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

Primary Purpose

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

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Decitabine

Dexamethasone

Palbociclib

Sorafenib

About this trial

This is an interventional treatment trial for Recurrent Acute Lymphoblastic Leukemia

Eligibility Criteria

15 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

M D Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Arm I (palbociclib, sorafenib)

Arm II (palbociclib, decitabine)

Arm III (palbociclib, dexamethasone)

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Maximum tolerated dose (MTD) as determined by dose limiting toxicity (DLT)

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

Pharmacodynamic (PD) effects of palbociclib

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.

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)

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.

Assessment of biomarkers of response and resistance

The study will also explore the biomarkers associated with response or resistance to treatment using descriptive statistics and exploratory graphics.

Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

Full Information

NCT ID

NCT03132454

First Posted

April 25, 2017

Last Updated

September 6, 2023

Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT03132454

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

July 25, 2017 (Actual)

Primary Completion Date

December 31, 2023 (Anticipated)

Study Completion Date

December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

54 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm I (palbociclib, sorafenib)

Arm Type

Experimental

Arm Description

Arm Title

Arm II (palbociclib, decitabine)

Arm Type

Experimental

Arm Description

Arm Title

Arm III (palbociclib, dexamethasone)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Decitabine

Other Intervention Name(s)

5-Aza-2''-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Dexamethasone

Other Intervention Name(s)

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

Intervention Description

Given IV or PO

Intervention Type

Drug

Intervention Name(s)

Palbociclib

Other Intervention Name(s)

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

Intervention Description

Given PO

Intervention Type

Drug

Intervention Name(s)

Sorafenib

Other Intervention Name(s)

BA4 43 9006, BAY 43-9006, Bay-439006

Intervention Description

Given PO

Primary Outcome Measure Information:

Title

Maximum tolerated dose (MTD) as determined by dose limiting toxicity (DLT)

Description

Time Frame

Up to cycle 2 (each cycle is 28 days)

Secondary Outcome Measure Information:

Title

Pharmacodynamic (PD) effects of palbociclib

Description

Time Frame

Up to 3 years

Title

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.

Time Frame

Up to 3 years

Title

Assessment of biomarkers of response and resistance

Description

The study will also explore the biomarkers associated with response or resistance to treatment using descriptive statistics and exploratory graphics.

Time Frame

Up to 3 years

Title

Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

Time Frame

Up to 3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

15 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Tapan Kadia

Phone

713-563-3534

tkadia@mdanderson.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Tapan M Kadia

Organizational Affiliation

M.D. Anderson Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

M D Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Tapan M. Kadia

Phone

713-563-3534

First Name & Middle Initial & Last Name & Degree

Tapan M. Kadia

12. IPD Sharing Statement

Links:

URL

http://www.mdanderson.org

Description

University of Texas MD Anderson Cancer Center Website

Learn more about this trial

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

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