Recruiting PHASE1 Myelodysplastic Syndromes, de Novo

New treatment option for Myelodysplastic Syndromes, de Novo

Official title Venetoclax Basket Trial for High Risk Hematologic Malignancies

ClinicalTrials.gov ID: NCT05292664

What this study is testing

What is Venetoclax?

Venetoclax is an investigational medicine, given as a pill taken by mouth, being studied as a potential treatment for myelodysplastic syndromes, de novo.

Also referred to as Venclexta.

Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.

What it's testing: This trial is evaluating the safety and tolerability of venetoclax with chemotherapy in pediatric and young adult patients with hematologic malignancies, including myelodysplastic syndrome (MDS), acute myeloid leukemia derived from myelodysplastic syndrome (MDS/AML), and acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL). The names of the study drugs involved in this study are below.

Phase 1: an early, usually small safety study

A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.

Who can take part

Ages 1 to 40

You may be able to join if

Cohort A
MDS, AML arising from MDS (MDS/AML), therapy related myeloid neoplasm (tMDS/AML) meeting at least one of the following criteria:
MDS with excess blasts (\>10%)
MDS with blasts \<10% with high-risk features
MDS refractory to initial treatment

You likely can't join if

Cohort A Exclusion Criteria
Use of strong or moderate CYP3A inhibitors/inducers within 3 days of study entry
Individuals who have had a stem cell transplant and are still receiving treatment for GVHD or GVHD prophylaxis, or who have evidence of acute GVHD
Individuals with known active hepatitis; baseline testing not required.
Patients with systemic infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate...
Patients known to have human immunodeficiency virus (HIV) infection; baseline testing for HIV is not required.

See the full eligibility criteria

Who can join

Cohort A
MDS, AML arising from MDS (MDS/AML), therapy related myeloid neoplasm (tMDS/AML) meeting at least one of the following criteria:
MDS with excess blasts (\>10%)
MDS with blasts \<10% with high-risk features
MDS refractory to initial treatment
Relapsed MDS
MDS/AML: May be newly diagnosed or relapsed/refractory disease.
Therapy related myeloid neoplasm (tMDS/AML): May be initial or relapsed/refractory disease.
Note: MDS or MDS/AML may be derived from a germline predisposition to myeloid malignancy as long as that condition does not confer increased toxicity to treatment.
Age ≤ 40 years of age, except the following people that must be \<18 years to enroll
people with MDS/AML that have not received prior therapy
people enrolled onto Dose level -2.
Lansky/Karnofsky performance status ≥ 50%
Participants must have fully recovered from the acute toxic effects of all and meet all of the following criteria:
Myelosuppressive chemotherapy: 14 days, or 5 half-lifes (whichever is shorter) must have elapsed since the completion of myelosuppressive therapy. Individuals may have received any of the following medications without a...
Standard maintenance therapy: dexamethasone/prednisone, vincristine, 6MP, low dose methotrexate)
Hydroxyurea
Intrathecal chemotherapy with methotrexate, hydrocortisone and/or cytarabine.
Radiation therapy (XRT):
Total Body Irradiation (TBI) or cranial radiation therapy: Must have been completed more than 90 days prior to study entry
XRT for chloroma does not require a washout period.
Palliative XRT does not require a washout
Small molecule inhibitors (BCR-ABL or FLT3 inhibitors, for example): 7 days, or 5 half-lifes, whichever is shorter) must have elapsed since the completion of therapy. For agents that have known adverse events occurring...
Immunotherapy: At least 30 days after the administration of any type of immunotherapy, including, but not limited to, tumor vaccines, chimeric antigen receptor (CAR) therapy, other immune effector cell therapy and...
Monoclonal antibodies: At least 3 half-lives of the antibody
Prior hematopoietic stem cell transplant (HSCT):
Allogeneic HSCT \> 90 days of study entry
No evidence of graft-versus-host-disease (GVHD)
Adequate organ function, as defined by
Serum alanine aminotransferase (ALT) ≤5X upper limit of normal (ULN)
Direct bilirubin ≤ 3X
Ejection fraction ≥ 50% or shortening fraction of ≥ 24% on screening echocardiogram.
Female participants of childbearing potential must have a negative urine or serum HCG prior to study entry and at the start of therapy. All females of childbearing potential must refrain from breastfeeding during study...
Dyskeratosis Congenita or associated telomeropathies
Fanconi Anemia
Nijmegen Breakage
Other related disorders with high risk of toxicity may be eligible for this cohort after discussion with the Sponsor-Investigator.
And meets at least one the following disease characteristics:
MDS with excess blasts (\>10%)
MDS with blasts \<10% with high-risk features
MDS refractory to initial treatment
Relapsed MDS
MDS/AML: May be newly diagnosed or relapsed/refractory disease.
Therapy related myeloid neoplasm (tMDS/AML): May be initial or relapsed/refractory disease.
Age ≤ 40 years of age
Lansky/Karnofsky performance status ≥ 50%
Participants must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study and meet all of the following criteria:
Myelosuppressive chemotherapy: 14 days, or 5 half-lifes (which ever is shorter) must have elapsed since the completion of myelosuppressive therapy. Individuals may have received any of the following medications without...
Standard maintenance therapy: dexamethasone/prednisone, vincristine, 6MP, low dose methotrexate
Hydroxyurea
Intrathecal chemotherapy with methotrexate, hydrocortisone and/or cytarabine.
Radiation therapy (XRT):
Total Body Irradiation (TBI) or cranial radiation therapy: Must have been completed more than 90 days prior to study entry
XRT for chloroma does not require a washout period.
Palliative XRT does not require a washout
Small molecule inhibitors (BCR-ABL or FLT3 inhibitors, for example): 7 days, or 5 half-lifes, whichever is shorter) must have elapsed since the completion of therapy. For agents that have known adverse events occurring...
Immunotherapy: At least 30 days after the administration of any type of immunotherapy, including, but not limited to, tumor vaccines, chimeric antigen receptor (CAR) therapy, other immune effector cell therapy and...
Monoclonal antibodies: At least 3 half-lives of the antibody
Prior hematopoietic stem cell transplant (HSCT): Must meet all of the following conditions:
Allogeneic HSCT \> 90 days of study entry
No evidence of graft-versus-host-disease (GVHD)
Adequate organ function, as defined by
Serum alanine aminotransferase (ALT) ≤5X upper limit of normal (ULN)
Direct bilirubin ≤ 3X upper limit of normal for age and institution.
Ejection fraction ≥ 50% or shortening fraction of ≥ 24% on screening echocardiogram.
Because of the teratogenic effects of venetoclax on developing fetuses, female participants of childbearing potential must have a negative urine or serum HCG prior to study entry and at the start of therapy. All females...
For ALL/MPAL: Bone marrow involvement ≥ 5% by aspirate morphology or ≥ 1% assessable by flow cytometry or validated molecular minimal residual disease (MRD) testing
For LBL: Radiographically detectable mass or lymph node involvement
Part II: Histologically confirmed diagnosis of one of the following:
T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LBL) in first or greater relapse or refractory to at least 1 prior remission induction attempt.
For T-ALL: Bone marrow involvement ≥ 5% by aspirate morphology or ≥ 1% assessable by morphology, flow cytometry or validated MRD testing
For T-LBL (biopsy proven at current or prior relapse): Radiographically detectable mass or lymph node involvement OR
Relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) with bone marrow involvement ≥1% (assessable by morphology, flow cytometry or validated MRD testing) and at least one of the following characteristics:
First relapse with adverse biologic determinants as described below:
KMT2A rearrangement
Low hypodiploidy, defined as ≤ 40 chromosomes
t(17;19)
IKZF1 deletion (without targetable ABL1 fusion)
Ph-like ALL (without targetable ABL1 fusion)
Other biologic determinants with adverse prognosis in discussion with the Sponsor-Investigator
Early first bone marrow relapse occurring \<36 months from initial diagnosis
Primary refractory ALL that has failed 1 prior induction attempt
Age: ≥ 1 and ≤ 21 years of age
Lansky/Karnofsky performance status ≥ 50%
Participants must have fully recovered from the acute toxic effects of all prior and meet all of the following criteria:
Myelosuppressive chemotherapy: 14 days, or 5 half-lives, whichever is shorter, must have elapsed since the completion of myelosuppressive therapy. Individuals may have received any of the following medications without a...
Standard maintenance therapy: dexamethasone/prednisone, vincristine, 6MP, low dose methotrexate
Hydroxyurea
Intrathecal chemotherapy with methotrexate, hydrocortisone and/or cytarabine.
Radiation therapy (XRT):
Total Body Irradiation (TBI) or cranial radiation therapy: Must have been completed more than 90 days prior to study entry
XRT for chloroma does not require a washout period.
Palliative XRT does not require a washout
Small molecule inhibitors (BCR-ABL or FLT3 inhibitors, for example): 7 days, or 5 half-lifes, whichever is shorter) must have elapsed since the completion of therapy. For agents that have known adverse events occurring...
Immunotherapy: At least 30 days after the administration of any type of immunotherapy, including, but not limited to, tumor vaccines, chimeric antigen receptor (CAR) therapy, other immune effector cell therapy and...
Monoclonal antibodies: At least 3 half-lives of the antibody after the last dose of a monoclonal antibody
Prior hematopoietic stem cell transplant (HSCT): Patients who have received HSCT are eligible, but must meet all of the following conditions:
Allogeneic HSCT \> 90 days of study entry
No evidence of graft-versus-host-disease (GVHD)
Adequate organ function, as defined by the following laboratory values:
Serum alanine aminotransferase (ALT) ≤5X upper limit of normal (ULN), unless deemed secondary to leukemic involvement in discussion with site PI.)
Direct bilirubin ≤ 3X upper limit of normal for age and institution.
Serum amylase ≤ 3X institutional ULN .
Cardiac function as defined as below:
Ejection fraction ≥ 50% or shortening fraction of ≥ 24% on screening echocardiogram.
Maximum prior cumulative doxorubicin dose ≤ 360 mg/m2 or equivalent
Because of the teratogenic effects of venetoclax on developing fetuses, female participants of childbearing potential must have a negative urine or serum HCG prior to study entry and at the start of therapy. All females...

What rules you out

Cohort A Exclusion Criteria
Use of strong or moderate CYP3A inhibitors/inducers within 3 days of study entry
Individuals who have had a stem cell transplant and are still receiving treatment for GVHD or GVHD prophylaxis, or who have evidence of acute GVHD
Individuals with known active hepatitis; baseline testing not required.
Patients with systemic infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment.
Patients known to have human immunodeficiency virus (HIV) infection; baseline testing for HIV is not required.
Pregnant or nursing women are excluded.
Individuals with significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or...
Use of strong or moderate CYP3A inhibitors/inducers within 3 days of study entry
Individuals who have had a stem cell transplant and are still receiving treatment for GVHD or GVHD prophylaxis, or who have evidence of acute GVHD
Individuals with known active hepatitis; baseline testing not required.
Patients with systemic infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment.
Patients known to have human immunodeficiency virus (HIV) infection; baseline testing for HIV is not required.
Pregnant or nursing women are excluded.
Individuals with significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or...
Use of strong or moderate CYP3A inhibitors/inducers within 3 days of study entry
Individuals who have had a stem cell transplant and are still receiving treatment for GVHD or GVHD prophylaxis, or who have evidence of acute GVHD, or who are less than 90 days from stem cell infusion
Individuals with known active hepatitis; baseline testing not required.
Patients with systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment.
Patients known to have human immunodeficiency virus (HIV) infection; baseline testing for HIV is not required.
Pregnant or nursing women are excluded
Individuals with significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or...
Individuals with a history of allergic reactions to any of the agents being used in this trial, with the exception of pegaspargase or calaspargase pegol. Participants with a history of allergy to pegylated formulation...
History of asparaginase-associated pancreatitis.
Known, active and propagating deep venous thrombus (DVT).
Individuals with isolated CNS or testicular relapse.
Presence of surface immunoglobulin by flow cytometry and/or known t(8;14), t(2;8), or t(8;22).
Individuals with a history of a different malignancy are ineligible except for the following circumstances:
Individuals are eligible if they have been disease-free for at least 1 year and are deemed by the investigator to be at low risk for recurrence of that malignancy.
Individuals with the following cancers are eligible if diagnosed and treated within the past year: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.

The study team makes the final eligibility decision.

Where it's taking place

San Francisco, California, United States
Aurora, Colorado, United States
Atlanta, Georgia, United States
Chicago, Illinois, United States
Boston, Massachusetts, United States

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 1 year to 40 years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include San Francisco, California, United States; Aurora, Colorado, United States; Atlanta, Georgia, United States; Chicago, Illinois, United States; Boston, Massachusetts, United States. Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.