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CompletedNCT02661035Updated Sep 21, 2023

Allo HSCT Using RIC for Hematological Diseases

A Phase 2 interventional study of Allopurinol and Fludarabine in Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia and Chronic Myelogenous Leukemia, sponsored by Masonic Cancer Center, University of Minnesota. Completed at 1 site in United States. Open to participants aged Up to 75 Years. Per ClinicalTrials.gov, last updated 2023-09-21.

Sponsored by Masonic Cancer Center, University of Minnesota · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
156
Allocation
Not applicable
Ages
Up to 75 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Acute Myelogenous Leukemia
  • Acute Lymphocytic Leukemia
  • Chronic Myelogenous Leukemia
  • Plasma Cell Leukemia
  • Myelodysplastic Syndromes
  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
  • B-Cell Lymphoma
  • Follicular Lymphoma
  • Lymphoplasmacytic Lymphoma
  • Mantle-Cell Lymphoma
  • Prolymphocytic Leukemia
  • Lymphoblastic Lymphoma
  • Burkitt's Lymphoma
  • Non-Hodgkin's Lymphoma
  • Multiple Myeloma
  • Myeloproliferative Syndromes
  • Hematological Diseases

Keywords

  • AML
  • ALL
  • CML
  • MDS
  • CLL
  • SLL
  • NHL
03

In context

Burkitt Lymphoma

392 studies on the registry are indexed under Burkitt Lymphoma; 114 are open to participants now.

This study's enrollment of 156 is above the median of 41 across 354 interventional studies indexed under Burkitt Lymphoma.

Browse Burkitt Lymphoma studies →

Lead sponsor

Masonic Cancer Center, University of Minnesota is the lead sponsor of 284 studies on the registry; 34 are open to participants now.

Of its 39 completed or terminated interventional studies of FDA-regulated products, 28 (72%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
Up to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 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
    • 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

Exclusion Criteria:

  • 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
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
156 participants (actual)

Study arms

  • Experimental
    Reduced Intensity Conditioning

    Non-myeloablative cyclophosphamide/ fludarabine/total body irradiation (TBI) preparative regimen followed by a related or unrelated donor stem cell infusion

    Drug: Allopurinol · Drug: Fludarabine · Drug: Cyclophosphamide · Drug: ATG · Radiation: TBI · Drug: Tacrolimus · Drug: MMF · Biological: Peripheral Blood Stem Cells · Biological: Related or Unrelated Bone Marrow Cells

Interventions

  • DrugAllopurinol

    300 mg/day (for peds -150 mg/m\^2/day), day -6 and continue through day 0 or longer if clinically indicated

    Also known as: Zyloprim

  • DrugFludarabine

    30 mg/m\^2 IV over 1 hour, day -6, -5, -4, -3 and -2

    Also known as: Fludara

  • DrugCyclophosphamide

    50 mg/kg IV over 2 hours, day -6

    Also known as: Cytoxan

  • DrugATG

    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).

    Also known as: Anti-thymocyte globulin

  • RadiationTBI

    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.

    Also known as: Total body irradiation

  • DrugTacrolimus

    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.

    Also known as: Prograf

  • DrugMMF

    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.

    Also known as: Mycophenolate Mofetil

  • BiologicalPeripheral 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.

  • BiologicalRelated 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.

06

What researchers measure

Primary outcomes

  1. Evaluate rates of acute graft-versus-host disease (GVHD) II-IV

    Percent of subjects with grade II-IV acute GVHD

    Time frame: Day 100 post transplant

Secondary outcomes

  1. Evaluate rates of chronic GVHD

    Percent of subjects with chronic GVHD

    Time frame: 1 year post transplant

  2. Evaluate neutrophil engraftment without ATG (in siblings)

    Percent of subjects with neutrophil engraftment without ATG (in siblings)

    Time frame: Day 42 post transplant

  3. Evaluate neutrophil engraftment with ATG (in unrelated donors)

    Percent of subjects with neutrophil engraftment with ATG (in unrelated donors)

    Time frame: Day 42 post transplant

  4. Evaluate neutrophil engraftment without ATG (in unrelated donors)

    Percent of subjects with neutrophil engraftment without ATG (in unrelated donors)

    Time frame: Day 42 post transplant

  5. Evaluate relapse without ATG (in siblings) - 1 year

    Percent of subjects who relapsed without ATG (in siblings)

    Time frame: 1 year post transplant

  6. Evaluate relapse without ATG (in siblings) - 2 years

    Percent of subjects who relapsed without ATG (in siblings)

    Time frame: 2 years post transplant

  7. Evaluate relapse with ATG (in unrelated donors) - 1 year

    Percent of subjects who relapsed with ATG (in unrelated donors)

    Time frame: 1 year post transplant

  8. Evaluate relapse with ATG (in unrelated donors) - 2 years

    Percent of subjects who relapsed with ATG (in unrelated donors)

    Time frame: 2 years post transplant

  9. Evaluate relapse without ATG (in unrelated donors) - 1 year

    Percent of subjects who relapsed without ATG (in unrelated donors)

    Time frame: 1 year post transplant

  10. Evaluate relapse without ATG (in unrelated donors) - 2 years

    Percent of subjects who relapsed without ATG (in unrelated donors)

    Time frame: 2 years post transplant

  11. Overall survival

    Percent of surviving subjects

    Time frame: Day 100 post transplant

  12. Overall survival

    Percent of surviving subjects

    Time frame: 1 year post transplant

  13. Overall survival

    Percent of surviving subjects

    Time frame: 3 years post transplant

  14. Transplant related mortality (TRM)

    Percent of subjects with TRM

    Time frame: Day 100 post transplant

  15. Transplant related mortality (TRM)

    Percent of subjects with TRM

    Time frame: 1 year post transplant

07

Study locations

1 site
  • Masonic Cancer Center at University of Minnesota
    Minneapolis, Minnesota 55455, United States
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 21, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT02661035
Lead sponsor
Masonic Cancer Center, University of Minnesota
Responsible party
Sponsor
First posted
Jan 21, 2016
Start date
Mar 9, 2017
Primary completion
Apr 17, 2023
Completion
May 29, 2023
Last update
Sep 21, 2023

Study contacts

Erica Warlick, MD
principal investigator · Masonic Cancer Center, University of Minnesota

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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