jun 21;1(15):1088-1100. doi: 10.1182/bloodadvances.2016003921. eCollection 2017 Jun 27.

  PMID: 29296751 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence

Interventions

Cytarabine; Daunorubicin; Azacitidine; Decitabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Aza Compounds; Ribonucleosides

Limitations and Caveats

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

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2016
• First Posted: November 3, 2016
• Study Start: November 28, 2016
• Primary Completion: December 5, 2017
• Study Completion: December 5, 2017
• Last Updated: November 21, 2019
• Results First Posted: March 18, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)