Acute Myelogenous LeukemiaPhase 2NCT05805605
Allo HSCT Using RIC and PTCy for Hematological Diseases
A Phase 2 study testing Peripheral Blood Stem Cell Transplant, Allopurinol 300 MG and Fludarabine in people with Acute Myelogenous Leukemia and Acute Lymphocytic Leukemia, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial summary
This is a Phase II study following subjects proceeding with our Institutional non-myeloablative cyclophosphamide/ fludarabine/total body irradiation (TBI) preparative regimen followed by a related, unrelated, or partially matched family donor stem cell infusion using post-transplant cyclophosphamide (PTCy), sirolimus… Read more about this study
- Who is it for?
- Ages Up to 75 years
- Conditions the study is for
- Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia, Biphenotypic Acute Leukemia
- What is being tested?
- Peripheral Blood Stem Cell Transplant, Allopurinol 300 MG and Fludarabine
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2023to 22 Oct 2028
- Phase
- Phase 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 Up to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age 0 to 75 years of age with Karnofsky score ≥ 70% (≥ 16 years) or Lansky score ≥ 50 (< 16 years).
- 5/6 or 6/6 related donor, OR a 7-8/8 HLA-A, B, C, DRB1 allele match, OR a haplotype (at least 5/10) matched related donor. Donors will be requested to provide PBSCs although bone marrow is acceptable according to donor preference.
- Eligible Diseases Acute Leukemias: Must be in remission by morphology (≤5% blasts) AND without evidence of MRD by flow cytometry, FISH, or conventional cytogenetics. PCR based MRD detection is not an exclusion to proceed.
- Acute Myeloid Leukemia (AML) and related precursor neoplasms:
- 2nd or greater complete remission (CR); first complete remission (CR1) in patients > 60 years old; CR1 in ≤ 60 years old that is NOT considered as favorable-risk.
- Favorable risk AML is defined as having one of the following:
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- t(8,21) without cKIT mutation
- inv(16) or t(16;16) without cKIT mutation
- Normal karyotype with mutated NPM1 and wild type FLT-ITD (unless persistently NPM1 positive by PCR following two cycles of chemotherapy)
- Normal karyotype with double mutated CEBPA
- Acute prolymphocytic leukemia (APL) in first molecular remission at the end of consolidation
- Acute lymphoblastic Leukemia (ALL) /lymphoma:
- CR2 or greater, CR1 unable to tolerate consolidation chemotherapy due to chemotherapy-related toxicities; CR1 high-risk ALL.
- High risk ALL is defined as having one of the following:
- Evidence of high risk cytogenetics, e.g. t(9;22), t(1;19), t(4;11), other MLL rearrangements, IKZF1
- 30 years of age or older at diagnosis
- White blood cell counts of greater than 30,000/mcL (B-ALL) or greater than 100,000/mcL (T-ALL) at diagnosis
- CNS leukemia involvement during the course of disease
- Slow cytologic response (>10% lymphoblasts in bone marrow on Day 14 of induction therapy)
- Evidence of persistent immonophenotypic or molecular minimal residual disease (MRD) at the end of induction and consolidation therapy.
- Very high risk pediatric patients with ALL:
- patients <21 years are also considered high risk CR1 if they had M2 or M3 marrow at day 42 from the initiation of induction or M3 marrow at the end of induction. They are eligible once they achieved a complete remission.
- Biphenotypic/Undifferentiated/Prolymphocytic Leukemias in first or subsequent CR.
- Chronic Myelogenous Leukemia in chronic or accelerated phase, or CML blast crisis in morphological remission (<5% blasts) and with negative MRD by flow cytometry (a positive PCR for BCRABL is acceptable for BMT): Chronic phase patients must have failed at least two different TKIs, been intolerant to all available TKIs or have T315I mutation. Patients with CML blast crisis in CR are only eligible if there is an feasible TKI maintenance plan following BMT.
- Plasma Cell Leukemia after initial therapy, who achieved at least a partial remission; or relapsed and achieved subsequent remission (CR/PR) Myelodysplastic Syndrome: IPSS INT-2 or High Risk; R-IPSS High or Very High; WHO classification: RAEB-1, RAEB-2; Severe Cytopenias: ANC < 0.8, Anemia or thrombocytopenia requiring transfusion; Poor or very poor risk cytogenetics based on IPSS or R-IPSS definitions; therapy-related MDS. Blasts must be < 5% by bone marrow aspirate morphology. If ≥5% blasts, patient requires chemotherapy for cytoreduction to <5% blasts prior to transplantation Leukemia or MDS in aplasia. These patients may be taken to transplant if after induction therapy they remain with aplastic bone marrow and no morphological or flow-cytometry evidence of disease ≥ 28 days post-therapy. These high risk patients will be analyzed separately.
- Burkitt's Lymphoma in CR2 or subsequent CR. Relapsed T-Cell Lymphoma that is chemotherapy sensitive in CR/PR that has failed or ineligible for an autologous transplantNatural Killer Cell Malignancies. Relapsed Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Marginal Zone B-Cell Lymphoma or Follicular Lymphoma which have progressed within 12 months of achieving a partial or complete remission. Patients who had remissions lasting > 12 months, are eligible after at least two prior therapies. Patients with bulky disease should be considered for de-bulking chemotherapy before transplant. Patients with refractory disease may be eligible, unless bulky disease and an estimated tumor doubling time of less than one month.
- Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphomais eligible after initial therapy if chemotherapy sensitive.
- Large Cell and other high risk NHL > CR2/> PR2: Patients in CR2/PR2 with initial short remission (<6 months) are eligible.
- Relapsed Multiple Myeloma: that is chemotherapy sensitive and has failed or ineligible for an autologous transplant.
- Myeloproliferative Neoplasms/Myelofibrosis - with transfusion dependence or expected survival under 5 years by DIPSS, DIPSS-plus, or MPSS70 calculator.
- Acquired Bone Marrow Failure Syndromes except for Fanconi anemia Other Leukemia Subtypes: A major effort in the field of hematology is to identify patients who are of high risk for treatment failure so that patients can be appropriately stratified to either more (or less) intensive therapy. This effort is continually ongoing and retrospective studies identify new disease features or characteristics that are associated with treatment outcomes. Therefore, if new features are identified after the writing of this protocol, patients can be enrolled with the approval of two members of the study committee.
- Additional Criteria for Bulky Disease (lymphomas) if stable disease is best response, the largest residual nodal mass must < 5 cm (approximately) If response to previous therapy, the largest residual mass must represent a 50% reduction and be < 7.5 cm (approximately)
- Organ Function Criteria
- Adequate organ function is defined as:
- Liver: Transaminases ≤ 5 x upper limit of normal (ULN) and total bilirubin ≤ 2.5 mg/dL except for patients with Gilbert's syndrome or hemolysis.
- Renal: A normal creatinine (adults) or creatinine clearance ≥ 40 mL/min (pediatrics). Adults with a creatinine > 1.2 mg/dl or a history of renal dysfunction must have estimated GFR ≥ 40 ml/min/1.73m2.
- Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction > 40%. For children that are not able to cooperate with MUGA and echocardiography, such should be clearly stated in the physician's note.
- Pulmonary: DLCO, FEV1, FVC ≥ 40% predicted, and absence of O2 requirements. For children that are not able to cooperate with PFTs, a pulse oximetry with exercise should be attempted. If neither test can be obtained it should be clearly stated in the physician's note.
- If recent confirmed mold infection (e.g. aspergillus) must have minimum of 30 days of therapy and responsive disease and be cleared by Infectious Disease HIV infection with undetectable viral load. All HIV+ patients must be evaluated by Infectious Disease (ID) and a HIV management plan establish prior to transplantation Sexually active females of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control during study treatment Voluntary written consent (adult or parent/guardian with presentation of the minor information sheet, if appropriate)
- Related donors will be evaluated and collected according to UMN BMT program standard processes. Unrelated donors will be identified and collected through the National Marrow and Donor Program (NMDP) per usual steps.
Who cannot join
- Pregnant or breast feeding. The agents used in this study include Pregnancy Category D: known to cause harm to a fetus. Females of childbearing potential must have a negative pregnancy test prior to starting therapy.
- Untreated active infection
- Active central nervous system malignancy
- CML in blast crisis
- Intermediate or high grade NHL, mantle cell NHL, and Hodgkin disease that is progressive on salvage therapy. Stable disease is acceptable to move forward provided it is non-bulky.
- Less than 3 months since prior myeloablative transplant
- Evidence of progressive disease by imaging modalities or biopsy - persistent PET activity, though possibly related to lymphoma, is not an exclusion criterion in the absence of CT changes indicating progression.
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
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, 55455
Mark Juckett
About this study
Official title: Allogeneic Hematopoietic Stem Cell Transplantation Using Reduced Intensity Conditioning (RIC) With Post-Transplant Cytoxan (PTCy) for the Treatment of Hematological Diseases
This is a Phase II study following subjects proceeding with our Institutional non-myeloablative cyclophosphamide/ fludarabine/total body irradiation (TBI) preparative regimen followed by a related, unrelated, or partially matched family donor stem cell infusion using post-transplant cyclophosphamide (PTCy), sirolimus and MMF GVHD prophylaxis.
- Conditions
- Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia, Biphenotypic Acute Leukemia, Undifferentiated Leukemia, Prolymphocytic Leukemia, Chronic Myelogenous Leukemia
- Being tested
- Peripheral Blood Stem Cell Transplant, Allopurinol 300 MG, Fludarabine, Cyclophosphamide, Bone Marrow Cell Transplant
- Keywords
- MDS, CLL, SLL, AML, CML, PFS, TRM, GVHD, MMF, TBI, PTCy, ALL
- Medical subject headings
- Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Biphenotypic, Acute, Leukemia, Prolymphocytic, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Plasma Cell, Myelodysplastic Syndromes, Leukemia, Myeloid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Peripheral Blood Stem Cell TransplantBiological
On day 0, a target dose of 5 x 106 CD34 cells/kg will be infused.
Allopurinol 300 MGDrug
300 mg/day from day -7 to day 0. Allopurinol 150mg/m2/day for pediatric participants.
FludarabineDrug
30 mg/m2 IV over 1 hour. Administered on day -6 to day -2.
CyclophosphamideDrug
Administered as a 2 hour IV infusion on day -6, +3, and +4.
Bone Marrow Cell TransplantBiological
On day 0, a target dose of 3 x 108 nucleated cells/kg recipient weight will be infused.
Total Body IrradiationRadiation
The dose of TBI will be 200 cGy given in a single fraction on day -1.
Sirolimus PillDrug
All participants begin +5 to day +60.
Loading dose on day +5 of 5 mg/m2/day orally once (max dose of 8 mg).
Maintenance dose 2.5 mg/m2 orally daily to maintain a level of 8-12 ng/ml (max dose of 4 mg).
Also called (MMF)
All patients begin day +5 through day +35.
3 gram/day IV/PO for patients who are ≥ 40 kg divided in 2 doses. In obese patients (>125% IBW) 15 mg/kg every 12 hours may be considered. Pediatric patients will receive MMF at the dose of 15 mg/kg/dose (maximum of 1 gram per dose) every 8 hours.
| Study group | Role | What they receive |
|---|---|---|
| Cy/Flu/TBI + Post transplant CY | Experimental | Not described Receives: Biological: Peripheral Blood Stem Cell Transplant; Drug: Allopurinol 300 MG; Drug: Fludarabine; Drug: Cyclophosphamide; Biological: Bone Marrow Cell Transplant; Radiation: Total Body Irradiation; Drug: Sirolimus Pill; Drug: Mycophenolate Mofetil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate rates of acute graft-versus-host disease (GVHD)
Number of participants with GVHD grades 2-4 after one year post transplant.
Measured: 12 months
Evaluate rates of chronic graft-versus-host disease (GVHD)
Number of participants with chronic GVHD after one year post transplant.
Measured: 12 months
Secondary outcomes (3)
Observe rates of relapse (RR)
Number of participants that experienced relapse within 100 days of treatment.
Measured: 100 days
Overall Survival (OS)
Observe overall participant survival at Day 100 and at 1 and 3 years
Measured: 72 months
Observe transplant related mortality (TRM)
Number of participants with transplant related mortality within 12 months of treatment.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2023
- Study start1 May 2023
- Primary completion22 Oct 2027 (estimated)
- Study completion22 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myelogenous LeukemiaStudies of the same condition, open and under way.
- 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
- 56 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mark Juckett, Principal investigator, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05805605
- Sponsor's protocol ID
- 2022LS146
- Status last verified
- Jul 2026
- First submitted
- 21 Feb 2023
- Last updated
- 6 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No