High Risk Myelodysplastic SyndromePhase 2NCT03067571
Daratumumab in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
A Phase 2 study testing Daratumumab in people with High Risk Myelodysplastic Syndrome and Recurrent Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase II trial studies how well daratumumab works in treating patients with acute myeloid leukemia that has come back or does not respond to treatment or high-risk myelodysplastic syndrome. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- High Risk Myelodysplastic Syndrome, Recurrent Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia
- What is being tested?
- Daratumumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Oct 2017to 21 Nov 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Understand and voluntarily sign an informed consent form
- Age >/=18 years at the time of signing the informed consent form
- Diagnosis of AML [other than acute promyelocytic leukemia (APL)] with refractory/relapsed disease; patients with relapsed/refractory high-risk [(intermediate-2 or higher by International Prognostic Scoring System (IPSS) and/or >/= 10% blasts)] MDS will also be eligible. (Treatment approach for relapsed/refractory AML is very similar to that of high risk MDS), or diagnosis of relapsed/refractory T-ALL/T-LBL.
- All non-hematological toxicity of previous cancer therapy should have resolved to =< grade 1 (except alopecia or other toxicities not involving major organs)
- Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 at study entry
- Serum creatinine </= 2 mg/dL and estimated glomerular filtration rate or creatinine clearance >/= 40 ml/min
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- Total bilirubin =< 2 mg/dL
- Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN)
- Women of childbearing potential must be practicing a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies: eg, established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device or intrauterine system; barrier methods: condom with spermicidal foam/gel/film/cream/suppository or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; male partner sterilization (the vasectomized partner should be the sole partner for that subject); true abstinence (when this is in line with the preferred and usual lifestyle of the subject) during and after the study (3 months after the last dose of daratumumab for women)
- A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control eg, either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the study and for 3 months after receiving the last dose of study drug
- AML relapse > 6 months since autologous or allogeneic stem cell transplantation, provided there is no active graft-versus-host disease (GVHD) > grade 1; no treatment with high dose steroids for GVHD (up to 20 mg prednisolone or equivalent); no treatment with immunosuppressive drugs with the exception of low dose cyclosporine and tacrolimus (blood levels of 0.5-0.6 ug/mL)
Who cannot join
- White blood cell count more than 25 × 109 /L prior to initiation of venetoclax
- Pregnant or breast feeding females
- Cancer chemotherapy within 2 weeks prior to start of daratumumab treatment (exception hydroxyurea). Use of hydroxyurea to control proliferative disease will be allowed prior to starting therapy on study and for 7 days during cycle 1-3 (maximum daily dose of 7 gm)
- Subject has received daratumumab or other anti-CD38 therapies previously
- Subject has received a cumulative dose of corticosteroids more than the equivalent of >= 140 mg of prednisone within the 2 week period before cycle 1, day 1
- Subject has known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) < 50% of predicted normal. NOTE: FEV1 testing is required for patients suspected of having COPD and subjects must be excluded if FEV1 < 50% of predicted normal
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- Subject has a history of another malignancy within 5 years before cycle 1, day 1 (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the IND office and supporter's medical monitor, is considered cured with minimal risk of recurrence)
- Subject is known to be seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti- HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR
- Subjects who are seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy) will be excluded.
- Subject has clinically significant cardiac disease, including: myocardial infarction within 1 year before Cycle 1, Day 1, or unstable or uncontrolled disease/condition related to or affecting cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV); cardiac arrhythmia (Common Terminology Criteria for Adverse Events [CTCAE] version 4.03 grade 2 or higher) or clinically significant electrocardiogram (ECG) abnormalities; screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) > 470 msec
- Subject has known severe allergies, hypersensitivity, or intolerance to monoclonal antibodies or human proteins, or their excipients (refer to the latest version of the Investigator Brochure), or known sensitivity to mammalian-derived products
- Subject has any concurrent medical condition or disease (eg, active systemic infection, laboratory abnormalities) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study
- Exclude patients with known Kell antibodies
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-Label, Phase 2 Trial Evaluating the Efficacy and Safety of Daratumumab in Subjects With Relapsed/Refractory Acute Myelogenous Leukemia or High-Risk Myelodysplastic Syndrome
This phase II trial studies how well daratumumab works in treating patients with acute myeloid leukemia that has come back or does not respond to treatment or high-risk myelodysplastic syndrome. Immunotherapy with monoclonal antibodies, such as daratumumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Read the detailed description
The goal of this clinical research study is to learn if daratumumab in combination with venetoclax can help to control acute myelogenous leukemia (AML), high-risk myelodysplastic syndrome (MDS) that is refractory (does not respond to treatment) or relapsed (comes back after being treated), or relapsed/refractory T acute lymphoblastic leukemia/lymphoma (T-ALL, T-LBL) .
OUTLINE:
Patients receive daratumumab intravenously (IV) over 3.25-6.5 hours on days 1, 8, 15 and 22 of cycles 1-2, on days 1 and 15 of cycles 3-6, and on day 1 of subsequent cycles. Cycles repeat every 28 days.
After completion of study treatment, patients are followed up monthly for 1 year, every 6 months for 1 year, and then annually thereafter.
- Conditions
- High Risk Myelodysplastic Syndrome, Recurrent Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia
- Being tested
- Daratumumab
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DaratumumabBiological
Also called Anti-CD38 Monoclonal Antibody, Darzalex, HuMax-CD38, JNJ-54767414
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (daratumumab) | Experimental | Patients receive daratumumab IV over 3.25-6.5 hours on days 1, 8, 15 and 22 of cycles 1-2, on days 1 and 15 of cycles 3-6, and on day 1 of subsequent cycles. Cycles repeat every 28 days. Receives: Biological: Daratumumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Participants With a Response
Response rate as determined by the International Working Group recommendations. Complete remission (CR): The patient must be free of all symptoms related to leukemia and have an absolute neutrophil count >/= 1.0 x 109/L, platelet count >/- 100 x 109/L, and normal bone marrow differential (</= 5% blasts). Complete remission without platelet recovery (CRp): As per CR but platelet count < 100 x 109/L. Partial remission (PR): CR with 6 to 25% abnormal cells in the marrow or 50% decrease in bone marrow blasts. Marrow CR: Bone marrow: </= 5% myeloblasts and decrease by >/= 50% over pre-treatment (MDS only). Morphologic leukemia-free state: Normal marrow differential (<5% blasts); absolute neutrophil count and platelet counts are not considered. (AML only). Hematologic Improvement (HI): HI should be described by the number of individual, positively affected cell lines
Measured: Up to 5 years
Secondary outcomes (3)
Time on Treatment
Time from date of start of study medication until date of off study.
Measured: Up to 5 years
Overall Survival
Time from date of treatment start until date of death due to any cause or last Follow-up.
Measured: Up to 5 years
Progression Free Survival
Time from date of treatment start until the date of first objective documentation of disease-relapse.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2017
- Study start27 Oct 2017
- Primary completion21 Nov 2022
- Study completion21 Nov 2022
Why it stopped: Study terminated early because of lack of efficacy
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for High Risk Myelodysplastic SyndromeStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Gautam Borthakur, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03067571
- Sponsor's protocol ID
- 2016-0889
- Other IDs
- NCI-2018-01222, 2016-0889
- Status last verified
- Sep 2023
- First submitted
- 24 Feb 2017
- Last updated
- 21 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Phase 2 Trial Evaluating the Efficacy and Safety of Daratumumab in Subjects With Relapsed/Refractory Acute Myelogenous Leukemia or High-Risk Myelodysplastic Syndrome
- ClinicalTrials.gov ID
- NCT03067571
- Acronym / sponsor ID
- 2016-0889
- Conditions
- High Risk Myelodysplastic Syndrome, Recurrent Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study terminated early because of lack of efficacy
- Enrolment
- 7 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 27 Oct 2017 (actual)
- Primary completion
- 21 Nov 2022 (actual)
- Study completion
- 21 Nov 2022 (actual)
- First posted
- 1 Mar 2017 (actual)
- Results
- Posted 21 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well daratumumab works in treating patients with acute myeloid leukemia that has come back or does not respond to treatment or high-risk myelodysplastic syndrome. Immunotherapy with monoclonal antibodies, such as daratumumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Detailed description
The goal of this clinical research study is to learn if daratumumab in combination with venetoclax can help to control acute myelogenous leukemia (AML), high-risk myelodysplastic syndrome (MDS) that is refractory (does not respond to treatment) or relapsed (comes back after being treated), or relapsed/refractory T acute lymphoblastic leukemia/lymphoma (T-ALL, T-LBL) .
OUTLINE:
Patients receive daratumumab intravenously (IV) over 3.25-6.5 hours on days 1, 8, 15 and 22 of cycles 1-2, on days 1 and 15 of cycles 3-6, and on day 1 of subsequent cycles. Cycles repeat every 28 days.
After completion of study treatment, patients are followed up monthly for 1 year, every 6 months for 1 year, and then annually thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (daratumumab) | Experimental | Biological: DaratumumabPatients receive daratumumab IV over 3.25-6.5 hours on days 1, 8, 15 and 22 of cycles 1-2, on days 1 and 15 of cycles 3-6, and on day 1 of subsequent cycles. Cycles repeat every 28 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Understand and voluntarily sign an informed consent form
- Age >/=18 years at the time of signing the informed consent form
- Diagnosis of AML [other than acute promyelocytic leukemia (APL)] with refractory/relapsed disease; patients with relapsed/refractory high-risk [(intermediate-2 or higher by International Prognostic Scoring System (IPSS) and/or >/= 10% blasts)] MDS will also be eligible. (Treatment approach for relapsed/refractory AML is very similar to that of high risk MDS), or diagnosis of relapsed/refractory T-ALL/T-LBL.
- All non-hematological toxicity of previous cancer therapy should have resolved to =< grade 1 (except alopecia or other toxicities not involving major organs)
- Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 at study entry
Key exclusion criteria (13 listed)
- White blood cell count more than 25 × 109 /L prior to initiation of venetoclax
- Pregnant or breast feeding females
- Cancer chemotherapy within 2 weeks prior to start of daratumumab treatment (exception hydroxyurea). Use of hydroxyurea to control proliferative disease will be allowed prior to starting therapy on study and for 7 days during cycle 1-3 (maximum daily dose of 7 gm)
- Subject has received daratumumab or other anti-CD38 therapies previously
- Subject has received a cumulative dose of corticosteroids more than the equivalent of >= 140 mg of prednisone within the 2 week period before cycle 1, day 1
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DaratumumabAlso: Anti-CD38 Monoclonal Antibody, Darzalex, HuMax-CD38, JNJ-54767414Given IV | Biological | Treatment (daratumumab) |
Primary outcome
Participants With a Response
Time frame: Up to 5 years
Response rate as determined by the International Working Group recommendations. Complete remission (CR): The patient must be free of all symptoms related to leukemia and have an absolute neutrophil count >/= 1.0 x 109/L, platelet count >/- 100 x 109/L, and normal bone marrow differential (</= 5% blasts). Complete remission without platelet recovery (CRp): As per CR but platelet count < 100 x 109/L. Partial remission (PR): CR with 6 to 25% abnormal cells in the marrow or 50% decrease in bone marrow blasts. Marrow CR: Bone marrow: </= 5% myeloblasts and decrease by >/= 50% over pre-treatment (MDS only). Morphologic leukemia-free state: Normal marrow differential (<5% blasts); absolute neutrophil count and platelet counts are not considered. (AML only). Hematologic Improvement (HI): HI should be described by the number of individual, positively affected cell lines
3 secondary outcomes
Time on Treatment
Time frame: Up to 5 years
Overall Survival
Time frame: Up to 5 years
Progression Free Survival
Time frame: Up to 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Active, not recruitingPhase 1/2
Omacetaxine + Azacitidine in Untreated Patients With High Grade MDS
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Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome
RecruitingPhase 1
First-in-human (FIH) Trial of GEN3018 in Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML) or Higher-risk Myelodysplastic Syndrome (HR-MDS)
R/R AML, R/R HR-MDS
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gautam Borthakur principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Daratumumab in people with High Risk Myelodysplastic Syndrome and Recurrent Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Participants With a Response (time frame: Up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2023.