Recruitment

Recruitment Status
Recruiting

Inclusion Criteria

UCB graft selected according to current University of Minnesota umbilical cord blood graft selection algorithm
Chronic myelogenous leukemia in chronic or accelerated phase, or CML blast crisis in morphological remission (<5% blasts): Chronic phase patients must have failed at least two tyrosine kinase inhibitors, been intolerant to all available TKIs, or have T315I mutation.
Acute prolymphocytic leukemia (APL) in first molecular remission at the end of consolidation
...
UCB graft selected according to current University of Minnesota umbilical cord blood graft selection algorithm
Chronic myelogenous leukemia in chronic or accelerated phase, or CML blast crisis in morphological remission (<5% blasts): Chronic phase patients must have failed at least two tyrosine kinase inhibitors, been intolerant to all available TKIs, or have T315I mutation.
Acute prolymphocytic leukemia (APL) in first molecular remission at the end of consolidation
Relapsed Multiple Myeloma that is chemotherapy sensitive and has failed or ineligible for an autologous transplant.
White blood cell counts of greater than 30,000/mcL (B-ALL) or greater than 100,000/mcL (T-ALL) at diagnosis
Plasma Cell Leukemia after initial therapy if achieved at least in partial remission; or relapsed and achieved subsequent remission (CR/PR)
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.
Burkitt's lymphoma in CR2 or subsequent CR
Myeloproliferative Neoplasms/Myelofibrosis
CNS leukemia involvement during the course of disease
Organ Function Criteria
30 years of age or older at diagnosis
Normal karyotype with mutated NPM1 and wild type FLT-ITD
If response to previous therapy, the largest residual mass must represent a 50% reduction and be < 7.5 cm (approximately)
Biphenotypic/Undifferentiated/Prolymphocytic Leukemias in first or subsequent CR
Evidence of high risk cytogenetics, e.g. t(9;22), t(1;19), t(4;11), other MLL rearrangements, IKZF1
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.
Slow cytologic response (>10% lymphoblasts in bone marrow on Day 14 of induction therapy)
t(8,21) without cKIT mutation
inv(16) or t(16;16) without cKIT mutation
Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are eligible after initial therapy if chemotherapy sensitive.
Karnofsky score ≥ 70% (≥ 16 years) or Lansky score ≥ 50 (< 16 years)
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.
Relapsed Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma, 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 debulking chemotherapy before transplant. Patients with refractory disease are eligible, unless bulky disease and an estimated tumor doubling time of less than one month.
Normal karyotype with double mutated CEBPA
Evidence of persistent immonophenotypic or molecular minimal residual disease (MRD) at the end of induction and consolidation therapy
Large-cell lymphoma, Hodgkin lymphoma and multiple myeloma with chemotherapy sensitive disease who are ineligible for an autologous transplant.
Acquired Bone marrow failure syndromes, except for Fanconi anemia
If stable disease is best response, the largest residual nodal mass must < 5 cm (approximately)
Relapsed T-Cell Lymphoma that is chemotherapy sensitive in CR/PR that has failed or ineligible for an autologous transplant.
Natural killer cell malignancies
<70 years of age with no matched 5/6 or 6/6 sibling donor - patients ≥ 70 and ≤ 75 years of age may be eligible if they have a Co-Morbidity score ≤ 2 (http://www.qxmd.com/calculate-online/hematology/hct-ci)

Exclusion Criteria

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.
Active central nervous system malignancy
...
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.
Active central nervous system malignancy
Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressing on salvage therapy.
CML in blast crisis
Untreated active infection
Active HIV infection or known HIV positive serology
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.

Summary

Conditions
  • Acute Leukemia
  • Acute Lymphoblastic Leukemia/Lymphoma
  • Acute Myeloid Leukemia
  • Biphenotypic/Undifferentiated/Prolymphocytic Leukemias
  • Relapsed Small Lymphocytic Lymphoma
  • Relapsed T-Cell Lymphoma
  • Bone Marrow Failure Syndromes
  • Lymphoplasmacytic Lymphoma
  • Burkitt's Lymphoma
  • Myeloproliferative Neoplasms/Myelofibrosis
  • Natural Killer Cell Malignancies
  • Marginal Zone B Cell Lymphoma
  • Chronic Myelogenous Leukemia
  • Follicular Lymphoma
  • Myelodysplastic Syndrome
  • Relapsed Multiple Myeloma
  • Hodgkin Lymphoma
  • Multiple Myeloma
  • Large Cell Lymphoma
  • Leukemia or MDS in Aplasia
  • Mantle Cell Lymphoma
  • Plasma Cell Leukemia
  • MRD Positive Leukemia
  • Prolymphocytic Leukemia
  • Relapsed Chronic Lymphocytic Leukemia
Type
Interventional
Phase
Phase 2
Design
  • Allocation: Non-Randomized
  • Intervention Model: Parallel Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Younger than 75 years
Gender
Both males and females

Inclusion Criteria

UCB graft selected according to current University of Minnesota umbilical cord blood graft selection algorithm
Chronic myelogenous leukemia in chronic or accelerated phase, or CML blast crisis in morphological remission (<5% blasts): Chronic phase patients must have failed at least two tyrosine kinase inhibitors, been intolerant to all available TKIs, or have T315I mutation.
Acute prolymphocytic leukemia (APL) in first molecular remission at the end of consolidation
...
UCB graft selected according to current University of Minnesota umbilical cord blood graft selection algorithm
Chronic myelogenous leukemia in chronic or accelerated phase, or CML blast crisis in morphological remission (<5% blasts): Chronic phase patients must have failed at least two tyrosine kinase inhibitors, been intolerant to all available TKIs, or have T315I mutation.
Acute prolymphocytic leukemia (APL) in first molecular remission at the end of consolidation
Relapsed Multiple Myeloma that is chemotherapy sensitive and has failed or ineligible for an autologous transplant.
White blood cell counts of greater than 30,000/mcL (B-ALL) or greater than 100,000/mcL (T-ALL) at diagnosis
Plasma Cell Leukemia after initial therapy if achieved at least in partial remission; or relapsed and achieved subsequent remission (CR/PR)
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.
Burkitt's lymphoma in CR2 or subsequent CR
Myeloproliferative Neoplasms/Myelofibrosis
CNS leukemia involvement during the course of disease
Organ Function Criteria
30 years of age or older at diagnosis
Normal karyotype with mutated NPM1 and wild type FLT-ITD
If response to previous therapy, the largest residual mass must represent a 50% reduction and be < 7.5 cm (approximately)
Biphenotypic/Undifferentiated/Prolymphocytic Leukemias in first or subsequent CR
Evidence of high risk cytogenetics, e.g. t(9;22), t(1;19), t(4;11), other MLL rearrangements, IKZF1
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.
Slow cytologic response (>10% lymphoblasts in bone marrow on Day 14 of induction therapy)
t(8,21) without cKIT mutation
inv(16) or t(16;16) without cKIT mutation
Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are eligible after initial therapy if chemotherapy sensitive.
Karnofsky score ≥ 70% (≥ 16 years) or Lansky score ≥ 50 (< 16 years)
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.
Relapsed Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma, 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 debulking chemotherapy before transplant. Patients with refractory disease are eligible, unless bulky disease and an estimated tumor doubling time of less than one month.
Normal karyotype with double mutated CEBPA
Evidence of persistent immonophenotypic or molecular minimal residual disease (MRD) at the end of induction and consolidation therapy
Large-cell lymphoma, Hodgkin lymphoma and multiple myeloma with chemotherapy sensitive disease who are ineligible for an autologous transplant.
Acquired Bone marrow failure syndromes, except for Fanconi anemia
If stable disease is best response, the largest residual nodal mass must < 5 cm (approximately)
Relapsed T-Cell Lymphoma that is chemotherapy sensitive in CR/PR that has failed or ineligible for an autologous transplant.
Natural killer cell malignancies
<70 years of age with no matched 5/6 or 6/6 sibling donor - patients ≥ 70 and ≤ 75 years of age may be eligible if they have a Co-Morbidity score ≤ 2 (http://www.qxmd.com/calculate-online/hematology/hct-ci)

Exclusion Criteria

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.
Active central nervous system malignancy
...
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.
Active central nervous system malignancy
Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressing on salvage therapy.
CML in blast crisis
Untreated active infection
Active HIV infection or known HIV positive serology
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.

Locations

Minneapolis, Minnesota, 55455
Minneapolis, Minnesota, 55455

Tracking Information

NCT #
NCT02722668
Collaborators
Not Provided
Investigators
  • Principal Investigator: Claudio Brunstein, MD, PhD University of Minnesota
  • Claudio Brunstein, MD, PhD University of Minnesota