What side effects are associated with this type of intervention?

The most common treatments for Polycythemia Vera, such as Ruxolitinib and Azacytidine, have notable side effects. Ruxolitinib, a JAK2 inhibitor, can cause cytopenias (anemia, thrombocytopenia), increased infection risk, and withdrawal syndrome with symptoms like fever and hypotension. Azacytidine, a chemotherapeutic agent, often leads to myelosuppression (neutropenia, anemia, thrombocytopenia), gastrointestinal issues (nausea, vomiting, diarrhea), and injection site reactions. Both treatments necessitate careful monitoring and dose adjustments.

What prior FDA approvals exist?

Ruxolitinib (Jakafi) is an FDA-approved JAK1/JAK2 inhibitor for the treatment of Polycythemia Vera in patients who have had an inadequate response to or are intolerant of hydroxyurea. This approval is based on its ability to reduce hematocrit levels and spleen size, and to improve symptoms. While Azacytidine is not specifically approved for PV, it is used in related myeloid malignancies, highlighting the role of chemotherapeutic agents in managing these conditions. Other FDA-approved treatments for PV include hydroxyurea and interferon-alpha.

What other types of research exist?

Promising novel alternatives for Polycythemia Vera patients include Pelabresib (CPI-0610), which has shown encouraging spleen and symptom responses in combination with Ruxolitinib in myelofibrosis patients. Additionally, imetelstat, an investigational antisense oligonucleotide directed against telomerase, has demonstrated partial and complete responses in advanced myelofibrosis, which may be relevant for PV treatment. These alternatives offer different mechanisms of action and potential benefits over traditional enzyme inhibition and chemotherapy.

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Anti-metabolite

Ruxolitinib + Azacytidine for Myelofibrosis and Myelodysplastic Syndrome/Myeloproliferative Neoplasm

Phase 2

Recruiting

Led By Naval Daver

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

Patients with a diagnosis of myelodysplastic syndrome/myeloproliferative neoplasm, unclassifiable (MDS/MPN-U) that require therapy

Must not have

Known positive for human immunodeficiency virus (HIV) or with known active infectious hepatitis, type A, B or C

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 30 days after completion of study treatment

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing two drugs, ruxolitinib phosphate and azacytidine, in patients with specific types of blood cancers that are hard to treat. Ruxolitinib blocks enzymes needed for cancer cell growth, while azacytidine kills cancer cells or stops them from dividing. Azacytidine is a well-known anticancer drug used in the treatment of various cancers, including breast cancer, melanoma, and colon cancer. The goal is to find a more effective treatment for these patients.

Who is the study for?

This trial is for patients with myelofibrosis or myelodysplastic/myeloproliferative neoplasm who need treatment. Eligible participants include those previously treated and relapsed, or newly diagnosed with intermediate/high risk. They must have an ECOG performance status of 0-2, acceptable organ function tests, and not be pregnant or at risk of pregnancy without taking precautions.

What is being tested?

The study is testing the combination of ruxolitinib phosphate (which blocks enzymes needed for cancer cell growth) and azacytidine (a chemotherapy drug that kills or stops cancer cells from growing). The goal is to see how well these drugs work together in treating specific blood disorders.

What are the potential side effects?

Potential side effects may include reactions related to immune system suppression such as infection risks, liver issues indicated by changes in bilirubin levels, kidney problems reflected by creatinine levels, and blood-related side effects like low platelet counts or neutrophil levels.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I can take care of myself and am up and about more than half of my waking hours.

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I have been diagnosed with MDS/MPN-U and need treatment.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have HIV or active hepatitis A, B, or C.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 30 days after completion of study treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 30 days after completion of study treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 30 days after completion of study treatment for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Myeloproliferative disease

Objective response rate (complete remission, partial remission, clinical improvement) in patients with myelofibrosis

Secondary study objectives

Incidence of adverse events defined as grade 3-4 clinically relevant non-hematologic toxicity or a serious adverse event that is felt to be drug related as assessed by the Common Terminology Criteria for Adverse Events version 4.0

Side effects data

From 2021 Phase 2 trial • 71 Patients • NCT01431209

23%

anemia

13%

Fever

11%

platelet count decreased

neutrophil count decreased

sepsis

lymphocyte count decreased

dyspnea

thromboembolic event

fever

hypoxia

hypercalcemia

hypophosphatemia

Acute kidney injury

sinus tachycardia

respiratory failure

fatigue

lung infection

ileus

hypotension

anorexia

cognitive disturbance

Investigations

pneumonitis

hypertension

Hepatobiliary - Other

nausea

dizziness

abdominal pain

diarrhea

pain in extremity

confusion

creatinine increased

delirium

pleural effusion

upper respiratory infection

vomiting

wound infection

Fall

cardiac disorder, Other

seizure

skin infection

syncope

tumor lysis syndome

Infections and infestiations - Other

Anemia

Musculoskeletal, Other

fracture

gait disturbance

gastric hemorrhage

sore throat

leukemia secondary to oncology chemotherapy

lymphedema

100%

80%

60%

40%

20%

Study treatment Arm

Diffuse Large B-cell Lymphoma (DLBCL)

Peripheral T-cell Non-Hodgkin Lymphoma (PTCL)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Arm II (MDS/MPN patients)Experimental Treatment3 Interventions

Patients with MDS/MPN receive ruxolitinib phosphate and azacytidine as in Arm I.

Group II: Arm I (MF patients)Experimental Treatment3 Interventions

Patients with MF receive ruxolitinib phosphate PO BID on days 1-28. Beginning course 4, patients also receive azacytidine SC or IV for 5 days. Treatment repeats every 28 days for 15 courses in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ruxolitinib Phosphate

2011

Completed Phase 2

~390

Azacitidine

2012

Completed Phase 3

~1440

0 / 3Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Ruxolitinib Phosphate, a JAK1/2 inhibitor, blocks the overactive Janus kinase pathway in Polycythemia Vera (PV), reducing abnormal blood cell proliferation. Azacytidine, a hypomethylating agent, incorporates into DNA and RNA to inhibit DNA methyltransferase, restoring normal gene function that controls cell growth and death. These treatments are vital for PV patients as they address the disease's root cause, helping to manage blood cell production and lower the risk of complications like thrombosis and disease progression.