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Recurrent Acute Lymphoblastic LeukemiaPhase 1NCT03132454

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

A Phase 1 study testing Decitabine, Dexamethasone and Palbociclib in people with Recurrent Acute Lymphoblastic Leukemia and Recurrent Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial 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). Read more about this study

Who is it for?
Ages 15 years and older
What is being tested?
Decitabine, Dexamethasone and Palbociclib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
1 siteUnited States
Study dates
25 Jul 2017to 31 Dec 2027
Phase
Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 15 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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)
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  • 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.

Who cannot join

  • 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,

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase I Study of Palbociclib Alone and in Combination in Patients With Relapsed and Refractory Leukemias

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DecitabineDrug

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

    Given IV

  • DexamethasoneDrug

    Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex

    Given IV or PO

  • PalbociclibDrug

    Also called 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

    Given PO

  • SorafenibDrug

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

    Given PO

Study groups in NCT03132454
Study groupRoleWhat they receive
Arm I (palbociclib, sorafenib)ExperimentalPatients 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.
Receives: Drug: Palbociclib; Drug: Sorafenib
Arm II (palbociclib, decitabine)ExperimentalPatients 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.
Receives: Drug: Decitabine; Drug: Palbociclib
Arm III (palbociclib, dexamethasone)ExperimentalPatients 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.
Receives: Drug: Dexamethasone; Drug: Palbociclib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to cycle 2 (each cycle is 28 days)

Secondary outcomes (4)

  1. 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.

    Measured: Up to 3 years

  2. 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.

    Measured: Up to 3 years

  3. 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.

    Measured: Up to 3 years

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

    Measured: Up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Apr 2017
  2. Study start25 Jul 2017
  3. Primary completion31 Dec 2027 (estimated)
  4. Study completion31 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03132454
Sponsor's protocol ID
2016-0772
Other IDs
NCI-2018-01194, 2016-0772
Status last verified
Oct 2026
First submitted
25 Apr 2017
Last updated
6 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

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