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

NCT03132454 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2016-0772NCI-2018-01194
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to cycle 2 (each cycle is 28 days)

Secondary Outcomes (4)

• Pharmacodynamic (PD) effects of palbociclib

  Up to 3 years

• 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)

  Up to 3 years

• Assessment of biomarkers of response and resistance

  Up to 3 years

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

  Up to 3 years

Study Arms (3)

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.

Drug: Palbociclib; Drug: 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.

Drug: Decitabine; Drug: 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.

Drug: Dexamethasone; Drug: Palbociclib

Interventions

Decitabine DRUG

Given IV

Also known as: 5-Aza-2''-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine

Arm II (palbociclib, decitabine)

Dexamethasone DRUG

Given IV or PO

Also known as: 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 DRUG

Given PO

Also known as: 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); Arm II (palbociclib, decitabine); Arm III (palbociclib, dexamethasone)

Sorafenib DRUG

Given PO

Also known as: BA4 43 9006, BAY 43-9006, Bay-439006

Arm I (palbociclib, sorafenib)

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants 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 participants with R/R ALL will be eligible for cohort C
• Age \>/= 15 years.
• Participants must not have had leukemia therapy for 14 days prior to starting palbociclib. However, participants with rapidly proliferative disease may receive hydroxyurea as needed until 24 hours prior to starting therapy on this protocol and starting the first cycle of study.
• Adequate organ function as defined below:
• liver function (bilirubin \< 2mg/dL, AST and/or ALT \<3 x ULN - or \<5 x ULN if related to leukemic involvement)
• kidney function (creatinine \< 1.5 x ULN ).
• known cardiac ejection fraction of \> or = 45% within the past 3 months
• 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.
• Participants must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the participants or his legally authorized representative is required prior to their enrollment on the protocol.

You may not qualify if:

• Participants 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 (NYHA Class III or IV), unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Participant with documented hypersensitivity to any of the components of the therapy program.
• Participants with active, uncontrolled 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.
• Participants with known history of serous retinopathy will not be eligible.
• Prior treatment with palbociclib,

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute

Interventions

Decitabine; Injections; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; palbociclib; Sorafenib

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Drug Administration Routes; Drug Therapy; Therapeutics; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phenylurea Compounds; Urea; Amides; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines

Study Officials

• Tapan M Kadia

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2017
• First Posted: April 27, 2017
• Study Start: July 25, 2017
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

US (1)