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Trial record 35 of 595 for:    Recruiting, Not yet recruiting, Available Studies | "Leukemia, Myeloid, Acute"

Pfizer Immunotherapy Combinations for Acute Myeloid Leukemia (AML) Multi-Arm Study 1

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ClinicalTrials.gov Identifier: NCT03390296
Recruitment Status : Recruiting
First Posted : January 4, 2018
Last Update Posted : August 17, 2018
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to learn about the safety and tolerability of 8 different drug combinations when given to patients with acute myeloid leukemia (AML). Researchers also want to learn if these drug combinations can help to control the disease.

The drug combinations being studied are:

  • PF-04518600 (OX40 agonist monoclonal antibody) alone
  • PF-04518600 and avelumab (anti-PDL1 mAb)
  • PF-04518600 and azacitidine
  • PF-04518600 and utomilumab (anti-41BB mAb)
  • avelumab and utomilumab
  • PF-04518600, avelumab, and azacitidine
  • gemtuzumab ozogamicin (anti-CD33 mAb) and glasdegib (smoothened inhibitor)
  • glasdegib and avelumab

This is an investigational study. Avelumab is FDA approved and commercially available for the treatment of advanced Merkel cell carcinoma and urothelial carcinoma. Azacitidine is FDA approved and commercially available for the treatment of myelodysplastic syndrome (MDS). Gemtuzumab ozogamicin is FDA approved and commercially approved for the treatment of AML. PF-04518600, utomilumab, and glasdegib are not FDA approved or commercially available.

It is considered investigational to use these drugs to treat AML. The study doctor can describe how the drugs are designed to work.

Up to 138 participants will be enrolled in this study. All will take part at MD Anderson.


Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: PF-04518600 Drug: Avelumab Drug: Azacitidine Drug: Utomilumab Drug: Gemtuzumab Ozogamicin Drug: Glasdegib Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 138 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label Phase IB/II Multi-Arm Study of OX40 Agonist Monoclonal Antibody (mAb), Anti-41BB mAb, Anti-PDL1 mAb, Smoothened Inhibitor, Anti-CD33 mAb, and Azacitidine as Single-Agents and/or Combinations for the Treatment of Patients With Acute Myeloid Leukemia (AML)
Actual Study Start Date : December 27, 2017
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2024


Arm Intervention/treatment
Experimental: Arm A: PF-04518600
Phase I Dose Escalation: PF-04518600 given on Days 1 and 14 of a 28 day cycle to identify the dose to be taken forward in the subsequent combination cohorts.
Drug: PF-04518600

Phase I Dose Escalation Starting Dose of PF-04518600: 0.3 given by vein on Days 1 and 14 of a 28 day cycle to identify the dose to be taken forward in the subsequent combination cohorts.

Phase II: Starting dose of PF-04518600 determined by Phase I given on Day 1 and 14 of a 28 day cycle.


Experimental: Arm B: PF-04518600 + Avelumab

Phase II: Starting dose of PF-04518600 determined by Phase I given on Day 1 and 14 of a 28 day cycle.

Avelumab given by vein on Days 1 and 14 of each 28-day cycle.

Drug: PF-04518600

Phase I Dose Escalation Starting Dose of PF-04518600: 0.3 given by vein on Days 1 and 14 of a 28 day cycle to identify the dose to be taken forward in the subsequent combination cohorts.

Phase II: Starting dose of PF-04518600 determined by Phase I given on Day 1 and 14 of a 28 day cycle.


Drug: Avelumab
Avelumab 10 mg/kg given by vein on Days 1 and 14 of each 28-day cycle.
Other Name: MSB0010718C

Experimental: Arm C: PF-04518600 + Azacitidine

Phase II: Starting dose of PF-04518600 determined by Phase I given on Day 1 and 14 of a 28 day cycle.

Azacitidine given either by vein or as an injection under the skin on Days 1-7 or Days 1-5 and 8-9 of each 28 day cycle.

Drug: PF-04518600

Phase I Dose Escalation Starting Dose of PF-04518600: 0.3 given by vein on Days 1 and 14 of a 28 day cycle to identify the dose to be taken forward in the subsequent combination cohorts.

Phase II: Starting dose of PF-04518600 determined by Phase I given on Day 1 and 14 of a 28 day cycle.


Drug: Azacitidine
Azacitidine 75 mg/m2 given either by vein or as an injection under the skin on Days 1-7 or Days 1-5 and 8-9 of each 28 day cycle.
Other Names:
  • 5-azacytidine
  • 5-aza
  • Vidaza
  • 5-AZC
  • AZA-CR
  • Ladakamycin
  • NSC-102816

Experimental: Arm D: PF-04518600 + Utomilumab

Phase II: Starting dose of PF-04518600 determined by Phase I given on Day 1 and 14 of a 28 day cycle.

Utomilumab given by vein on Days 1 and 14 of each 28 day cycle.

Drug: PF-04518600

Phase I Dose Escalation Starting Dose of PF-04518600: 0.3 given by vein on Days 1 and 14 of a 28 day cycle to identify the dose to be taken forward in the subsequent combination cohorts.

Phase II: Starting dose of PF-04518600 determined by Phase I given on Day 1 and 14 of a 28 day cycle.


Drug: Utomilumab
Utomilumab 100 mg given by vein on Days 1 and 14 of each 28 day cycle.
Other Names:
  • PF-05082566
  • Anti-CD137

Experimental: Arm E: Avelumab + Utomilumab

Avelumab given by vein on Days 1 and 14 of each 28 day cycle.

Utomilumab given by vein on Days 1 and 14 of each 28 day cycle.

Drug: Avelumab
Avelumab 10 mg/kg given by vein on Days 1 and 14 of each 28-day cycle.
Other Name: MSB0010718C

Drug: Utomilumab
Utomilumab 100 mg given by vein on Days 1 and 14 of each 28 day cycle.
Other Names:
  • PF-05082566
  • Anti-CD137

Experimental: Arm F: PF-04518600 + Azacitidine + Avelumab

Phase II: Starting dose of PF-04518600 determined by Phase I given on Day 1 and 14 of each 28 day cycle.

Azacitidine given either by vein or as an injection under the skin on Days 1-7 or Days 1-5 and 8-9 of each 28 day cycle.

Avelumab given by vein on Days 1 and 14 of each 28 day cycle.

Drug: PF-04518600

Phase I Dose Escalation Starting Dose of PF-04518600: 0.3 given by vein on Days 1 and 14 of a 28 day cycle to identify the dose to be taken forward in the subsequent combination cohorts.

Phase II: Starting dose of PF-04518600 determined by Phase I given on Day 1 and 14 of a 28 day cycle.


Drug: Avelumab
Avelumab 10 mg/kg given by vein on Days 1 and 14 of each 28-day cycle.
Other Name: MSB0010718C

Drug: Azacitidine
Azacitidine 75 mg/m2 given either by vein or as an injection under the skin on Days 1-7 or Days 1-5 and 8-9 of each 28 day cycle.
Other Names:
  • 5-azacytidine
  • 5-aza
  • Vidaza
  • 5-AZC
  • AZA-CR
  • Ladakamycin
  • NSC-102816

Experimental: Arm G: Gemtuzumab Ozogamycin (GO) + Glasdegib

Gemtuzumab ozogamicin given by vein on Days 1, 4, and 7 of each 28 day cycle.

Glasdegib tablets taken by mouth every morning of each 28 day cycle.

Drug: Gemtuzumab Ozogamicin
Gemtuzumab Ozogamicin 3 mg/m^2 given by vein on Days 1, 4, and 7 of each 28 day cycle.
Other Names:
  • Gemtuzumab
  • Mylotarg

Drug: Glasdegib
Glasdegib 100 mg tablets taken by mouth every morning of each 28 day cycle.
Other Name: PF-04449913

Experimental: Arm H: Glasdegib + Avelumab

Glasdegib tablets taken by mouth every morning of each 28 day cycle.

Avelumab given by vein on Days 1 and 14 of each 28 day cycle.

Drug: Avelumab
Avelumab 10 mg/kg given by vein on Days 1 and 14 of each 28-day cycle.
Other Name: MSB0010718C

Drug: Glasdegib
Glasdegib 100 mg tablets taken by mouth every morning of each 28 day cycle.
Other Name: PF-04449913




Primary Outcome Measures :
  1. Adverse Events of Multiple Combination Regimens of PF04518600, Avelumab, Utomilumab, Azacitidine, Gemtuzumab Ozogamycin, and Glasdegib) in Patients with Relapsed/Refractory (RR) AML [ Time Frame: 28 days ]
    Adverse events determined by the NCI-CTCAE criteria specific for leukemia,

  2. Composite Complete Response (CRc) of Arms B-G [ Time Frame: 3 months ]

    (CRc) defined as CR + complete response with incomplete recovery of platelets (CRp) + complete response with incomplete recovery of counts (CRi).

    Response assessed by the International Working Group for AML.



Secondary Outcome Measures :
  1. Morphologic Leukemia Free Survival (MLFS) in Arms A - G [ Time Frame: Day 28 of Cycles 1, 2, 4 and 8 ]
    Response assessed by the International Working Group for AML.

  2. Partial Response (PR) in Arms A - G [ Time Frame: Day 28 of Cycles 1, 2, 4 and 8 ]
    Response assessed by the International Working Group for AML.

  3. Hematologic Improvement (HI) Rate in Arms A - G [ Time Frame: Day 28 of Cycles 1, 2, 4 and 8 ]
    Response assessed by the International Working Group for AML.

  4. Relapse Free Survival (RFS) in Arms A - G [ Time Frame: Day 28 of Cycles 1, 2, 4 and 8 ]
    Response assessed by the International Working Group for AML.

  5. Time to Next Therapy (TNT) in Arms A - G [ Time Frame: Day 28 of Cycles 1, 2, 4 and 8 ]
    Response assessed by the International Working Group for AML.

  6. Mortality in Arms A - G [ Time Frame: 4 and 8 weeks ]
  7. Overall Survival (OS) in Arms A - G [ Time Frame: 5 years ]
  8. minimal residual disease (MRD) in Arms A - H [ Time Frame: 1 month ]
    Minimal residual disease (MRD) determined by multiparametric flow-cytometry.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Arms A - G: RR AML: Patients with AML who are refractory or relapsed (any salvage) with no available therapies or not candidates for available therapies. For patients with prior MDS or chronic myelomonocytic leukemia (CMML) or MPN who transformed to AML, therapy received for MDS, CMML, or MPN is NOT considered as prior therapy for AML.
  2. Prior therapy with hydroxyurea, chemotherapy, biological or targeted therapy (e.g. FLT3 inhibitors, other kinase inhibitors), or hematopoietic growth factors is permitted in all arms of the study.
  3. Age >/=18 years
  4. Eastern Cooperative Oncology Group (ECOG) Performance Status </=2
  5. Adequate hepatic (serum direct bilirubin </= 1.5 x upper limit normal (ULN) (or </= 3.0 x ULN if deemed to be elevated due to leukemia), alanine aminotransferase and/or aspartate transaminase </= 2.5 x ULN (or </= 5.0 x ULN if deemed elevated due to leukemia). Note: Subjects with Gilbert's Syndrome may have a bilirubin > 1.5 × ULN .
  6. Adequate renal function defined by an estimated creatinine clearance >/= 40 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)
  7. Patients must provide written informed consent.
  8. In the absence of rapidly progressive disease, the interval from prior treatment to the time of initiation of protocol therapy will be at least 14 days for prior anti-leukemic therapy, with the exception of hydrea as noted below, OR at least 5 half-lives for cytotoxic/noncytotoxic agents, whichever is shorter. The half-life for the therapy in question will be based on published pharmacokinetic literature (abstracts, manuscripts, investigator brochure's, or drug-administration manuals) and will be documented in the protocol eligibility document. The toxicity from prior therapy should have resolved to Grade </=1, however alopecia and sensory neuropathy Grade </=2 not constituting a safety risk based on investigators judgement is acceptable. Since the effect of most IO-agents, HMA-therapies, SMO-inhibitors may be delayed, use of hydroxyurea for patients with rapidly proliferative disease is allowed before the start of study therapy and will not require a washout.
  9. Concurrent therapy for CNS prophylaxis or continuation of therapy for controlled CNS disease is permitted. Patients with a known history of CNS disease or leukemic brain metastasis must have been treated locally, have at least 3 consecutive LPs with no evidence of CNS leukemia, and must be clinically stable for at least 4 weeks prior to enrollment and have no ongoing neurological symptoms that in the opinion of the treating physician are related to the CNS disease (sequelae that are a consequence of the treatment of the CNS disease are acceptable).
  10. Females must be surgically or biologically sterile or postmenopausal (amenorrheic for at least 12 months) or if of childbearing potential, must have a negative serum or urine pregnancy test within 72 hours before the start of the treatment.
  11. Women of childbearing potential must agree to use an adequate method of contraception during the study and until 3 months after the last treatment. Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 3 months after the last treatment. Adequate methods of contraception include: • Total abstinence when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
  12. Continued from No. 11; • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment • Male sterilization (at least 6 months prior to screening). For female patients on the study, the vasectomized male partner should be the sole partner for that patient
  13. Continued from No. 12; • Combination of any of the two following (a+b or a+c or b+c) a. Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception b. Placement of an intrauterine device (IUD) or intrauterine system (IUS) c. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository In case of use of oral contraception, women should have been stable on the same pill before taking study treatment.
  14. Continued from No. 13; Note: Oral contraceptives are allowed but should be used in conjunction with a barrier method of contraception due to unknown effect of drug-drug interaction. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.

Exclusion Criteria:

  1. Patients with a known allergy or hypersensitivity to the protocol therapies or any of their components to be used in the arm the patient is to be enrolled on. Known severe hypersensitivity reactions to monoclonal antibodies (Grade >/= 3 NCI CTCAE v 4.03), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma).
  2. Patients with a known history of severe interstitial lung disease or severe pneumonitis or active pneumonitis/pneumonia or pulmonary pathology that is not well controlled in the opinion of the treating physician and/or PI.
  3. Patients who have previously been treated with any of the agents or same class of agents they are scheduled to receive will be excluded. For example, a patient previously treated with a PD1 or PDL1-based therapy will not be eligible for avelumab+4-1BB or avelumab+OX40 arms. A patient previously treated with an OX40 based therapy will not be eligible for any of the OX40 single-agent or combination arms.
  4. Clinically significant (i.e., active) cardiovascular disease: acute cerebral vascular accident/stroke (< 6 months prior to enrollment) excluding TIA, myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (>/= New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
  5. Ejection fraction < 50% on screening ECHO or MUGA
  6. Persisting toxicity related to prior therapy of Grade >1 NCI-CTCAE v 4.03; however, alopecia and sensory neuropathy Grade </= 2 is acceptable
  7. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent: a. Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible b. Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses </=10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
  8. Prior organ transplantation including allogenic stem-cell transplantation within 3 months prior to planned enrollment.
  9. Patients with symptomatic CNS leukemia or patients with poorly controlled CNS leukemia.
  10. Active and uncontrolled disease (active infection requiring systemic therapy, fever likely secondary to infection within prior 48 hours, uncontrolled hypertension despite adequate medical therapy as judged by the treating physician.
  11. Known history of testing positive for HIV or known acquired immunodeficiency syndrome
  12. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive
  13. Vaccination within 4 weeks of the first dose of avelumab and while on trials is prohibited except for administration of inactivated vaccines
  14. Other severe acute or chronic medical conditions that is active and not well controlled including colitis, inflammatory bowel disease, or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
  15. Patients unwilling or unable to comply with the protocol.
  16. Pregnant or breastfeeding
  17. Known alcohol or drug abuse within the last 1 year
  18. Acute promyelocytic leukemia (APL).
  19. Cardiac exclusions specific to Glasdegib and OX40 containing arms: Any one of the following ongoing or in the previous 6 months: congenital long QT syndrome, Torsades de pointes or any clinically significant ventricular fibrillation, sustained ventricular tachyarrhythmia requiring medical intervention, right bundle branch block + left anterior hemiblock (i.e. bifascicular block): isolated RBBB without a bifascicular block will not be an exclusion criterion; complete left bundle branch block, unstable angina or myocardial infarction, coronary/peripheral artery bypass graft, CVA, transient ischemic attack or symptomatic pulmonary emboli, as well as bradycardia defined as <50 bpms on screening or Day 1 EKG. Known history of second or third degree heart block (may be eligible if the patient currently has a pacemaker). Active cardiac dysrhythmias of NCI CTCAE grade >/= 2 (eg, atrial fibrillation) or QTc interval > 470 msec within 4 weeks prior to starting the study drug.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03390296


Contacts
Contact: Naval Daver, MD 713-794-4392 ndaver@mdanderson.org

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact       ndaver@mdanderson.org   
Sponsors and Collaborators
M.D. Anderson Cancer Center
Pfizer
Investigators
Principal Investigator: Naval Daver, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03390296     History of Changes
Other Study ID Numbers: 2017-0337
NCI-2018-00972 ( Registry Identifier: NCI CTRP )
First Posted: January 4, 2018    Key Record Dates
Last Update Posted: August 17, 2018
Last Verified: August 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Acute Myeloid Leukemia
AML
Relapsed/refractory
RR
PF-04518600
Avelumab
MSB0010718C
Azacitidine
5-azacytidine
5-AZA
Vidaza
5-AZC
AZA-CR
Ladakamycin
NSC-102816
Azacytidine
Utomilumab
PF-05082566
Anti-CD137
Gemtuzumab ozogamicin
Gemtuzumab
Mylotarg
Glasdegib
PF-04449913

Additional relevant MeSH terms:
Leukemia, Myeloid, Acute
Leukemia
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Azacitidine
Gemtuzumab
Antibodies, Monoclonal
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Physiological Effects of Drugs