Donor Stem Cell Transplant in Treating Patients with Blood Cancer

Status: Active

Description

This phase II trial studies how well donor stem cell transplant works in treating patients with blood cancer. Giving total-body irradiation before a donor transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Giving cyclophosphamide, tacrolimus, and mycophenolate mofetil after the transplant may stop this from happening.

Eligibility Criteria

Inclusion Criteria

  • 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); however, a small percentage of blasts that is equivocal between marrow regeneration vs. early relapse are acceptable; minimal residual disease as detected by flow cytometry or molecular methods is allowed, however every reasonable effort (balancing the potential risks and toxicities of additional chemotherapy) should be made to reduce the disease burden to its lowest possible level prior to transplant
  • 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-cell [B]-ALL) or greater than 100,000/mcL (T-cell [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 immunophenotypic 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 Dynamic International Prognostic Scoring System (DIPSS) criteria; blasts must be < 10% by bone marrow aspirate morphology
  • Myelodysplasia (MDS) IPSS intermediate (INT)-2 or high risk (i.e. refractory anemia with excess blasts [RAEB], refractory anemia with excess blasts in transformation [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 first partial remission (PR1+)
  • Diffuse large cell non-Hodgkin lymphoma (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 beta-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 chronic myeloid leukemia [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
  • Related donors that are matched at HLA 7-8/8 loci (HLA A, B, C, and DRB1 loci) by intermediate resolution
  • Unrelated donors that are matched at HLA 8/8 (HLA A, B, C, and DRB1 loci); 1 allele/antigen mismatch at HLA-A, -B, -C, or DRB1 may be considered if no other suitable donor available
  • Both granulocyte-colony stimulating factor (G-CSF) stimulated peripheral blood grafts and bone marrow grafts will be the priority, although bone marrow graft source will be allowed based upon donor preference
  • Karnofsky >= 80%, Lansky play score >= 70
  • Voluntary written consent (adult or legally authorized representative; or parental/guardian)
  • Creatinine =< 2.0 mg/dl (adults) and creatinine clearance >= 40 mL/min (pediatrics); adults with a creatinine > 1.2 mg/dl or a history of renal dysfunction must have estimated creatinine clearance >= 40 ml/min/1.73 m^2
  • Bilirubin < 4 times the upper limit of institutional normal
  • Aspartate aminotransferase (AST) < 4 times the upper limit of institutional normal
  • Alkaline phosphatase < 4 times the upper limit of institutional normal
  • Diffusion capacity of oxygen, corrected for hemoglobin, > 50% of predicted
  • Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction > 45%; for children not able to cooperate with multigated acquisition (MUGA) or echocardiography, such should be clearly stated in the physician’s documentation

Exclusion Criteria

  • Patients considered for transplantation must have a sufficient graft as based on current criteria of the University of Minnesota Blood and Marrow Transplantation Program
  • Related donors will be assessed and collected through University of Minnesota BMT protocol MT2012-14C: “Procedure Guidelines For Related Hematopoietic Stem Cell Donors.”
  • 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 positron emission tomography (PET) activity, though possibly related to lymphoma, is not an exclusion criterion in the absence of computed tomography (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 human immunodeficiency virus (HIV) infection or known HIV positive serology
  • Active uncontrolled infection
  • Pregnant or breastfeeding; females of childbearing potential must have a negative pregnancy test prior to starting therapy

Locations & Contacts

Minnesota

Minneapolis
University of Minnesota / Masonic Cancer Center
Status: Active
Contact: Shernan Grace Holtan
Phone: 612-301-1095
Email: sgholtan@umn.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine whether a graft-versus-host disease (GVHD) prophylaxis regimen of post-transplant cyclophosphamide, tacrolimus and mycophenolate mofetil (MMF) will reduce the likelihood of chronic GVHD in patients receiving a standard hematopoietic myeloablative stem cell transplant.

OUTLINE:

Patients undergo total body irradiation (TBI) on days -5 to -2 and then undergo stem cell transplant on day 0. Patients that are not able to undergo TBI, receive busulfan intravenously (IV) over 3 hours and fludarabine IV over 1 hour on days -5 to -2.

GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 1-2 hours on days 3 and 4, tacrolimus IV or orally (PO) twice daily (BID) or thrice daily (TID) on day 5 until taper day 100, and mycophenolate mofetil IV or PO TID on days 5-35.

After completion of study treatment, patients are followed up for 2 years.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
University of Minnesota / Masonic Cancer Center

Principal Investigator
Shernan Grace Holtan

Trial IDs

Primary ID 2015LS034
Secondary IDs NCI-2017-02310, MT2015-29
Clinicaltrials.gov ID NCT03314974