CLINICAL TRIAL

Venetoclax for Myelodysplastic Syndromes

Recruiting · 18+ · All Sexes · Kansas City, MO

This study is evaluating whether a combination of chemotherapy and immunotherapy may help treat acute myeloid leukemia.

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About the trial for Myelodysplastic Syndromes

Eligible Conditions
Acute Myeloid Leukemia (AML) · Leukemia · Myelodysplastic Syndromes · Leukemia, Myeloid, Acute · Secondary Acute Myeloid Leukemia (Secondary AML, sAML) · Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome · Therapy-Related Acute Myeloid Leukemia · Leukemia, Myeloid

Treatment Groups

This trial involves 2 different treatments. Venetoclax is the primary treatment being studied. Participants will all receive the same treatment. There is no placebo group. The treatments being tested are in Phase 2 and have already been tested with other people.

Main TreatmentA portion of participants receive this new treatment to see if it outperforms the control.
Venetoclax
DRUG
Biopsy
PROCEDURE
Azacitidine
DRUG
Pembrolizumab
BIOLOGICAL
Control TreatmentAnother portion of participants receive the standard treatment to act as a baseline.
Venetoclax
DRUG
Biopsy
PROCEDURE
Azacitidine
DRUG

About The Treatment

Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Venetoclax
FDA approved
Biopsy
2014
Completed Phase 2
~1570
Azacitidine
FDA approved
Pembrolizumab
FDA approved

Eligibility

This trial is for patients born any sex aged 18 and older. You must have received newly diagnosed for Myelodysplastic Syndromes or one of the other 7 conditions listed above. There are 10 eligibility criteria to participate in this trial as listed below.

Inclusion & Exclusion Checklist
Mark “yes” if the following statements are true for you:
Creatinine clearance (CrCl) should be calculated per institutional standard. show original
Newly diagnosed and pathologically-confirmed, previously untreated AML as defined by World Health Organization (WHO) criteria. Bone marrow biopsy, or aspirate or peripheral blood that were obtained up to 3 weeks before signing consent are allowed for purposes of confirming AML diagnosis for eligibility purposes. Secondary AML arising from prior myelodysplastic syndrome (MDS), as long as they have not received more than full cycle of hypomethylating agent therapy for MDS, and therapy related (t)-AML are also allowed. AML arising from prior antecedent hematologic disorders defined as MDS, mycoplasma pneumoniae (MPN), or aplastic anemia are allowed. Note 1: Patients must have evidence of bone marrow involvement on aspirate or biopsy. Patients with only extramedullary disease and no bone marrow involvement will be excluded. Note 2: Every effort should be made to get an aspirate for central flow assessment at screening and all subsequent required time points, but in cases where an aspirate cannot be collected-including dry taps-the patient will not be excluded and assessments will be performed on peripheral blood (PB) which should be collected at every time that bone marrow (BM) is collected. Note 3: Some patients with AML require initiation of therapy quickly after diagnosis, and full metaphase karyotype results in some centers can take 2-3 weeks to result. To avoid this issue being an impediment to accrual to study or to cause delays in initiation of therapy in patients who need fast initiation of therapy, we allow use of karyotype and/or fluorescence in situ hybridization (FISH) results on samples from blood or marrow that were obtained up to 3 weeks before signing consent for purposes of eligibility and stratification. In any case, results from FISH or karyotype should exclude presence of core-binding factor (CBF) abnormalities by time of randomization
Age >= 60 years
Patients who are ineligible for intensive chemotherapy according to treating physician's assessment or who refuse intensive chemotherapy
You have a performance status of 0-3. show original
Prior use of lenalidomide, erythropoiesis-stimulating agents (ESAs), and growth factors is allowed if used to treat prior MDS. AML must be previously untreated except for hydroxyurea, or all-trans retinoic acid (ATRA) for suspicion of APL but both should be discontinued prior to initiation of study therapy. Hypomethylating agents are not allowed to have been used for AML therapy. If hypomethylating agent therapy was used for prior MDS or MPN therapy then it should not have exceeded one full cycle. Note: One dose of prophylactic intrathecal therapy is allowed during or before screening if a lumbar puncture is performed to rule out central nervous system (CNS) involvement
Hydroxyurea or leukopheresis are allowed for management of hyperleukocytosis, as well as ATRA, before initiation of study therapy. White blood cell (WBC) count must be < 25 x 10^9/L to start on study therapy per venetoclax label. Hydroxyurea and ATRA may be administered up to one day prior to start of study treatment
Intermediate-risk or poor risk AML as well as favorable risk by National Comprehensive Cancer Network (NCCN)/European LeukemiaNet (ELN) with the exception of "good-risk" cytogenic profile (i.e., for eligibility patient should lack the presence of t(8;21), (inv[16] or t[16;16]), or t(15;17) by full cytogenetics or FISH). Clarification: We allow use of karyotype and/or FISH results (as well as FLT3 results) on samples from blood or marrow that were obtained up to 3 weeks before signing consent for purposes of eligibility and stratification. Adverse karyotype can be determined based on FISH results (e.g., loss of chromosome 7 or 5 or 3 or more abnormalities) based on the specific probes used in the FISH. If results of full metaphase karyotype are not available and the available FISH results do not suggest an adverse karyotype, and there is a need to initiate therapy before those full results are available, then the patient can be stratified into the unknown/intermediate NCCN cytogenetic group for randomization purposes. In any case, results from FISH or karyotype should show that CBF abnormalities are NOT present by at time of randomization as the presence of CBF abnormalities is an exclusion factor Creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (CrCl) >= 60 mL/min for patient with creatinine levels > 1.5 x institutional ULN
Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for patients with total bilirubin levels > 1.5 x ULN
GFR can be used in place of CrCl or Cr show original
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Odds of Eligibility
Unknown<50%
Be sure to apply to 2-3 other trials, as you have a low likelihood of qualifying for this one.Apply To This Trial
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Approximate Timelines

Please note that timelines for treatment and screening will vary by patient
Screening: ~3 weeks
Treatment: varies
Reporting: Up to 3 years
This trial has approximate timelines as follows: 3 weeks for initial screening, variable treatment timelines, and reporting: Up to 3 years.
View detailed reporting requirements
Trial Expert
Connect with the researchersHop on a 15 minute call & ask questions about:
- What options you have available- The pros & cons of this trial
- Whether you're likely to qualify- What the enrollment process looks like

Measurement Requirements

This trial is evaluating whether Venetoclax will improve 2 primary outcomes, 1 secondary outcome, and 8 other outcomes in patients with Myelodysplastic Syndromes. Measurement will happen over the course of At day 14 and at time of count recovery.

Expression of PD-1, PD-L1 in acute myeloid leukemia (AML) bone marrow (BM)
AT DAY 14 AND AT TIME OF COUNT RECOVERY
An association of clinical response with the expression of PD-L1 AML BM cells will be assessed by a Pearson chi-square test on a 2x2 table of frequencies.
Proportion of patients who develop severe toxicity
UP TO CYCLE 2 (EACH CYCLE IS 28 DAYS)
Dynamic change of immune subsets
BASELINE UP TO CYCLE 6 (EACH CYCLE IS 28 DAYS)
Statistical analyses of the frequency of CD8+, CD4+, Foxp3 regulatory T cells (Tregs), CD8+/Foxp3+ Tregs, central memory T cell (TCM)/effector memory T cell re-expressed CD45RA (TEMRA), effector memory T cell (TEM)/TEMRA, the percentage of Ki67 and GzmB in PD-1+, Eomes+ CD8 T cells to compare changes over time from baseline to several time-points will be performed by using mixed effects modeling with a Benjamini-Hochberg correction to control for false discovery rates.
Percentage of patients with minimal residual disease negative complete remission (MRD-CR) or MRD-complete remission with incomplete count recovery (Cri) with azacitadine (AZA) + venetoclax (VEN) with MK-3475 (pembrolizumab)
UP TO 6 CYCLES (EACH CYCLE IS 28 DAYS)
Percentage of patients with minimal residual disease negative complete remission (MRD-CR) or MRD-complete remission with incomplete count recovery (Cri) with azacitidine (AZA) + venetoclax (VEN) with MK-3475 (pembrolizumab)
UP TO 6 CYCLES (EACH CYCLE IS 28 DAYS)
Cytokine panel analysis
AT DAY 30 (AFTER ADMINISTRATION OF PEMBROLIZUMAB AND COUNT RECOVERY) AND AFTER CYCLES 2, 4, AND 6 (EACH CYCLE IS 28 DAYS)
IFN-gamma+/CD3+/ CD4+ or IFN-gamma+/CD3+/CD8+ events will be gated and percentages of the total CD4+ and CD8+ T cells will be determined. Will compare levels of leukemia specific T-cell.
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Patient Q & A Section

Please Note: These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

What is myelodysplastic syndromes?

MDS comprises a diverse group of clinically and histologically similar disorders, which can be distinguished chiefly on clinical, cytogenetic, and biochemical features. The clinical definition, which includes a peripheral blood monocytosis of less than 1200/microl, remains useful in some respects but is likely to reflect an advanced disease (with high prevalence of SRS).

Anonymous Patient Answer

How many people get myelodysplastic syndromes a year in the United States?

Around 45,000 people will be diagnosed with MDS/PDS every year in the USA, making these the most common form of blood cancers, the second-most common type of blood cancer overall after non-Hodgkin's lymphoma, and the biggest cause of life-threatening leukemia in females. More than half of MDS/PDS cases occurring in the USA are related to MCP1 fusion gene, FLT3, or mutations of FLT3. Around 30% of MDS and MDS-DS are linked to JAK2, KIT, or TP53 mutations. Around 60% of MDS/MDS-PDS are the result of JAK2 V617F translocations.

Anonymous Patient Answer

What causes myelodysplastic syndromes?

As MDS continues to be recognized as a serious disease, a better understanding of its origin and biological mechanisms of action is necessary in order to provide innovative treatments to this patient population.

Anonymous Patient Answer

What are the signs of myelodysplastic syndromes?

This guideline has been developed to guide the use of MDS diagnostic criteria for the appropriate diagnosis. The recommendation about the use of the WHO criteria is not applicable in all types of MDS. A diagnosis should only apply to patients who have the requisite clinical/laboratory criteria, as is confirmed by at least two of the following four sets of criteria: WHO or EU/EEU/CFDG criteria for MDS, CMLD criteria or WHO criteria for acute leukemia, and a peripheral blast count greater than 20% of nuclei with a clone. The authors conclude by advising to follow the International Working Group criteria (2016).

Anonymous Patient Answer

Can myelodysplastic syndromes be cured?

Treatment with a bone marrow-stimulating agent such as thalidomide, lenalidomide or bortezomib, can prolong survival and improve quality of life in patients with relapsed/refractory myelodysplastic syndromes.

Anonymous Patient Answer

What are common treatments for myelodysplastic syndromes?

In MDS, the majority of treatment regimes use anthracyclines and lenalidomide. For elderly patients, consolidation (proton-beam radiation and azacitidine) may be necessary. For younger patients, the decision to use consolidation depends on the number of chromosomal abnormalities, patient age, and response after one course of therapy.

Anonymous Patient Answer

What are the common side effects of venetoclax?

In a recent study, findings indicate that venetoclax is well tolerated in most patients with MDS, particularly as given as monotherapy. Because it represents an exciting new treatment option in older patients with MDS, further studies are warranted.

Anonymous Patient Answer

What are the chances of developing myelodysplastic syndromes?

It was concluded that the risks of developing MS depended on how long the disease was in progress and if any previous procedures were performed. It was also noted that those with high counts of white blood cell blasts have a higher risk of developing MS.

Anonymous Patient Answer

What is the latest research for myelodysplastic syndromes?

Current research seems to identify the pathophysiology of these disorders but still has significant gaps in its understanding. The disease may not be a consequence of bone marrow dysfunction. Current research supports the use of erythropoietin in patients with myelodysplastic syndromes as well as the use of cladribine as a treatment. Current research also supports the identification of the mutations that cause these diseases.

Anonymous Patient Answer

What is the average age someone gets myelodysplastic syndromes?

Age of onset is very variable among different types. The average age at diagnosis when in myelodysplastic syndromes is 64 years old, with an estimated 1-2 years average interval between onset and diagnosis. Therefore, age is an important aspect to look at when considering the diagnosis.

Anonymous Patient Answer

Is venetoclax safe for people?

Venetoclax, given as maintenance or in a phase 3 trial, appears to be well tolerated in people with myelodysplastic syndrome and refractory AML. Future studies will need to confirm whether these data extend to people with MDS and chronic myelomonocytic leukemia as a full-blown phase 3 trial in this indication may be warranted. Additional larger dose phase 3 studies with long-term follow-up are still needed to confirm safety.

Anonymous Patient Answer

Does venetoclax improve quality of life for those with myelodysplastic syndromes?

These data suggest overall improvement in HRQOL through venetoclax across different domains of HRQOL in participants with MDS. More specifically, venetoclax led to improvement in physical functioning, including a decrease in fatigue and improvement in energy, fatigue, and general HRQOL.

Anonymous Patient Answer
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