Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE2
156 participants
INTERVENTIONAL
2017-03-09
2023-05-29
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Allo HSCT Using RIC and PTCy for Hematological Diseases
NCT05805605
Reduced Intensity (RIC) Conditioning And Transplantation of HLA-Haplo-HCT
NCT02988466
Reduced-Intensity Conditioning Before Donor Stem Cell Transplant in With High-Risk Hematologic Malignancies
NCT01760655
Haploidentical Donor Bone Marrow Transplant in Treating Patients With High-Risk Hematologic Cancer
NCT00049504
Fludarabine Phosphate and Total-Body Radiation Followed by Donor Peripheral Blood Stem Cell Transplant and Immunosuppression in Treating Patients With Hematologic Malignancies
NCT00014235
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Reduced Intensity Conditioning
Non-myeloablative cyclophosphamide/ fludarabine/total body irradiation (TBI) preparative regimen followed by a related or unrelated donor stem cell infusion
Allopurinol
300 mg/day (for peds -150 mg/m\^2/day), day -6 and continue through day 0 or longer if clinically indicated
Fludarabine
30 mg/m\^2 IV over 1 hour, day -6, -5, -4, -3 and -2
Cyclophosphamide
50 mg/kg IV over 2 hours, day -6
ATG
Only for patients with an unrelated donor (URD) and NO multi-agent chemotherapy 3 months prior to transplant. ATG will be administered IV every 12 hours for 6 doses on days -6, -5, and -4 according to institutional guidelines. Methylprednisolone 1 mg/kg IV administered immediately prior to each dose of ATG (6 doses).
TBI
All patients who have had previous radiation therapy or TBI will be seen by Radiation Oncology prior to entrance on the protocol for approval for additional 200 cGy of TBI. TBI may be delivered by local guidelines provided the effective dose is equivalent to what is recommended in the TBI Guidelines. The dose of TBI will be 200 cGy given in a single fraction on day -1.
Tacrolimus
All patients will receive tacrolimus therapy beginning on day -3. Initial dosing of tacrolimus will be 0.03 - 0.05 mg/kg/day IV; if the recipient body weight is \<40 kg, dosing will be 3 times daily, and if ≥ 40 kg, twice daily or per current institutional guidelines.
An attempt will be made to maintain a trough level of 5-10 ng/mL and subsequent dose modifications will be provided by the pharmacist.
Once the patient can tolerate oral medications and has a reasonable oral intake, tacrolimus will be converted to an oral form based on the current IV dose providing normal renal and hepatic function and no major drug interactions.
The timing of the tacrolimus taper will be at the discretion of the treating physician, but in general:
* Taper begins at day +100 +/- 10 days, if the patient is stably engrafted and has no active GVHD.
* Taper to zero by reducing dose by approximately 10% a week (rounded to nearest pill size), with a goal to discontinue by month 6 post-HCT.
MMF
3 gram/day IV/PO for patients who are ≥ 40 kg divided in 2 or 3 doses. In obese patients (\>125% IBW) 15 mg/kg every 12 hours may be considered. Pediatric patient (\<40 kilograms) will receive MMF at the dose of 15 mg/kg/dose every 8 hours beginning day -3. MMF dosing will be monitored and altered as clinically appropriate based on institutional guidelines. Patients will be eligible for MMF dosing and pharmacokinetics studies.
MMF will stop at day +30 or 7 days after engraftment, whichever day is later, if no acute GVHD. (Definition of engraftment is 1st day of 3 consecutive days of absolute neutrophil count \[ANC) ≥ 0.5 x 109 /L\]). If no donor engraftment, MMF will continue as long as clinically indicated.
Peripheral Blood Stem Cells
On day 0, patients will receive an allogeneic transplant using PBSC which are CD34+ selected as the donor graft. The graft will be infused over 15-60 minutes after premedication with acetaminophen 650 mg PO and diphenhydramine 25 mg PO/IV with doses adjusted for pediatric patients.
Related or Unrelated Bone Marrow Cells
On day 0, a target dose of 3 x 10\^8 nucleated cells/kg recipient weight will be collected. The graft will be infused over 15-60 minutes after premedication with acetaminophen 650 mg PO and diphenhydramine 25 mg PO/IV with doses adjusted for pediatric patients.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Allopurinol
300 mg/day (for peds -150 mg/m\^2/day), day -6 and continue through day 0 or longer if clinically indicated
Fludarabine
30 mg/m\^2 IV over 1 hour, day -6, -5, -4, -3 and -2
Cyclophosphamide
50 mg/kg IV over 2 hours, day -6
ATG
Only for patients with an unrelated donor (URD) and NO multi-agent chemotherapy 3 months prior to transplant. ATG will be administered IV every 12 hours for 6 doses on days -6, -5, and -4 according to institutional guidelines. Methylprednisolone 1 mg/kg IV administered immediately prior to each dose of ATG (6 doses).
TBI
All patients who have had previous radiation therapy or TBI will be seen by Radiation Oncology prior to entrance on the protocol for approval for additional 200 cGy of TBI. TBI may be delivered by local guidelines provided the effective dose is equivalent to what is recommended in the TBI Guidelines. The dose of TBI will be 200 cGy given in a single fraction on day -1.
Tacrolimus
All patients will receive tacrolimus therapy beginning on day -3. Initial dosing of tacrolimus will be 0.03 - 0.05 mg/kg/day IV; if the recipient body weight is \<40 kg, dosing will be 3 times daily, and if ≥ 40 kg, twice daily or per current institutional guidelines.
An attempt will be made to maintain a trough level of 5-10 ng/mL and subsequent dose modifications will be provided by the pharmacist.
Once the patient can tolerate oral medications and has a reasonable oral intake, tacrolimus will be converted to an oral form based on the current IV dose providing normal renal and hepatic function and no major drug interactions.
The timing of the tacrolimus taper will be at the discretion of the treating physician, but in general:
* Taper begins at day +100 +/- 10 days, if the patient is stably engrafted and has no active GVHD.
* Taper to zero by reducing dose by approximately 10% a week (rounded to nearest pill size), with a goal to discontinue by month 6 post-HCT.
MMF
3 gram/day IV/PO for patients who are ≥ 40 kg divided in 2 or 3 doses. In obese patients (\>125% IBW) 15 mg/kg every 12 hours may be considered. Pediatric patient (\<40 kilograms) will receive MMF at the dose of 15 mg/kg/dose every 8 hours beginning day -3. MMF dosing will be monitored and altered as clinically appropriate based on institutional guidelines. Patients will be eligible for MMF dosing and pharmacokinetics studies.
MMF will stop at day +30 or 7 days after engraftment, whichever day is later, if no acute GVHD. (Definition of engraftment is 1st day of 3 consecutive days of absolute neutrophil count \[ANC) ≥ 0.5 x 109 /L\]). If no donor engraftment, MMF will continue as long as clinically indicated.
Peripheral Blood Stem Cells
On day 0, patients will receive an allogeneic transplant using PBSC which are CD34+ selected as the donor graft. The graft will be infused over 15-60 minutes after premedication with acetaminophen 650 mg PO and diphenhydramine 25 mg PO/IV with doses adjusted for pediatric patients.
Related or Unrelated Bone Marrow Cells
On day 0, a target dose of 3 x 10\^8 nucleated cells/kg recipient weight will be collected. The graft will be infused over 15-60 minutes after premedication with acetaminophen 650 mg PO and diphenhydramine 25 mg PO/IV with doses adjusted for pediatric patients.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Age 0 to 70 years of age with Karnofsky score ≥ 70% (≥ 16 years) or Lansky score ≥ 50 (\< 16 years)
* Patients ≥ 70 and ≤ 75 years of age may be eligible if they have a HCT-CI Co-Morbidity score ≤ 2
* Must be ≥ 3 months after prior myeloablative transplant, if applicable
* 5/6 or 6/6 related donor match or a 7-8/8 HLA-A,B,C,DRB1 allele matched unrelated donor marrow and/or PBSC donor match per current institutional guidelines Related donors will be evaluated and collected per MT2012-14C; Unrelated donors will be identified and collected per usual procedures
* Eligible Diseases
* Acute Myeloid Leukemia (AML): high risk CR1 (as evidenced by preceding MDS, high risk cytogenetics, ≥ 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia, FLT-3 ITD +; CR2+. All patients must be in CR as defined by hematological recovery, AND \<5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
* Very high risk pediatric patients with AML: Patients \<21 years, however, are eligible with (M2 marrow) with \< 25% blasts in marrow after having failed one or more cycles of chemotherapy.
* Acute Lymphocytic Leukemia (ALL): factor that define high risk CR1 include but are not limited to cytogenetics demonstrating t(9;22), t (1:19), t(4;11), other MLL rearrangements, hypodiploidy, or IKZF1 abnormalities), DNA index \< 0.81, \> 1 cycle to obtain CR or presence minimal residual disease (MRD). Patients in CR2+ are eligible. All patients must be in CR as defined by hematological recovery, AND \<5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
* 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.
* Chronic Myelogenous Leukemia excluding refractory blast crisis: To be eligible in first chronic phase (CP1) patient must have failed or be intolerant to imatinib mesylate.
* Plasma Cell Leukemia after initial therapy, who achieved at least a partial remission
* Myelodysplasia (MDS) requiring transplant as defined as: 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.
* Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Marginal Zone B-Cell Lymphoma or Follicular Lymphoma are eligible if there was disease progression/relapse within 12 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 (nodal mass greater than 5 cm) should be considered for de-bulking chemotherapy before transplant.
* Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia, NK cell malignancies are eligible after initial therapy in CR1+ or PR1+.
* Large Cell NHL \> CR2/\> PR2: Patients in CR2/PR2 with initial short remission (\<6 months) are eligible.
* Lymphoblastic Lymphoma, Burkitt's Lymphoma, and other high-grade NHL after initial therapy if stage III/IV in CR1/PR1 or after progression if stage I/II \< 1 year.
* Multiple Myeloma beyond PR2: Patients with chromosome 13 abnormalities, first response lasting less than 6 months, or β-2 microglobulin \> 3 mg/L, may be considered for this protocol after initial therapy.
* Myeloproliferative Syndromes
* Organ Function Criteria Adequate organ function is defined as:
* Liver: AST and ALT \< 5 x upper limit of normal and bilirubin \< 3 x upper limit of normal
* Renal: Creatinine ≤ 2.0 mg/dl (adults) and estimated glomerular filtration rate (GFR) ≥ 40 mL/min (pediatrics). Adults with a creatinine \> 1.2 mg/dl or a history of renal dysfunction must have estimated glomerular filtration rate (GFR) \> 40 mL/min.
* Albumin \> 2.5 g/dL
* Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction \> 35%.
* Pulmonary: DLCOcorr ≥ 40% predicted, and absence of O2 requirements. For children that are not able to cooperate with PFTs, a pulse oximetry with or without exercise should be attempted. If neither test can be obtained it should be clearly stated in the physician's note.
* If recent mold infection (e.g. aspergillus) must have minimum of 30 days of therapy and responsive disease and be cleared by Infectious Disease
* Females of child bearing potential and sexually active males 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)
Exclusion Criteria
* Untreated active infection
* Active CNS disease
* Active HIV infection or known HIV positive serology
* Congenital bone marrow failure syndrome
* Previous irradiation that precludes the safe administration of an additional dose of 200 cGy of TBI
* CML in refractory 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.
* Multiple myeloma progressive on salvage chemotherapy
75 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Masonic Cancer Center, University of Minnesota
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Erica Warlick, MD
Role: PRINCIPAL_INVESTIGATOR
Masonic Cancer Center, University of Minnesota
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States
Countries
Review the countries where the study has at least one active or historical site.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2015LS152
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.