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Acute Myelogenous LeukemiaPhase 2NCT02661035

Allo HSCT Using RIC for Hematological Diseases

A Phase 2 study testing Allopurinol, Fludarabine and Cyclophosphamide in people with Acute Myelogenous Leukemia and Acute Lymphocytic Leukemia, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages Up to 75 years
What is being tested?
Allopurinol, Fludarabine and Cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
156 participants
Where
1 siteUnited States
Study dates
9 Mar 2017to 29 May 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 75 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
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  • 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)

Who cannot join

  • 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
Show all 9Show fewer
  • 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 locations and contacts

1 site in 1 country.

United States1 site

  • Masonic Cancer Center at University of Minnesota

    Minneapolis, Minnesota, 55455

Other trials in United States

About this study

Official title: Allogeneic Hematopoietic Stem Cell Transplantation Using Reduced Intensity Conditioning (RIC) for the Treatment of Hematological Diseases [MT2015-32]

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.

Being tested
Allopurinol, Fludarabine, Cyclophosphamide, ATG, TBI
Keywords
AML, ALL, CML, MDS, CLL, SLL, NHL
Medical subject headings
Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Plasma Cell, Myelodysplastic Syndromes, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, B-Cell, Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AllopurinolDrug

    Also called Zyloprim

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

  • FludarabineDrug

    Also called Fludara

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

  • CyclophosphamideDrug

    Also called Cytoxan

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

  • ATGDrug

    Also called Anti-thymocyte globulin

    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).

  • TBIRadiation

    Also called Total body irradiation

    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.

  • TacrolimusDrug

    Also called Prograf

    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.

  • MMFDrug

    Also called Mycophenolate Mofetil

    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.

  • Peripheral Blood Stem CellsBiological

    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.

  • Related or Unrelated Bone Marrow CellsBiological

    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.

Study groups in NCT02661035
Study groupRoleWhat they receive
Reduced Intensity ConditioningExperimentalNon-myeloablative cyclophosphamide/ fludarabine/total body irradiation (TBI) preparative regimen followed by a related or unrelated donor stem cell infusion
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Percent of subjects with grade II-IV acute GVHD

    Measured: Day 100 post transplant

Secondary outcomes (15)

  1. Evaluate rates of chronic GVHD

    Percent of subjects with chronic GVHD

    Measured: 1 year post transplant

  2. Evaluate neutrophil engraftment without ATG (in siblings)

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

    Measured: Day 42 post transplant

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

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

    Measured: Day 42 post transplant

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

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

    Measured: Day 42 post transplant

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

    Percent of subjects who relapsed without ATG (in siblings)

    Measured: 1 year post transplant

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

    Percent of subjects who relapsed without ATG (in siblings)

    Measured: 2 years post transplant

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

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

    Measured: 1 year post transplant

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

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

    Measured: 2 years post transplant

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

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

    Measured: 1 year post transplant

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

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

    Measured: 2 years post transplant

  11. Overall survival

    Percent of surviving subjects

    Measured: Day 100 post transplant

  12. Overall survival

    Percent of surviving subjects

    Measured: 1 year post transplant

  13. Overall survival

    Percent of surviving subjects

    Measured: 3 years post transplant

  14. Transplant related mortality (TRM)

    Percent of subjects with TRM

    Measured: Day 100 post transplant

  15. Transplant related mortality (TRM)

    Percent of subjects with TRM

    Measured: 1 year post transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jan 2016 (estimated)
  2. Study start9 Mar 2017
  3. Primary completion17 Apr 2023
  4. Study completion29 May 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
156 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02661035
Sponsor's protocol ID
2015LS152
Status last verified
Sep 2023
First submitted
19 Jan 2016
Last updated
21 Sep 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Allopurinol, Fludarabine and Cyclophosphamide in people with Acute Myelogenous Leukemia and Acute Lymphocytic Leukemia, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Evaluate rates of acute graft-versus-host disease (GVHD) II-IV (time frame: Day 100 post transplant). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02661035.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2023.

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