Allo HSCT Using RIC for Hematological Diseases

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.

An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.

Searching Both is inclusive of interventional and observational studies.

Eligible Ages N/A - 75 Years
Gender All
More Inclusion & Exclusion Criteria

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:

    - 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

Trial Details

Trial ID:

This trial id was obtained from, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.


Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Masonic Cancer Center, University of Minnesota
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Erica Warlick, MD
Principal Investigator Affiliation Masonic Cancer Center, University of Minnesota
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Overall Status Recruiting
Countries United States

The disease, disorder, syndrome, illness, or injury that is being 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
Arms & Interventions


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

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

Drug: - Fludarabine

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

Drug: - Cyclophosphamide

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

Drug: - ATG

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).

Radiation: - TBI

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.

Drug: - Tacrolimus

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.

Drug: - MMF

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.

Biological: - Peripheral 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.

Biological: - Related 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.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Minneapolis, Minnesota




Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, 55455

Site Contact

Tamy Grainger