Clinical Trial: NCT03132454 - My Cancer Genome

NCT03132454

Description:

This phase I trial studies the side effects and best dose of palbociclib when given alone and in combination with sorafenib, decitabine, or dexamethasone in treating patients with leukemia that has come back (recurrent) or that does not respond to previous treatment (refractory). Palbociclib, sorafenib, and decitabine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving palbociclib alone and in combination with sorafenib, decitabine, or dexamethasone may work better in treating patients with recurrent or refractory leukemia.

Related Conditions:

Acute Lymphoblastic Leukemia
Acute Myeloid Leukemia

Recruiting Status:

Recruiting

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT03132454

Trial Eligibility

Document

Title

Brief Title: Palbociclib and Sorafenib, Decitabine, or Dexamethasone in Treating Patients With Recurrent or Refractory Leukemia
Official Title: Phase I Study of Palbociclib Alone and in Combination in Patients With Relapsed and Refractory Leukemias

Clinical Trial IDs

ORG STUDY ID: 2016-0772
SECONDARY ID: NCI-2018-01194
SECONDARY ID: 2016-0772
SECONDARY ID: P30CA016672
NCT ID: NCT03132454

Conditions

Recurrent Acute Lymphoblastic Leukemia
Recurrent Acute Myeloid Leukemia
Refractory Acute Lymphoblastic Leukemia
Refractory Acute Myeloid Leukemia

Interventions

Drug	Synonyms	Arms
Decitabine	5-Aza-2''-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine	Arm II (palbociclib, decitabine)
Dexamethasone	Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex	Arm III (palbociclib, dexamethasone)
Palbociclib	6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one, Ibrance, PD 0332991, PD 332991, PD 991, PD-0332991	Arm I (palbociclib, sorafenib)
Sorafenib	BA4 43 9006, BAY 43-9006, Bay-439006	Arm I (palbociclib, sorafenib)

Purpose

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of
      various combinations with palbociclib in patients with relapsed and refractory leukemias.

      SECONDARY OBJECTIVES:

      I. To assess pharmacodynamic effects of palbociclib on the Cyclin-CDK-Rb axis in leukemic
      blasts of patients with relapsed/refractory (R/R) leukemias.

      II. To explore the efficacy (complete response [CR], complete remission without platelet
      recovery [CRp], complete remission without blood count recovery [CRi], partial response [PR],
      or clinical benefit [CB]) of palbociclib as a single-agent and in combinations in patients
      with R/R leukemias.

      III. To explore biomarkers of response and resistance in patients with R/R leukemias treated
      with palbociclib.

      IV. To assess the safety and tolerability of one cycle of single-agent palbociclib in
      patients with R/R leukemias.

      OUTLINE: This is a dose-escalation study of sorafenib, decitabine, and dexamethasone.
      Patients are assigned to 1 of 3 arms.

      ARM I: Patients receive palbociclib orally (PO) once daily (QD) on days 1-28. Patients also
      receive sorafenib PO QD on days 1-28 beginning on cycle 2. Treatment repeats every 28 days
      for up to 8 cycles in the absence of disease progression or unacceptable toxicity.

      ARM II: Patients receive palbociclib as in Arm I. Beginning cycle 2, patients receive
      palbociclib PO QC on days 1-7 and decitabine intravenously (IV) QD over 1 hour on days 8-17
      of cycle 2 and days 8-12 of cycles 3-8. Treatment repeats every 28 days for up to 8 cycles in
      the absence of disease progression or unacceptable toxicity.

      ARM III: Patients receive palbociclib as in Arm I. Patients also receive dexamethasone PO QD
      or IV over 15-30 minutes on days 1-4 and 15-18 beginning on cycle 2. Treatment repeats every
      28 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up periodically.

Trial Arms

Name	Type	Description	Interventions
Arm I (palbociclib, sorafenib)	Experimental	Patients receive palbociclib PO QD on days 1-28. Patients also receive sorafenib PO QD on days 1-28 beginning on cycle 2. Treatment repeats every 28 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.	Palbociclib Sorafenib
Arm II (palbociclib, decitabine)	Experimental	Patients receive palbociclib as in Arm I. Beginning cycle 2, patients receive palbociclib PO QC on days 1-7 and decitabine IV QD over 1 hour on days 8-17 of cycle 2 and days 8-12 of cycles 3-8. Treatment repeats every 28 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.	Decitabine Palbociclib
Arm III (palbociclib, dexamethasone)	Experimental	Patients receive palbociclib as in Arm I. Patients also receive dexamethasone PO QD or IV over 15-30 minutes on days 1-4 and 15-18 beginning on cycle 2. Treatment repeats every 28 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.	Dexamethasone Palbociclib

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with a diagnosis of histologically confirmed relapsed or refractory (R/R)
             acute myeloid leukemia or R/R acute lymphoblastic leukemia for which no available
             standard therapies are indicated or anticipated to result in a durable response

          -  Only patients with R/R ALL will be eligible for cohort C

          -  Patients must not have had leukemia therapy for 14 days prior to starting palbociclib.
             However, patients with rapidly proliferative disease may receive hydroxyurea as needed
             until 24 hours prior to starting therapy on this protocol and during the first cycle
             of study

          -  Bilirubin =< 2 mg/dL

          -  Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 3 x upper
             limit of normal (ULN) or =< 5 x ULN if related to leukemic involvement

          -  Creatinine =< 1.5 x ULN

          -  Known cardiac ejection fraction of > or = 45% within the past 3 months

          -  Eastern Cooperative Oncology Group (ECOG) performance status of =< 2

          -  A negative urine pregnancy test is required within 1 week for all women of
             childbearing potential prior to enrolling on this trial

          -  Patient must have the ability to understand the requirements of the study and signed
             informed consent. A signed informed consent by the patient or his legally authorized
             representative is required prior to their enrollment on the protocol

        Exclusion Criteria:

          -  Pregnant women are excluded from this study because the agent used in this study has
             the potential for teratogenic or abortifacient effects. Because there is a potential
             risk for adverse events in nursing infants secondary to treatment of the mother with
             the chemotherapy agents, breastfeeding should also be avoided

          -  Uncontrolled intercurrent illness including, but not limited to active uncontrolled
             infection, symptomatic congestive heart failure (New York Heart Association [NYHA]
             class III or IV), unstable angina pectoris, clinically significant cardiac arrhythmia,
             or psychiatric illness/social situations that would limit compliance with study
             requirements

          -  Patient with documented hypersensitivity to any of the components of the therapy
             program

          -  Patients with active, uncontrolled central nervous system (CNS) leukemia will not be
             eligible

          -  Men and women of childbearing potential who do not practice contraception. Women of
             childbearing potential and men must agree to use contraception prior to study entry
             and for the duration of study participation

          -  Patients with known history of serous retinopathy will not be eligible

          -  Prior treatment with palbociclib

Maximum Eligible Age:	N/A
Minimum Eligible Age:	15 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Maximum tolerated dose (MTD) as determined by dose limiting toxicity (DLT)
Time Frame:	Up to cycle 2 (each cycle is 28 days)
Safety Issue:
Description:	MTD is defined as the highest dose level in which 6 patients have been treated with at most 1 instance of dose limiting toxicity using a classic '3+3' dose-escalation design. DLT is defined as drug-related adverse events during cycle two (i.e., the first cycle of palbociclib in combination). The number and proportion of DLTs will be summarized by treatment arm and dose level.

Secondary Outcome Measures

Measure:	Pharmacodynamic (PD) effects of palbociclib
Time Frame:	Up to 3 years
Safety Issue:
Description:	PD biomarker concentration will be summarized by time points. The relationship between drug concentrations and PD effects will be explored graphically. Based on review of these graphs, analyses to describe the relationship may also be performed.

Measure:	Efficacy as determined by complete response (CR]), complete remission without platelet recovery (CRp), complete remission without blood count recovery (CRi), partial response (PR), or clinical benefit (CB)
Time Frame:	Up to 3 years
Safety Issue:
Description:	For the preliminary efficacy analysis, the study will summarize the number and rate of CR, CRp, CRi and PR by treatment arm and dose level.

Measure:	Assessment of biomarkers of response and resistance
Time Frame:	Up to 3 years
Safety Issue:
Description:	The study will also explore the biomarkers associated with response or resistance to treatment using descriptive statistics and exploratory graphics.

Measure:	Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time Frame:	Up to 3 years
Safety Issue:
Description:

Details

Phase:	Phase 1
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	M.D. Anderson Cancer Center

Last Updated

December 21, 2020

Clinical Trials /

Palbociclib and Sorafenib, Decitabine, or Dexamethasone in Treating Patients With Recurrent or Refractory Leukemia