Post-transplant Flotetuzumab for AML
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|ClinicalTrials.gov Identifier: NCT05506956|
Recruitment Status : Recruiting
First Posted : August 18, 2022
Last Update Posted : November 3, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Leukemia, Myeloid, Acute||Drug: Flotetuzumab||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||16 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase Ib to Investigate the CD123-targeted DART Flotetuzumab Following Allogeneic Transplant for Patients With CD123+ Acute Myeloid Leukemia|
|Actual Study Start Date :||October 20, 2022|
|Estimated Primary Completion Date :||December 2025|
|Estimated Study Completion Date :||December 2027|
Experimental: Flotetuzumab Following Allogeneic Transplant
All participants will receive one cycle (28 days) of flotetuzumab. After one cycle, all participants will undergo a bone marrow biopsy to assess response and based on the response, may receive additional cycles up to a total cycle of six cycles.
Patients enrolled on dose level 1 (DL1) will receive flotetuzumab by continuous infusion using multi-step lead-in dosing, and then 500 ng/kg/day on days 7-28. After one cycle, all patients will undergo a bone marrow biopsy to assess response including assessment of minimal residual disease (MRD). Patients who fail to achieve a CR, CRi, CRh (complete remission with partial hematologic recovery), or MLFS may continue with subsequent induction cycles as a continuous infusion up to a total of five cycles. If there is evidence of response (CR, CRi, CRh, or MLFS) and the toxicities of treatment are acceptable, patients will be eligible for two consolidation cycles. Additional bone marrow biopsies for response assessment will be performed after the second cycle. If there is a need to de-escalate dosing based on toxicity, then patients will be enrolled on DL-1 using multi-step lead-in dosing, and then 300 ng/kg/day on days 5-28 of the first cycle and days 1-28 of subsequent cycles.
- Maximum tolerated dose (MTD) of flotetuzumab in patients with relapsed/refractory AML following alloHSCT [ Time Frame: 6 months ]Number of participants with dose-limiting toxicities (DLTs) at specified dose levels to determine MTD
- Complete Response to flotetuzumab in patients with relapsed AML following allogeneic hematopoietic stem cell transplant (alloHSCT) [ Time Frame: 6 months ]Number of participants with complete response (CR) following alloHSCT.
- Complete Response with incomplete count recovery to flotetuzumab in patients with relapsed AML following alloHSCT [ Time Frame: 6 months ]Number of participants with complete response with incomplete count recovery (CRi) following allogeneic hematopoietic stem cell transplant (alloHSCT).
- Partial Response to flotetuzumab in patients with relapsed AML following alloHSCT [ Time Frame: 6 months ]Number of participants with partial response (PR) following allogeneic hematopoietic stem cell transplant (alloHSCT).
- Acute graft-versus-host disease (GVHD) incidence [ Time Frame: 6 months ]Number of safety events defined as CTCAE grade III-IV acute GVHD.
- Chronic GVHD incidence [ Time Frame: 6 months ]Number of participants with chronic GVHD requiring systemic immune suppression.
- Non-relapse mortality [ Time Frame: 2 years ]Number of participant deaths without recurrent or progressive disease after allo-HSCT.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- A confirmed prior diagnosis of AML and underwent an alloHSCT as a form of consolidation in a morphologic complete remission
- ECOG performance status 0-2
- Ability to give informed consent
- In agreement to use an effective barrier method of birth control to avoid pregnancy during the study and for a minimum of 30 days after study treatment, for all male and female patients who are fertile
- Age ≥18 years
- Prior treatment with a CD123-targeted therapy will be allowed assuming the patient did not have a grade 3 or 4 adverse reaction to prior use of this treatment
- Normal thyroid function (defined by either a thyroid-stimulating hormone (TSH) within the reference range, a TSH above the reference range with a free T4 within the reference range, or a TSH below the reference range with both a free T4 and total T3 within the reference range) or normal thyroid tests on supplementation or treatment (defined as a TSH within the reference range)
- Patients should be at least 30 days from transplant with morphologic evidence of disease progression on bone marrow biopsy
- The presence of a CD123+ AML must be confirmed by flow cytometry with >1% CD123 AML blasts
- Peripheral blast count ≤20,000/mm3 at time of initiation on Cycle 1 Day 1
- No evidence of donor engraftment (100% patient DNA in bone marrow or peripheral blood after alloHSCT based on either an unsorted specimen or CD3 sorted).
- Active AML in central nervous system (CNS) or testes
- Patients with active, uncontrolled infection. If an infection is controlled and under treatment, then the patient may become eligible.
- Patients with active acute or chronic GVHD requiring GVHD therapy (mycophenolate mofetil, tacrolimus, sirolimus, or steroids) within 30 days
- Patients without active acute or chronic GVHD requiring prophylactic GVHD therapy (mycophenolate mofetil, tacrolimus, sirolimus, or steroids) within 30 days
Inadequate end organ function defined as:
- Hepatic-AST, ALT, and alkaline phosphatase > 3.5X upper limit of normal (ULN), bilirubin >2.5X ULN
- Renal-creatinine clearance <60 mL/min using the modified Cockcroft-Gault formula
- Cardiac-Recent myocardial infarction within 6 months, Congestive Heart Failure with ejection fraction (EF) <50%, active pericarditis or myocarditis
- Pulmonary-Need for supplemental oxygen to maintain oxygen saturation >92%
- Adrenal-Adrenal insufficiency requiring physiologically-dosed steroids
- Women who are pregnant or lactating
- Previous or known hypersensitivity to biological agents or constituents of flotetuzumab or its source material
- Concurrent use of any other investigational drugs
- Uncontrolled infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus or hepatitis C virus (HCV)
- Any active untreated autoimmune disorders (with the exception of vitiligo, resolved childhood atopic dermatitis, prior Grave's disease now euthyroid clinically with stable supplementation)
- Previous treatment with radiotherapy or an immunotherapeutic agent in the 14 days prior to study drug administration (Cycle 1 Day 1) or 5 half-lifes, whichever is longer
- Requirement, at the time of study entry, for concurrent steroids > 10 mg/day of oral prednisone or equivalent, except steroid inhaler, nasal spray, or ophthalmic solution
- Use of granulocyte colony stimulating or granulocyte-macrophage colony stimulating factor in the 2 weeks prior to study drug administration
- Prior adverse event with CD123 therapy necessitating therapy discontinuation
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05506956
|Contact: Jonathan Webster, MDemail@example.com|
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Recruiting|
|Baltimore, Maryland, United States, 21231|
|Contact: Jonathan Webster, MD 410-614-9106 firstname.lastname@example.org|
|Contact: Lisa Zozzaro, RN 443-287-0005 email@example.com|
|Principal Investigator:||Jonathan Webster, MD||Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Responsible Party:||Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Other Study ID Numbers:||
IRB00235421 ( Other Identifier: JHMIRB )
P01CA015396 ( U.S. NIH Grant/Contract )
|First Posted:||August 18, 2022 Key Record Dates|
|Last Update Posted:||November 3, 2022|
|Last Verified:||August 2022|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type