Brief Title
Myeloablative Allo HSCT With Related or Unrelated Donor for Heme Disorders
Official Title
Myeloablative Allogeneic Hematopoietic Cell Transplantation Using a Related or Unrelated Donor for the Treatment of Hematological Diseases
Brief Summary
This is a Phase II study of allogeneic hematopoietic stem cell transplant (HCT) using a
myeloablative preparative regimen (of either total body irradiation (TBI); or,
fludarabine/busulfan for patients unable to receive further radiation). followed by a
post-transplant graft-versus-host disease (GVHD) prophylaxis regimen of post-transplant
cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF).
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Chronic GVHD - 1 year
Secondary Outcome
Grade II-IV acute GVHD
Condition
Acute Leukemia
Intervention
HSCT with TBI Regimen
Study Arms / Comparison Groups
TBI Regimen
Description:
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
300
Start Date
March 30, 2018
Completion Date
November 10, 2025
Primary Completion Date
January 10, 2025
Eligibility Criteria
-Inclusion Criteria:
- Age: ≤ 60 years of age
- Performance Status: Karnofsky ≥ 70%, Lansky play score ≥ 70
- Consent: Voluntary written consent (adult or legally authorized representative; or
parental/guardian)
- Adequate Organ Function:
- Renal: Creatinine <2x upper limit of normal. Patients above this limit must have
creatinine clearance ≥ 40 ml/min/1.73m2 as determined by an age-appropriate
method, such as cystatin C GFR.
- Hepatic: Bilirubin, AST, alkaline phosphatase <4 times the upper limit of
institutional normal
- Pulmonary: Diffusion capacity of oxygen, corrected for hemoglobin, > 50% of
predicted. For pediatric patients not able to undergo PFTs or diffusion testing:
O2 sat of >95% on room air
- Cardiac: Absence of decompensated congestive heart failure, or uncontrolled
arrhythmia and left ventricular ejection fraction > 45%. For children not able to
cooperate with MUGA or echocardiography, such should be clearly stated in the
physician's documentation
- HIV Status: 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
Other Inclusion Criteria:
- Women of child bearing potential and sexually active males with partners of child
bearing potential must agree to use adequate birth control for the duration of
treatment.
- Donor Availability: Patients considered for transplantation must have a sufficient
graft as based on current criteria of the University of Minnesota Blood and Marrow
Transplantation Program
- Eligible Diseases and Status: Patients are eligible unless their treatment is to be
guided by a higher priority protocol.
- Acute Leukemias: Must be in remission by morphology (≤5% blasts). Also a small
percentage of blasts that is equivocal between marrow regeneration vs. early relapse
are acceptable provided there are no associated cytogenetic markers consistent with
relapse.
- 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:
- 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
- Normal karyotype with double mutated CEBPA
- Acute prolymphocytic leukemia (APL) in first molecular remission at the end of
consolidation
- 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 lymphoblastic leukemia (ALL)/lymphoma: second or greater CR; 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 achieve 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 one or more
tyrosine kinase inhibitors.
- Plasma Cell Leukemia after initial therapy, in patients who have achieved at least a
partial remission
- Myeloproliferative Neoplasms/Myelofibrosis, either primary as a result of polycythemia
vera or essential thrombocythemia, with disease risk of intermediate or high-risk
according to DIPSS criteria. Blasts must be <10% by bone marrow aspirate morphology.
- Myelodysplasia (MDS) IPSS INT-2 or High Risk (i.e. RAEB, RAEBt) or Refractory Anemia
with severe pancytopenia, transfusion dependence, or high risk cytogenetics or
molecular features. Blasts must be < 10% by a representative 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 debulking chemotherapy before transplant.
- Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia are eligible
after initial therapy in CR1+ or PR1+.
- Diffuse large Cell NHL > CR/> PR: Patients in CR/PR with initial short remission (<6
months) are eligible, or those who have failed/or are not eligible for autologous
transplant.
- 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.
- Juvenile myelomonocytic leukemia
- Biphenotypic/Undifferentiated/Prolymphocytic Leukemias in first or subsequent CR.
- MRD positive leukemia (AML, ALL or accelerated/blast phase CML). Selected patients in
morphologic CR, but with positive immunophenotypic (flow cytometry) or molecular
evidence of MRD may be eligible if recent chemotherapy has not resulted in MRD
negative status.
- Natural Killer Cell Malignancies
- Acquired Bone Marrow Failure Syndromes except for Fanconi Anemia or Dyskeratosis
Congenita
- 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.
Exclusion Criteria:
- Chemotherapy refractory large cell and high grade NHL (i.e., progressive disease after
> 2 salvage regimens)
- CML in blast crisis
- Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressing on
salvage therapy.
- 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.
- Active central nervous system malignancy
- if ≤ 18 years old, prior myeloablative transplant within the last 6 months. If >18
years old prior myeloablative allotransplant or autologous transplant
- Active HIV infection or known HIV positive serology
- active uncontrolled infection
- Pregnant or breastfeeding. 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.
Gender
All
Ages
N/A - 60 Years
Accepts Healthy Volunteers
No
Contacts
Shernan Holtan, MD, (612)-273-2800, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03314974
Organization ID
2015LS034
Secondary IDs
MT2015-29
Responsible Party
Sponsor
Study Sponsor
Masonic Cancer Center, University of Minnesota
Study Sponsor
Shernan Holtan, MD, Principal Investigator, Masonic Cancer Center, University of Minnesota
Verification Date
April 2022