Allo HSCT Using RIC for Hematological Diseases
Allogeneic Hematopoietic Stem Cell Transplantation Using Reduced Intensity Conditioning (RIC) for the Treatment of Hematological Diseases [MT2015-32]
1 other identifier
interventional
156
1 country
1
Brief Summary
This is a phase II trial using a non-myeloablative cyclophosphamide/ fludarabine/total body irradiation (TBI) preparative regimen followed by a related or unrelated donor stem cell infusion. The primary objective is to evaluate rates of acute graft-versus-host disease (GVHD) grades II-IV and chronic GVHD with an updated GVHD prophylaxis of tacrolimus and mycophenolate mofetil (MMF) with a non-myeloablative preparative regimen in persons with hematologic malignancies.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Mar 2017
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 19, 2016
CompletedFirst Posted
Study publicly available on registry
January 21, 2016
CompletedStudy Start
First participant enrolled
March 9, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 17, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
May 29, 2023
CompletedSeptember 21, 2023
September 1, 2023
6.1 years
January 19, 2016
September 19, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Evaluate rates of acute graft-versus-host disease (GVHD) II-IV
Percent of subjects with grade II-IV acute GVHD
Day 100 post transplant
Secondary Outcomes (15)
Evaluate rates of chronic GVHD
1 year post transplant
Evaluate neutrophil engraftment without ATG (in siblings)
Day 42 post transplant
Evaluate neutrophil engraftment with ATG (in unrelated donors)
Day 42 post transplant
Evaluate neutrophil engraftment without ATG (in unrelated donors)
Day 42 post transplant
Evaluate relapse without ATG (in siblings) - 1 year
1 year post transplant
- +10 more secondary outcomes
Study Arms (1)
Reduced Intensity Conditioning
EXPERIMENTALNon-myeloablative cyclophosphamide/ fludarabine/total body irradiation (TBI) preparative regimen followed by a related or unrelated donor stem cell infusion
Interventions
300 mg/day (for peds -150 mg/m\^2/day), day -6 and continue through day 0 or longer if clinically indicated
30 mg/m\^2 IV over 1 hour, day -6, -5, -4, -3 and -2
50 mg/kg IV over 2 hours, day -6
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).
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.
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.
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.
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.
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.
Eligibility Criteria
You may qualify if:
- Age, Performance Status, and Graft 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
- /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+.
- +13 more criteria
You may not qualify if:
- 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 blood test or urine study within 14 days prior to registration to rule out pregnancy.
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, 55455, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Erica Warlick, MD
Masonic Cancer Center, University of Minnesota
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 19, 2016
First Posted
January 21, 2016
Study Start
March 9, 2017
Primary Completion
April 17, 2023
Study Completion
May 29, 2023
Last Updated
September 21, 2023
Record last verified: 2023-09