Phase I/II Trial of CPX-351 + Palbociclib in Patients With Acute Myeloid Leukemia

NCT03844997 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: CASE1918
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of Palbociclib in combination with investigational (experimental) drug, CPX-351 and evaluate the efficacy of Palbociclib in combination with chemotherapy as measured by overall response rate (ORR), i.e. complete response (CR) and CR with incomplete blood count recovery (CRi) by 2003 IWG criteria.

Conditions

Acute Myeloid Leukemia; AML

Outcome Measures

Primary Outcomes (2)

• Safety and Tolerability of Experimental Dose of Palbociclibin Combination With CPX-351 as Measured by Number of Participants With Dose Limiting Toxicities.

  If Grade 3-4 non-hematologic toxicity is observed in 1 or less of 6 patients treated, the dose of the study drug will be considered safe/tolerable. If Grade 3-4 non-hematologic toxicity is observed in 2 or more of 6 patients treated, 6 additional patients will be treated on the Phase IIa portion at a lower dose level (100 mg po).

  Between days 28-35 of starting treatment

• Efficacy of Palbociclibin Combination With Chemotherapy as Measured by Overall Response Rate (ORR).

  Efficacy of Palbociclibin combination with chemotherapy as measured by overall response rate (ORR) which is defined as complete response (CR) and CR with incomplete blood count recovery (CRi) by IWG criteria. Complete remission is defined as: Bone marrow blasts \<5%; absence ofcirculating blasts and blasts with Auerrods; absence of extramedullarydisease; absolute neutrophil count \>1.0x 109/L (1,000/μL); platelet count \>100 x109/L (100,000/μL) and CR with incomplete blood count recovery is defined as: All CR criteria except for residualneutropenia \[\<1.0 x 109/L (1,000/μL)\] orthrombocytopenia \[\<100 x 109/L(100,000/μL)\]. Either of these responses will constitute ORR.

  Up to 2 years from end of treatment, up to 27 months

Secondary Outcomes (4)

• Time to Response (TTR)

  Up to 2 years from end of treatment

• Duration of Response (DOR)

  Up to 2 years from end of treatment

• Event-free Survival (EFS)

  Up to 2 years from end of treatment

• Overall Survival (OS) Probability

  Up to 2 years from end of treatment, up to 27 months

Study Arms (1)

Palbociclib + CPX-351

EXPERIMENTAL

Palbociclib will be administered orally on day -1 and -2 at 125 mg PO during the phase IIaportion (dose level 0).Day 0 will be rest and then CPX-351 at 100 u/m2 will be started on days 1, 3, and 5 along with Palbociclib day 2, 4, and 6 followed by rest/monitoring period (day 7-28). If Grade 3-4 non-hematologic toxicity is observed in 1 or less of 6 patients treated, the study will move to Phase IIb. If Grade 3-4 non-hematologic toxicity is observed in 2 or more of 6 patients treated, 6 additional patients will be treated on the Phase IIa portion at a lower dose level (100 mg po) until a Phase IIb safe dose schedule is defined at which 1 or less out of 6 patients on the Phase IIa experience Grade 3-4 non-hematologic toxicity. After the Phase IIa portion ensures safety, the study will proceed with phase IIb. The phase IIb component is a Simon 2-stage design trial whose objective is to assess the clinical efficacy of the combination of Palbociclib and CPX-351.

Drug: Palcociclib; Drug: CPX-351

Interventions

Palcociclib DRUG

Palbociclib is an investigational (experimental) drug that works to induce early G1 arrest by inhibiting CDK4/6, which are two types of CDKs that are overexpressed in AML cell cancer lines. Palbociclib is experimental because it is not approved by the Food and Drug Administration (FDA). Palbociclib will be supplied as capsules or tablets containing 125 mg equivalents of Palbociclib free base

Also known as: IBRANCE

Palbociclib + CPX-351

CPX-351 DRUG

CPX-351 (daunorubicin and cytarabine) liposome for injection is a combination of daunorubicin and cytarabine in a 1:5 molar ratio encapsulated in liposomes for intravenous administration. CPX-351 is an investigational (experimental) drug that works as formulation of a fixed combination of the antineoplastic drugs cytarabine and daunorubicin. CPX-351 is experimental because it is not approved by the Food and Drug Administration (FDA).

Also known as: VYXEOS

Palbociclib + CPX-351

Eligibility Criteria

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

You may qualify if:

• Newly diagnosed acute myeloid leukemia according to 2016 WHO criteria(excluding APL \[AML-M3\]).
• Eastern Cooperative Oncology Group (ECOG) Performance Status \<2
• Subjects must have normal organ function as defined below:
• Total bilirubin \<2 times upper limit of normal ((≤ 3 x ULN if considered to be due to leukemic involvement or Gilbert's syndrome) or if higher than 2 times upper limit of normal with approval from the PI
• Serum Creatinine \<2 x ULNor if higher than 2 times upper limit of normal with approval from the PI
• Left ventricular ejection fraction of ≥45%
• Patients with secondary AML arising out of MDS (all subtypes under WHO classification), chronic myelomonocytic leukemia (CMML) and therapy-related AML are eligible.
• Women of childbearing potential should be advised to avoid becoming pregnant and men should be advised to not father a child while receiving treatment. All men and women of childbearing potential must use acceptable methods of birth control throughout the study
• Subjects must have the ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Prior treatment with CPX-351, Palbociclib or other cell cycle inhibitors.
• Any serious medical condition, laboratory abnormality, or psychiatric illness that, in the view of the treating physician, would place the participant at an unacceptable risk if he or she were to participate in the study or would prevent that person from giving informed consent.
• Any active malignancy (unrelated, non-hematological malignancy) diagnosed within the past 6 months of starting the study drug (other than curatively treated carcinoma-in-situ of the cervix or non-melanoma skin cancer).
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to CPX-351, Palbociclib or other cell cycle inhibitors.
• Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Known history of HIV or active hepatitis B or C.
• No major surgery within 2 weeks prior to study enrollment.
• Pregnancy or breast feeding
• Male and female patients who are fertile who do not agree to use an effective barrier methods of birth control (i.e. abstinence) to avoid pregnancy while receiving study treatment.
• Acute promyelocytic leukemia (APL)

Sponsors & Collaborators

• Sudipto Mukherjee, MD, PhD, MPH: lead

Study Sites (1)

Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

palbociclib; CPX-351

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Sudipto Mukherjee, MD, PhD
• Organization: Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

TaussigResearch@ccf.org

866-223-8100

Study Officials

• Sudipto Mukherjee, MD, PhD

  Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This is a single arm, open label study of the combination of Palbociclib with CPX-351 in adults with AML. The trial consists of two components: phase I to evaluate the safety with dose escalation of Palbociclib in combination with CPX-351 and phase II to evaluate the overall response rate of the combination in the targeted patient population. A cycle is 28 days.

Study Record Dates

• First Submitted: January 28, 2019
• First Posted: February 19, 2019
• Study Start: June 6, 2019
• Primary Completion: January 24, 2024
• Study Completion: January 24, 2024
• Last Updated: May 31, 2025
• Results First Posted: May 31, 2025

Record last verified: 2025-05

Locations

US (1)