Pomalidomide + Chemotherapy for Acute Myeloid Leukemia

Not currently recruiting at 11 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Strong CYP1A2 inhibitors

Disqualifiers: Wilson's disease, CNS leukemia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding pomalidomide to regular chemotherapy can improve treatment for people with acute myeloid leukemia (AML) that has specific myelodysplastic (blood cell-related) changes. Pomalidomide may help by stopping blood vessel growth, boosting the immune system, and killing cancer cells. Participants will receive either the standard chemotherapy drugs (liposome-encapsulated daunorubicin-cytarabine, also known as CPX-351 or Vyxeos) alone or with pomalidomide to determine which is more effective. The trial seeks individuals recently diagnosed with AML linked to previous blood disorders like myelodysplastic syndrome who have not yet received treatment for AML. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in AML treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that anti-cancer therapy should be stopped more than 72 hours before starting the trial treatment, and the use of strong CYP1A2 inhibitors should be avoided. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that pomalidomide is usually well-tolerated when combined with other treatments for leukemia. In studies, patients with acute leukemia generally handled pomalidomide well, with no major safety issues reported. However, rare cases of acute myelogenous leukemia (AML) have occurred in patients using pomalidomide, though these cases were not specific to myeloma patients.

For liposome-encapsulated daunorubicin-cytarabine, research indicates it can be an effective treatment with a good safety record. Patients often live longer compared to those receiving traditional chemotherapy. This special form of the drugs maintains a steady level of medication in the body, which can lead to better results and fewer side effects.

Both treatments have been thoroughly studied, and evidence suggests they are generally safe for patients with acute leukemia. However, like any treatment, risks exist, and discussing these with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatment because it combines a novel liposome-encapsulated form of the chemotherapy drugs daunorubicin and cytarabine with pomalidomide. This liposome-encapsulation allows for more targeted delivery of the chemotherapy, potentially reducing side effects and increasing the drugs' effectiveness against Acute Myeloid Leukemia (AML). Additionally, pomalidomide is an immunomodulatory agent that can enhance the immune system's ability to fight cancer cells, offering a new mechanism of action compared to traditional chemotherapy. This combination aims to improve patient outcomes and provide a more efficient, targeted approach to treating AML.

What evidence suggests that this trial's treatments could be effective for acute leukemia with myelodysplastic syndrome-related changes?

Research has shown that a treatment using liposome-encapsulated daunorubicin and cytarabine is effective for acute myeloid leukemia (AML). Studies have found that it helps patients, particularly older ones, live longer than traditional chemotherapy and increases the likelihood of reaching a stage where they can receive a potentially curative stem cell transplant. In this trial, some participants will receive this treatment alone.

Others will receive a combination of liposome-encapsulated daunorubicin and cytarabine with pomalidomide. Pomalidomide shows promise because it boosts the immune system and helps kill cancer cells. In previous studies, many patients taking pomalidomide achieved complete remission and experienced a good survival period. Combining pomalidomide with chemotherapy might enhance effectiveness by attacking the cancer in different ways. ^{2 3 4 6 7}

Who Is on the Research Team?

Joshua F Zeidner

Principal Investigator

Ohio State University Comprehensive Cancer Center LAO

Are You a Good Fit for This Trial?

Adults aged 18-75 with newly diagnosed acute myeloid leukemia (AML) and specific genetic mutations or changes related to myelodysplastic syndrome, who have good organ function and performance status. They must not have had previous AML treatment except hydroxyurea or leukapheresis, no Wilson's Disease, uncontrolled illnesses, prior allogeneic stem cell transplant, or certain cumulative doses of daunorubicin. Women of childbearing potential must test negative for pregnancy and use two forms of birth control.

Inclusion Criteria

Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 x institutional ULN

My leukemia is classified as therapy-related or stems from a previous blood disorder.

My leukemia diagnosis was confirmed with a specific test showing more than 20% immature blood cells.

Exclusion Criteria

Patients with psychiatric illness/social situations that would limit compliance with study requirements

My white blood cell count is high, but it can be lowered for treatment.

Patients who are receiving any other investigational agents

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3, and 5. In Arm A, pomalidomide is added orally once daily for 14 days starting between days 21-30.

Approximately 4-6 weeks

Consolidation

Patients who achieve CR/CRi receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3. Treatment repeats every 21 days for 2 cycles.

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up for 30 days, then up to 5 years.

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Liposome-encapsulated Daunorubicin-Cytarabine
• Pomalidomide

Trial Overview The trial is testing the addition of Pomalidomide—an immunomodulatory drug—to standard chemotherapy (Daunorubicin and Cytarabine Liposome) in patients with AML that has characteristics similar to myelodysplastic syndrome. The study aims to see if this combination improves outcomes compared to the usual treatment alone.

How Is the Trial Designed?

Group I: Arm A (daunorubicin and cytarabine liposome, pomalidomide) Experimental Treatment 4 Interventions

INDUCTION: Patients receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3, and 5 and then pomalidomide PO QD beginning between days 21-30 for 14 days in the absence of disease progression or unacceptable toxicity. Patients who do not respond, may receive a second cycle of liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3 in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients who achieve CR/CRi receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3. Treatment repeats every 21 days for 2 cycles in the absence of disease progression and unacceptable toxicity. Patients also undergo bone marrow aspirate and biopsy and collection of blood samples throughout all phases of the trial.

Group II: Arm B (daunorubicin and cytarabine liposome) Active Control 3 Interventions

INDUCTION: Patients receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3, and 5 in the absence of disease progression or unacceptable toxicity. Patients who do not respond, may receive a second cycle of liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3 in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients who achieve CR/CRi receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3. Treatment repeats every 21 days for 2 cycles in the absence of disease progression and unacceptable toxicity. Patients also undergo bone marrow aspirate and biopsy and collection of blood samples throughout all phases of the trial.

Liposome-encapsulated Daunorubicin-Cytarabine is already approved in United States for the following indications:

Approved in United States as Vyxeos for:

• Acute Myeloid Leukemia with myelodysplasia-related changes (AML-MRC)
• Therapy-related AML (t-AML)

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase 3 study involving 309 patients aged 60 to 75 with high-risk acute myeloid leukemia, CPX-351 significantly improved median overall survival compared to conventional 7+3 chemotherapy, while maintaining a similar safety profile.

The Quality-adjusted Time Without Symptoms of disease or Toxicity (Q-TWiST) analysis showed that CPX-351 provided a relative gain of 53.6% in quality-adjusted survival compared to 7+3, indicating a substantial clinical benefit for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality-adjusted Time Without Symptoms of disease or Toxicity (Q-TWiST) analysis of CPX-351 versus 7 + 3 in older adults with newly diagnosed high-risk/secondary AML. Cortes, JE., Lin, TL., Uy, GL., et al.[2021]

Vyxeos (CPX-351) received FDA approval for treating adults with newly diagnosed therapy-related acute myeloid leukemia (t-AML) or acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), based on a study involving 309 patients aged 60-75 that showed improved overall survival (9.6 months vs. 5.9 months with standard treatment).

The safety profile of Vyxeos was comparable to the standard treatment, but it was associated with longer periods of neutropenia and thrombocytopenia, highlighting the need for careful monitoring and a warning against switching between different formulations of daunorubicin and cytarabine during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: (Daunorubicin and Cytarabine) Liposome for Injection for the Treatment of Adults with High-Risk Acute Myeloid Leukemia. Krauss, AC., Gao, X., Li, L., et al.[2020]

CPX-351 (Vyxeos®) is a dual-drug liposomal formulation of cytarabine and daunorubicin designed to improve efficacy in treating acute myeloid leukemia (AML) by maintaining a synergistic 5:1 drug ratio, which enhances its effectiveness compared to traditional chemotherapy regimens.

The liposomal encapsulation allows for controlled release and preferential uptake by malignant cells, which helps to protect the drugs from metabolism and reduces exposure to off-target tissues, contributing to a favorable safety profile while effectively targeting leukemia cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CPX-351: a nanoscale liposomal co-formulation of daunorubicin and cytarabine with unique biodistribution and tumor cell uptake properties. Mayer, LD., Tardi, P., Louie, AC.[2020]

CPX-351, a liposomal formulation of cytarabine and daunorubicin, shows improved safety and efficacy in treating acute myeloid leukemia by providing prolonged tissue exposure and altered distribution compared to traditional non-liposomal combinations.

Preclinical studies indicate that CPX-351 maintains similar drug release and metabolism patterns as the standard treatment but results in lower unbound plasma concentrations, which may contribute to its enhanced therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, drug metabolism, and tissue distribution of CPX-351 in animals. Wang, Q., Tardi, P., Sadowski, N., et al.[2021]

In a phase II study involving 125 patients with acute myeloid leukemia (AML) in first relapse, CPX-351 showed improved response rates and lower 60-day mortality in patients classified as poor-risk according to the European Prognostic Index.

While CPX-351 did not meet the overall statistical criteria for 1-year survival improvement compared to standard salvage chemotherapy, it demonstrated significant benefits in event-free survival and overall survival for the poor-risk subgroup, suggesting it may be a more effective treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II, multicenter, randomized trial of CPX-351 (cytarabine:daunorubicin) liposome injection versus intensive salvage therapy in adults with first relapse AML. Cortes, JE., Goldberg, SL., Feldman, EJ., et al.[2021]

In a study involving 53 AML patients, CPX-351 demonstrated significant cytotoxic activity, particularly in cases with the FLT3-ITD mutation, which were five times more sensitive to the treatment.

The effectiveness of CPX-351 was consistent across various leukemia types, with its cellular uptake correlating with its cytotoxic potency, suggesting that ex vivo testing could help identify AML patients who would benefit most from this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CPX-351 exhibits potent and direct ex vivo cytotoxicity against AML blasts with enhanced efficacy for cells harboring the FLT3-ITD mutation. Gordon, MJ., Tardi, P., Loriaux, MM., et al.[2018]

CPX-351, a liposomal formulation of cytarabine and daunorubicin, showed high efficacy in treating childhood acute lymphoblastic leukemia (ALL) xenograft models, achieving complete responses in four B-lineage models and a partial response in one T-lineage model.

The drug was administered at a dose that resulted in plasma drug exposures similar to those seen in patients with acute myeloid leukemia (AML), indicating its potential effectiveness and safety for use in pediatric leukemia treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of CPX-351, (cytarabine:daunorubicin) liposome injection, against acute lymphoblastic leukemia (ALL) xenograft models of the Pediatric Preclinical Testing Program. Carol, H., Fan, MM., Harasym, TO., et al.[2021]

VYXEOS™, a liposomal formulation of daunorubicin and cytarabine, has been shown to significantly improve overall survival and event-free survival in older patients with newly diagnosed high-risk acute myeloid leukaemia (AML) compared to conventional chemotherapy (7+3).

The treatment also resulted in higher rates of complete remission and was well-tolerated, with a safety profile similar to that of the standard chemotherapy regimen, making it a valuable option for patients with therapy-related AML or AML with myelodysplasia-related changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daunorubicin/Cytarabine Liposome: A Review in Acute Myeloid Leukaemia. Blair, HA.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12185649/

The Role of CPX-351 in the Acute Myeloid Leukemia ... These protective effects and confirmed effectiveness in everyday practice mean CPX-351 is a safe and effective treatment option for people with ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2017.77.6112

CPX-351 (cytarabine and daunorubicin) Liposome for ... CPX-351 treatment is associated with significantly longer survival compared with conventional 7+3 in older adults with newly diagnosed sAML.

3. ashpublications.org ashpublications.org/blood/article/138/Supplement%201/4415/482221/Liposome-Encapsulated-Cytarabine-and-Daunorubicin

Liposome-Encapsulated Cytarabine and Daunorubicin (CPX ... Liposome-Encapsulated Cytarabine and Daunorubicin (CPX-351) Induces Remission in Newly Diagnosed Pediatric Secondary Myeloid Malignancies ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7485353/

EMA Review of Daunorubicin and Cytarabine ... Secondary endpoints support the primary outcome, in particular an increased rate of hematopoietic stem cell transplantation, which is potentially the only ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2152265023002124

Real-World Experience With CPX-351 Treatment for Acute ... This study provides real-world survival outcomes data suggesting that CPX-351 is an effective treatment for both younger (<60 years) and older (≥60 years) ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30024784/

CPX-351 (cytarabine and daunorubicin) Liposome for ... Prior clinical studies demonstrated a sustained drug ratio and exposure in vivo and prolonged survival versus standard-of-care cytarabine plus ...

7. asco.org asco.org/abstracts-presentations/ABSTRACT313427

Five-year final results of a phase III study of CPX-351 ... After 5 y of follow-up, improved OS was maintained in this phase 3 study, supporting that CPX-351 has the ability to produce or contribute to long-term ...