Myelodysplastic Syndrome(MDS)Phase 1/2NCT06548230
A Phase 1B/2A Trial of NADUNOLIMAB in Combination With Azacitidine (With/Without Venetoclax) in Patients With Myelodysplastic Syndrome (MDS) and Acute Myelogenous Leukemia (AML)
A Phase 1/2 study testing Nadunolimab, Azacitidine and Venetoclax in people with Myelodysplastic Syndrome(MDS) and Acute Myelogenous Leukemia (AML), run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
To evaluate safety and determine the recommended Phase II dose (RP2D). We hypothesize that targeting leukemia stem/progenitor cells (LSCs) with nadunolimab (IL1RAP antibody) alone or in combination with current therapies of azacitidine (HMA) and venetoclax (Bcl-2 inhibitor), is an effective treatment strategy for… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndrome(MDS), Acute Myelogenous Leukemia (AML)
- What is being tested?
- Nadunolimab, Azacitidine and Venetoclax
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Mar 2025to 1 Dec 2029
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis
- Arm 1: Diagnosis of MDS intermediate/high/very high risk by Revised International Prognostic Scoring System (IPSS-R), Untreated or up to 2 prior treatments.
- Arm 2: Diagnosis of relapsed/refractory AML (per European Leukemia Network 2022) [26] receiving treatment as salvage 1-2. MDS or CMML treated with hypomethylating agent (HMA) therapies who progress to AML and have no available better therapies or are not candidates for available therapies, will be eligible at the time of progression to AML.
- Patients aged ≥18 years
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2
- Temporary prior measures such as apheresis, limited dose cytarabine or use of hydrea while eligibility work-up is being performed are allowed and not counted as a prior salvage
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- In the absence of rapidly progressing disease, the interval from prior treatment to time of initiation of protocol therapy will be at least 2 weeks or at least 5 half-lives (whichever is shorter). The half-life for the therapy in question will be based on published pharmacokinetic literature (abstracts, manuscripts, investigator brochure's, or drug-administration manuals) and will be documented in the protocol eligibility document.
- The toxicity from prior therapy should have resolved to Grade ≤1, however alopecia and sensory neuropathy Grade ≤2 not constituting a safety risk based on investigators judgement is acceptable.
- The use of chemotherapeutic or anti-leukemic agents is not permitted during the study with the following exceptions: (1) intrathecal (IT) therapy for patients with controlled CNS leukemia at the discretion of the PI. (2) Use of 1-2 doses of cytarabine (up to 1.5 g/m2 each dose) for patients with rapidly proliferative disease is allowed up to 7 days before the start of study therapy (7 days washout). Use of hydroxyurea for patients with rapidly proliferative disease is allowed on study and before the start of study therapy and will not require a washout. These medications will be recorded in the case-report form.
- Concurrent therapy for CNS prophylaxis or continuation of therapy for controlled CNS disease is permitted. Patients with a known history of CNS disease must have been treated with CNS directed therapy, have at least 2 consecutive LPs with no evidence of CNS leukemia, and must be clinically stable for at least 4 weeks prior to enrollment and have no ongoing neurological symptoms that in the opinion of the treating physician are related to the CNS disease
- Serum biochemical values with the following limits:
- Patients must have adequate renal function as demonstrated by a creatinine clearance (CrCl) ≥ 40 mL/min calculated by either the Cockcroft-Gault formula, Modification of Diet in Renal Disease (MDRD) eGFR or measured by 24 hours' urine collection. For patients with BMI >23, Adjusted body weight and not Ideal Body Weight is the recommended parameter.
- Direct bilirubin <1.5 x ULN unless considered due to Gilbert's syndrome
- Aspartate aminotransferase or alanine aminotransferase ≤2.0 x ULN (aspartate aminotransferase or alanine aminotransferase ≤3.0 x ULN if deemed related to leukemia by the treating physician)
- White blood cell count <10 x 109/L. Hydroxyurea may be used to reduce the WBC count to < 10x109/L.
- Ability to understand and provide signed informed consent.
- Females must be surgically or biologically sterile or postmenopausal (amenorrheic for at least 12 months) or if of childbearing potential, must have a negative serum or urine pregnancy test within 72 hours before the start of the treatment
- Women of childbearing potential must agree to use an adequate method of contraception during the study and until 4 months after the last treatment. Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 3 months after the last treatment.
Who cannot join
- Patients with any other known concurrent severe and/or uncontrolled medical condition including but not limited to diabetes, cardiovascular disease including hypertension, renal disease, or active uncontrolled infection, which could compromise participation in the study.
- Patients on active antineoplastic or radiation therapy for a concurrent malignancy at the time of screening. Maintenance therapy, hormonal therapy, or steroid therapy for well-controlled malignancy is allowed.
- Prior organ transplantation including allogenic stem-cell transplantation within 3 months prior to planned enrollment, active graft versus host disease (GVHD) >Grade 1 or requiring transplant-related immunosuppression with the exception of low dose cyclosporine and tacrolimus.
- Patients with symptomatic CNS leukemia or patients with poorly controlled CNS leukemia.
- Patients with a known HIV infection that is not well controlled (i.e. any detectable circulating viral load) at the time of enrollment.
- Patients with known positive hepatitis B or C infection by serology, with the exception of those with an undetectable viral load within 3 months (Hepatitis B or C testing is not required prior to study entry). Subjects with serologic evidence of prior vaccination to HBV [i.e., HBs Ag-, and anti-HBs+] may participate.
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- Patients who have had any major surgical procedure within 14 days of Day 1.
- Other severe acute or chronic medical conditions that is active and not well controlled including colitis, inflammatory bowel disease, or psychiatric conditions including active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
- Active and uncontrolled disease (active infection requiring systemic therapy or fever likely secondary to infection within prior 48 hours): prophylactic antibiotics or prolonged course of IV antibiotics for controlled infection are allowed, uncontrolled hypertension despite adequate medical therapy, active and uncontrolled congestive heart failure NYHA class III/IV, clinically significant and uncontrolled arrhythmia, as judged by the treating physician.
- Requirement to use anti-TNF drugs (infliximab, etanercept, adalimumab, certolizumab, golimumab).
- Patients unwilling or unable to comply with the protocol.
- Live vaccination within 28 days from start of therapy
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
Gautam Borthakur, MBBS, 713-563-1586, gborthak@mdanderson.org
About this study
To evaluate safety and determine the recommended Phase II dose (RP2D). We hypothesize that targeting leukemia stem/progenitor cells (LSCs) with nadunolimab (IL1RAP antibody) alone or in combination with current therapies of azacitidine (HMA) and venetoclax (Bcl-2 inhibitor), is an effective treatment strategy for high-risk MDS and AML, and with a clinical trial we will establish the safety and the early efficacy of this approach.
Read the detailed description
Primary Objectives:
To determine the safety and recommended phase 2 dose (RP2D) of nadunolimab in combination with azacitidine in intermediate/high/very high risk MDS (International prognostic scoring system revised/IPSS-R) who are untreated or had up to 2 prior treatments (Arm 1) or in combination with azacitidine and venetoclax in patients with relapsed/refractory AML receiving treatment as first or second salvage (Arm 2).
Secondary Objectives:
To assess the complete remission (CR)+ CR with incomplete count recovery (CRi) + partial remission (PR)+ morphologic leukemia free state (MLFS) rate as per European Leukemia Network 2017 AML response criteria within 6 cycles of treatment initiation in patients with relapsed refractory AML.
To assess Overall Response Rate (ORR) defined as [CR + marrow complete remission (mCR) + partial remission (PR) + CR with partial hematologic recovery (CRh) + hematological improvement (HI)] as per International Working Group 2023 criteria for MDS in patients with intermediate, high, very high risk MDS (IPSS-R) within 6 cycles of treatment initiation.
To determine the duration of response (DOR).
Exploratory Objectives:
To assess effects on exploratory biomarkers, including serum biomarkers, alterations in hematopoietic subpopulations as measured by multicolor flow cytometry and multimodal single cell analysis, and effects on the leukemic cells as assessed by gene panel analysis and/or single cell DNA-analysis. To evaluate exposure by measuring PK. To evaluate immunogenicity by assessing antidrug antibodies (ADA).
- Being tested
- Nadunolimab, Azacitidine, Venetoclax
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NadunolimabDrug
Give by IV
AzacitidineDrug
Given by IV
VenetoclaxDrug
Given by mouth (PO
| Study group | Role | What they receive |
|---|---|---|
| ARM 1: All Patients Cycle 1 | Experimental | Not described Receives: Drug: Nadunolimab |
| ARM 1A: Cycle 2-24 for responder after Cycle 1 Mono | Experimental | Not described Receives: Drug: Nadunolimab; Drug: Azacitidine; Drug: Venetoclax |
| ARM 1B: Cycle 2-24 for non responder after Cycle 1 Combo | Experimental | Not described Receives: Drug: Nadunolimab; Drug: Azacitidine; Drug: Venetoclax |
| ARM 2: Relapsed/refractory AML | Experimental | Not described Receives: Drug: Nadunolimab; Drug: Azacitidine; Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Adverse Events
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Measured: Through study completion; an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2024
- Study start5 Mar 2025
- Primary completion1 Dec 2027 (estimated)
- Study completion1 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic Syndrome(MDS)Studies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gautam Borthakur, MBBS, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06548230
- Sponsor's protocol ID
- 2023-0261
- Other IDs
- NCI-2024-06340
- Status last verified
- Sep 2026
- First submitted
- 6 Aug 2024
- Last updated
- 25 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No