Lenalidomide +/− Epoetin Alfa for Myelodysplastic Syndrome

Not currently recruiting at 589 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must be taking: Lenalidomide

Must not be taking: Cytotoxic agents

Disqualifiers: Pregnancy, Uncontrolled hypertension, HIV, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether lenalidomide (Revlimid) alone or combined with epoetin alfa (Eprex, Epogen, or Procrit) is more effective for treating myelodysplastic syndrome (MDS) and anemia. Lenalidomide may block blood flow to MDS cells, while epoetin alfa could boost immune cells in the blood. The trial seeks participants diagnosed with MDS for at least three months who have significant anemia affecting their daily life. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that participants stop all non-transfusion therapy for myelodysplastic syndrome (MDS) for 28 days before starting the study treatment. This includes all types of growth factors.

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

Earlier studies have raised some safety concerns about lenalidomide. Specifically, 67.2% of patients experienced serious side effects, and 35.5% discontinued treatment due to these effects. While these adverse effects are common, not everyone will experience them.

When combined with epoetin alfa, lenalidomide appears generally safe. Research shows that most patients tolerate this treatment well. Although specific side effects were not listed, studies suggest that patients can manage this treatment without major issues.

Side effects can vary from person to person, but these studies provide a clearer idea of what to expect. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for myelodysplastic syndrome focus on managing symptoms and supporting blood cell production. However, lenalidomide stands out because it not only boosts red blood cell production but also modulates the immune system and inhibits cancer cell growth. Researchers are excited about combining lenalidomide with epoetin alfa, which further stimulates red blood cell production, potentially leading to more effective management of anemia associated with the condition. Together, these treatments could offer a more comprehensive approach by addressing both the root causes and symptoms of myelodysplastic syndrome.

What evidence suggests that this trial's treatments could be effective for myelodysplastic syndrome and anemia?

Research has shown that lenalidomide, which participants in this trial may receive, effectively treats myelodysplastic syndrome (MDS), particularly in patients with a specific genetic feature called del(5q). In these patients, lenalidomide can significantly reduce the risk of disease progression and improve anemia. For patients without the del(5q) feature, about 27% respond to lenalidomide, and evidence suggests it may still help them live longer.

In this trial, some participants will receive lenalidomide combined with epoetin alfa. This combination treatment appears promising for those with MDS and anemia. Studies have found that this combination improves red blood cell counts more effectively than lenalidomide alone. Specifically, nearly 39% of patients on the combination showed significant improvement, compared to about 16% with just lenalidomide. ^{1 4 6 7 8}

Who Is on the Research Team?

Amit K Verma

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

Adults diagnosed with low- or intermediate-1-risk myelodysplastic syndrome (MDS) and anemia, who have not responded to erythropoietin treatment or are unlikely to respond. Participants must have adequate organ function, no severe allergies to thalidomide, no recent malignancies other than MDS, and not be pregnant. They should also not have had any MDS treatments in the last 28 days.

Inclusion Criteria

I haven't received any non-transfusion treatments for MDS in the last 28 days.

I have been diagnosed with MDS or CMML for at least 3 months.

I have been diagnosed with MDS or CMML with low white blood cell count for 3 months or more.

Exclusion Criteria

Women pregnant or breastfeeding

Serious medical condition, unstable medical co-morbidity, or psychiatric illness preventing informed consent or placing subject at unacceptable risk

I have been treated with lenalidomide before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive lenalidomide with or without epoetin alfa for 4 cycles of 28 days each

16 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

2 visits (in-person)

Extension

Participants who achieve a major erythroid response may continue treatment beyond 4 cycles

Variable

What Are the Treatments Tested in This Trial?

Interventions

• Epoetin Alfa
• Lenalidomide

Trial Overview The trial is testing whether lenalidomide works better alone or combined with epoetin alfa for treating anemia in patients with MDS. Lenalidomide may inhibit tumor growth by cutting off blood supply to cancer cells while epoetin alfa could boost immune cell numbers.

How Is the Trial Designed?

Group I: Arm B (lenalidomide, epoetin alfa) Experimental Treatment 4 Interventions

Patients receive lenalidomide PO QD on days 1-21 and epoetin alfa SC once weekly. Patients undergo bone marrow biopsy at screening and during follow-up. Patients undergo blood specimen collection on study.

Group II: Arm A (lenalidomide) Active Control 3 Interventions

Patients receive lenalidomide PO QD on days 1-21. Patients undergo bone marrow biopsy at screening and during follow-up. Patients undergo blood specimen collection on study.

Lenalidomide is already approved in European Union, United States for the following indications:

Approved in European Union as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Approved in United States as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

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

Lenalidomide (REVLIMID®) is an effective treatment for multiple myeloma and transfusion-dependent anemia in myelodysplastic syndromes, showing better activity and less neurotoxicity compared to its predecessor, thalidomide.

This drug has multiple beneficial properties, including anti-inflammatory and antiangiogenic effects, and may play a significant role in treating various cancers beyond its current approved uses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential of immunomodulatory drugs in the treatment of solid tumors. Dalgleish, A., Galustian, C.[2018]

Lenalidomide is an effective treatment for transfusion-dependent anemia in lower-risk myelodysplastic syndromes (MDS), particularly in patients with the deletion 5q chromosomal abnormality, but it also shows clinical activity in those without this specific abnormality.

The use of lenalidomide in MDS exemplifies reciprocal translational research, where laboratory findings informed clinical applications, enhancing our understanding of both the drug's mechanisms of action and the biology of MDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in myelodysplastic syndromes: an erythropoiesis-stimulating agent or more? Komrokji, RS., Lancet, JE., List, AF.[2021]

In a phase III trial with 195 patients suffering from lower-risk, non-del(5q) myelodysplastic syndromes (MDS), the combination of lenalidomide (LEN) and epoetin (EPO) alfa resulted in a significantly higher major erythroid response (28.3%) compared to LEN alone (11.5%).

The combination treatment not only increased the response rate but also provided a longer duration of response, with a median major erythroid response duration of 23.8 months for the LEN-EPO group compared to 13 months for LEN alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide-Epoetin Alfa Versus Lenalidomide Monotherapy in Myelodysplastic Syndromes Refractory to Recombinant Erythropoietin. List, AF., Sun, Z., Verma, A., et al.[2022]

Lenalidomide has become a crucial treatment option for multiple myeloma and del-5q myelodysplastic syndromes, and it has been tested for various other cancers, showcasing its broad therapeutic potential.

The drug received FDA approval for use in combination with dexamethasone for previously treated multiple myeloma, highlighting its efficacy and safety in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: a novel anticancer drug with multiple modalities. Galustian, C., Dalgleish, A.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12071050/

Lenalidomide Efficacy in Patients with MDS and Del-5q Conclusions: Lenalidomide was highly effective in patients with the del(5)q syndrome and also in those with isolated del(5)q, other than del(5)q ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2152265022001525#!

Impact of Lenalidomide Treatment on Overall Survival in ... In the MDS-005 trial, only 27% of patients with non-del(5q) MDS responded to lenalidomide and a trend toward improved OS was only observed for patients with ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa041668

Efficacy of Lenalidomide in Myelodysplastic Syndromes These findings suggest that lenalidomide restores red-cell production in part by eliminating ineffective myelodysplastic clones but does not ...

4. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.30585

Lenalidomide use in myelodysplastic syndromes: Insights into ... 58 In this study, patients who achieved an erythroid response had an 86% reduction in risk of disease progression and an 80% reduction in ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3573434/

Efficacy and safety of lenalidomide in patients with ... A multicenter phase II trial evaluated the safety and efficacy of lenalidomide in 47 higher-risk MDS patients with 5q deletion, reporting a 27% response rate, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT00065156

Study Details | NCT00065156 | Lenalidomide Safety/ ... This study is a multicenter, single-arm, open-label study of oral lenalidomide monotherapy administered to red blood cell (RBC) transfusion-dependent ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2152265024023656

Lenalidomide in Transfusion-Dependent IPSS Low- or ... Grade 3/4 treatment-emergent adverse events were experienced by 67.2% of the safety population, and these led to discontinuation in 35.5% of patients. There ...

8. targetedonc.com targetedonc.com/view/low-dose-lenalidomide-lowers-risk-of-transfusion-dependency-provides-other-benefits-in-myelodysplastic-syndrome

Low-Dose Lenalidomide Lowers Risk of Transfusion ... The SINTRA-REV trial showed lower risk of transfusion dependency in patients with MDS treated with lenalidomide.