Combination Drug Therapy for Aplastic Anemia and Myelodysplastic Syndrome

Overseen By Tapan Kadia, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Pregnancy, HIV, Uncontrolled illness, 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

Duration: 6 months

140 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a combination of drugs to treat aplastic anemia and myelodysplastic syndrome, conditions where the body doesn't produce enough blood cells. The study tests medicines such as methylprednisolone and horse anti-thymocyte globulin (a type of immunotherapy), which target certain immune cells and may help improve blood counts. It also uses drugs like filgrastim, which may boost white blood cell production to fight infections. This trial may suit adults with aplastic anemia or myelodysplastic syndrome who need frequent blood transfusions or experience severe fatigue. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications?

You must stop taking cytotoxic, immunosuppressive (except steroids), or targeted therapy at least 2 weeks before joining the study.

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

Research has shown that this combination therapy, which includes drugs like methylprednisolone, horse anti-thymocyte globulin, cyclosporine, filgrastim, and pegfilgrastim, treats blood disorders such as aplastic anemia and myelodysplastic syndrome. These treatments reduce immune cell activity and promote white blood cell growth, improving blood counts and aiding in infection defense.

Regarding safety, previous studies indicate that these drugs are generally well-tolerated. Methylprednisolone and cyclosporine are widely used, with usually manageable side effects. Horse anti-thymocyte globulin has been used for similar conditions, though it can sometimes cause allergic reactions due to its origin from horse blood. Filgrastim and pegfilgrastim often boost white blood cell counts and support the immune system, with bone pain as the most common side effect.

As this is a Phase 2 trial, earlier studies have already tested the combination's safety. Researchers now focus on its effectiveness for these specific conditions. This phase provides a clearer understanding of its effectiveness and safety for larger patient groups. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this combination drug therapy for aplastic anemia and myelodysplastic syndrome because it brings together multiple treatments in a novel way. Unlike the standard care, which typically involves standalone use of immunosuppressive agents or growth factors, this regimen combines anti-thymocyte globulin, cyclosporine, and growth factors like filgrastim and pegfilgrastim to potentially enhance the immune response and stimulate blood cell production more effectively. The incorporation of pegfilgrastim is particularly noteworthy, as it provides a long-acting boost to white blood cell counts, possibly leading to quicker recovery of the immune system. By targeting multiple pathways simultaneously, this approach may offer improved outcomes and a broader treatment response for patients with these challenging conditions.

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

Research has shown that a combination of specific medications can improve low blood counts in people with aplastic anemia and myelodysplastic syndrome. In this trial, participants will receive a combination therapy that includes methylprednisolone, cyclosporine, anti-thymocyte globulin, and either filgrastim or pegfilgrastim. Methylprednisolone and cyclosporine reduce the activity of certain immune cells that can harm blood cells. Filgrastim and pegfilgrastim boost the production of white blood cells, helping to prevent infections. Previous patients experienced better blood counts and fewer infections with this treatment. This combination therapy shows promise for managing these conditions. ^{1 2 3 6 7}

Who Is on the Research Team?

Tapan Kadia, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with aplastic anemia or low/intermediate-risk myelodysplastic syndrome. Eligible participants include those not currently fit for a stem cell transplant, off recent cytotoxic therapy, and with specific levels of bilirubin, AST, creatinine within set limits. They must have an ECOG status of ≤2, agree to contraception if applicable, and show a need for treatment due to symptoms like fatigue or infections.

Inclusion Criteria

I understand the study's requirements and have signed the consent form.

I stopped my cancer treatment 2 weeks ago and have recovered from major side effects.

I need treatment for my condition because it causes symptoms like severe tiredness, bleeding, or frequent infections.

Exclusion Criteria

I am HIV positive.

I do not have any serious illnesses or social situations that would stop me from following the study's requirements.

You have a known allergy to any of the medications being used in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive methylprednisolone, horse anti-thymocyte globulin, cyclosporine, and G-CSF for up to 6 months

6 months

Multiple visits for IV administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 6-12 months

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Anti-Thymocyte Globulin
• Cyclosporine
• Filgrastim
• Methylprednisolone
• Pegfilgrastim

Trial Overview

The study tests the combination of methylprednisolone (a steroid), horse anti-thymocyte globulin (an immune system suppressor), cyclosporine (another immunosuppressant), filgrastim and pegfilgrastim (both promote white blood cell growth) in treating aplastic anemia or myelodysplastic syndrome. The goal is to see if this regimen can improve blood counts and treat the disease effectively.

How Is the Trial Designed?

Group I: Treatment (methylprednisolone, hATG, cyclosporine, G-CSF) Experimental Treatment 5 Interventions

Patients receive methylprednisolone IV over 10 minutes on days 1-4 and IV or PO with taper over days 5-30. Patients also receive horse anti-thymocyte globulin IV over 8 hours daily on days 1-4, cyclosporine PO BID on days 1-180, and pegfilgrastim or pegfilgrastim biosimilar SC on day 5 and/or filgrastim SC beginning on day 5 and continuing until absolute neutrophil count recovers. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.

Anti-Thymocyte Globulin is already approved in European Union, United States for the following indications:

Approved in European Union as Thymoglobulin for:

• Prevention and treatment of acute rejection following organ transplantation
• Severe aplastic anemia

Approved in United States as Thymoglobulin for:

• Prevention and treatment of acute rejection following kidney transplantation
• Severe aplastic anemia

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 23 multiple myeloma patients, the combination of DCEP chemotherapy followed by a single dose of 6 mg PEGylated filgrastim (PEG-f) effectively mobilized peripheral blood stem cells, with 87% of patients collecting more than 2 x 10^6 CD34+ cells per kg body weight.

The treatment was well-tolerated, with only mild to moderate side effects reported, and no serious complications such as hospitalization or infections, indicating a favorable safety profile for this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DCEP chemotherapy followed by a single, fixed dose of pegylated filgrastim allows adequate stem cell mobilization in multiple myeloma patients. Zappasodi, P., Nosari, AM., Astori, C., et al.[2018]

In a phase III trial involving 111 patients with malignant lymphoma, pegfilgrastim was found to be non-inferior to filgrastim in reducing the duration of severe neutropenia after chemotherapy, with similar mean durations of 4.5 days for pegfilgrastim and 4.7 days for filgrastim.

The study demonstrated that a single subcutaneous dose of pegfilgrastim is as effective and safe as daily subcutaneous doses of filgrastim, making it a convenient alternative for managing neutropenia in lymphoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind trial of pegfilgrastim versus filgrastim for the management of neutropenia during CHASE(R) chemotherapy for malignant lymphoma. Kubo, K., Miyazaki, Y., Murayama, T., et al.[2022]

Filgrastim effectively reduces the duration of neutropenia in patients undergoing chemotherapy by inducing a dose-dependent increase in white blood cells, which helps prevent infections and mucositis.

The treatment is generally safe, with the most common side effect being mild to moderate bone pain, and it also has potential applications for other conditions like myelodysplastic syndrome and congenital neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topics in clinical pharmacology: filgrastim, a myeloid colony stimulating factor. Rogers, KM.[2019]

In a study involving 589 breast cancer patients, the proposed pegfilgrastim biosimilar showed comparable efficacy to both the US-licensed and EU-approved pegfilgrastim reference products, particularly in terms of the duration of severe neutropenia (DSN).

The safety profiles of the proposed biosimilar and the reference products were similar, with no unexpected adverse events reported, indicating that the biosimilar is a safe alternative for preventing chemotherapy-induced neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical confirmation to demonstrate similarity for a biosimilar pegfilgrastim: a 3-way randomized equivalence study for a proposed biosimilar pegfilgrastim versus US-licensed and EU-approved reference products in breast cancer patients receiving myelosuppressive chemotherapy. Desai, K., Misra, P., Kher, S., et al.[2022]

Tbo-filgrastim, a recombinant human G-CSF, has been shown to be as effective as Neupogen in reducing the duration of severe neutropenia in patients undergoing myelosuppressive chemotherapy, based on data from three phase III studies involving 677 patients.

The safety profile of tbo-filgrastim is comparable to Neupogen, with most adverse events related to chemotherapy rather than the drug itself, and only a small percentage of patients experiencing severe drug-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical safety of tbo-filgrastim, a short-acting human granulocyte colony-stimulating factor. Pettengell, R., Bias, P., Mueller, U., et al.[2018]

In a study of 645 cancer patients receiving chemotherapy, pegfilgrastim was administered more correctly as primary prophylaxis compared to filgrastim/lenograstim, with adherence rates of 66% versus 47%.

The study found that while pegfilgrastim was used correctly in timing 93.2% of the time, filgrastim/lenograstim was only used correctly 61.5% of the time, indicating a need for better education and predictive tools for identifying high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Granulocyte colony-stimulating factors used in clinical practice: PoloNord Registry-Based Cohort Italian Study. Fagnani, D., Isa, L., Verga, MF., et al.[2018]

Pegfilgrastim, a long-acting form of granulocyte colony-stimulating factor (G-CSF), allows for once-per-cycle dosing, making it more convenient than filgrastim, which requires daily injections.

Clinical trials have shown that pegfilgrastim is as safe and effective as filgrastim in reducing the duration of severe neutropenia in patients undergoing chemotherapy for various cancers, including breast cancer and lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegfilgrastim use during chemotherapy: current and future applications. Wolf, T., Densmore, JJ.[2018]

Balugrastim, a novel long-acting granulocyte colony-stimulating factor, has a half-life of approximately 19 days and was found to be noninferior to pegfilgrastim in reducing the duration of severe neutropenia in breast cancer patients undergoing chemotherapy.

In clinical trials, balugrastim demonstrated a comparable efficacy and safety profile to pegfilgrastim, with mild to moderate bone pain being the only related adverse event, indicating it is a well-tolerated option for managing chemotherapy-induced neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in the treatment of chemotherapy-induced neutropenia: focus on balugrastim. Ghidini, M., Hahne, JC., Trevisani, F., et al.[2020]

In a phase 3 trial involving 197 previously untreated patients with severe aplastic anemia, the addition of eltrombopag to standard immunosuppressive therapy significantly improved the complete response rate at 3 months from 10% to 22%.

Eltrombopag also accelerated the time to response, with patients receiving it showing a median time to first response of 3.0 months compared to 8.8 months for those not receiving it, all without increasing the incidence of severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eltrombopag Added to Immunosuppression in Severe Aplastic Anemia. Peffault de Latour, R., Kulasekararaj, A., Iacobelli, S., et al.[2023]

Peg-filgrastim (PEG-FIL) is effective in mobilizing hematopoietic progenitor cells (HPC) more quickly than traditional G-CSF, allowing for a single-dose administration that reduces the number of apheresis procedures needed after chemotherapy.

A single dose of 6 mg PEG-FIL is effective for HPC mobilization, but increasing the dose to 12 mg does not enhance this effect, and higher doses for steady-state mobilization are not cost-effective compared to G-CSF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-active granulocyte colony-stimulating factor for peripheral blood hematopoietic progenitor cell mobilization. Martino, M., Laszlo, D., Lanza, F.[2018]

Immunosuppressive therapy (IST) is crucial for treating aplastic anemia, and this review summarizes the pharmacological mechanisms and therapeutic effects of key drugs used in IST, including ATG/ALG and CsA.

The review aims to guide clinical therapy by discussing the application methods, reasonable dosages, and potential synergistic effects of these treatments, which are essential for optimizing patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunosuppressive therapy for aplastic anemia--review]. Xu, CY.[2016]

In a study of 89 aplastic anemia patients, the combination of cyclosporine (CSA) and eltrombopag (EPAG) showed similar overall response rates to the combination of CSA, EPAG, and antithymocyte globulin (ATG), indicating that CSA + EPAG may be an effective alternative treatment.

The CSA + EPAG combination resulted in fewer side effects compared to the standard treatment with ATG, with a mortality rate of 7.8% in the ATG group and no deaths in the CSA + EPAG group, suggesting a potentially safer option for newly diagnosed patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyclosporine plus eltrombopag in the treatment of aplastic anemia with or without antithymocyte immunoglobulin: A multicenter real-world retrospective study. Chen, M., Liu, Q., Gao, Y., et al.[2023]

The standard treatment for severe aplastic anemia, horse anti-thymocyte globulin plus cyclosporine, achieves a hematologic response in 60 to 70% of patients, but there is a significant risk of relapse (30 to 40%) and clonal evolution (10 to 15%).

Despite advances in treatment options, no new regimens have significantly improved hematologic response rates or reduced relapse and clonal evolution, making the current standard therapy still the most effective initial approach for managing severe aplastic anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current management of severe acquired aplastic anemia. Scheinberg, P.[2016]

In a trial involving 88 patients with myelodysplastic syndrome (MDS), those treated with combined antithymocyte globulin (ATG) and cyclosporine (CSA) showed a significant hematologic response at 6 months, with 13 out of 45 patients responding compared to only 4 out of 43 in the best supportive care group.

Despite the positive hematologic response, the study found no significant difference in two-year transformation-free survival (TFS) or overall survival (OS) between the ATG+CSA group and the best supportive care group, indicating that while ATG+CSA can improve blood counts, it may not extend survival or prevent disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunosuppressive therapy for patients with myelodysplastic syndrome: a prospective randomized multicenter phase III trial comparing antithymocyte globulin plus cyclosporine with best supportive care--SAKK 33/99. Passweg, JR., Giagounidis, AA., Simcock, M., et al.[2018]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01624805?term=AREA%5BConditionSearch%5D(Equine)%20AND%20AREA%5BOverallStatus%5D(NOT_YET_RECRUITING%20OR%20RECRUITING%20OR%20AVAILABLE)&rank=10

Study Details | Methylprednisolone, Horse Anti-Thymocyte ...

This may help to fight infections and help improve the white blood cell count. Giving methylprednisolone and horse anti-thymocyte globulin together with ...

2.

trialx.com

trialx.com/clinical-trials/listings/268982/methylprednisolone-horse-anti-thymocyte-globulin-cyclosporine-filgrastim-andor-pegfilgrastim-or-pegfilgrastim-biosimilar-in-treating-patients-with-aplastic-anemia-or-low-or-intermediate-risk-myelodysplastic-syndrome/

Methylprednisolone, Horse Anti-Thymocyte Globulin ...

Methylprednisolone and cyclosporine work to suppress immune cells called lymphocytes. This may help to improve low blood counts in aplastic ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01624805

Methylprednisolone, Horse Anti-Thymocyte Globulin, ...

Methylprednisolone and cyclosporine work to suppress immune cells called lymphocytes. This may help to improve low blood counts in aplastic anemia and ...

4.

drugpatentwatch.com

drugpatentwatch.com/p/biologics/clinical-trials/profile/drugname/tbo-filgrastim?srsltid=AfmBOoqN3ym9NplDX69lbnPay2arIQ71fKQ2Fz4r04yf2A_I4mNYtQv4

Biosimilar Clinical Trials for tbo-filgrastim

Biosimilar Clinical Trials for tbo-filgrastim ; NCT01624805 ↗, Methylprednisolone, Horse Anti-Thymocyte Globulin, Cyclosporine, Filgrastim, and/ ...

5.

mdanderson.org

mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2012-0334.html

Phase II Study of Horse Anti-Thymocyte Globulin (hATG) ...

Methylprednisolone and cyclosporine work to suppress immune cells called lymphocytes. This may help to improve low blood counts in aplastic anemia and ...

6.

withpower.com

withpower.com/trial/phase-3-anemia-aplastic-5-2012-57b67

Combination Drug Therapy for Aplastic Anemia and ...

Methylprednisolone and cyclosporine work to suppress immune cells called lymphocytes. This may help to improve low blood counts in aplastic anemia and ...

7.

go.drugbank.com

go.drugbank.com/conditions/DBCOND0028035

Aplastic Anemia (DBCOND0028035)

Methylprednisolone, Horse Anti-Thymocyte Globulin, Cyclosporine, Filgrastim, and/or Pegfilgrastim or Pegfilgrastim Biosimilar in Treating Patients With ...