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Blood Stem Cell Transplant FailurePhase 2NCT01010217

Mismatched Transplantation Using High-dose Post-transplant Cyclophosphamide

A Phase 2 study testing Cyclophosphamide, Fludarabine and Melphalan in people with Blood Stem Cell Transplant Failure and Leukemia, run by M.D. Anderson Cancer Center 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

The goal of this clinical research study is to learn about the safety of giving a stem cell transplant from a tissue-mismatched donor, followed by cyclophosphamide, to patients with certain types of blood disorders or blood cancers. Melphalan, thiotepa, and fludarabine will also be given before the transplant. Read more about this study

Who is it for?
Ages Up to 75 years
What is being tested?
Cyclophosphamide, Fludarabine and Melphalan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
176 participants
Where
1 siteUnited States
Study dates
5 Nov 2009to 5 Oct 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Patients < 55 years (Myeloablative regimen #1) or > 55 and </= 75 years or significant comorbidities (Reduced intensity regimen #2) old lacking a matched related volunteer donor identified in time for transplant for which a related haploidentical donor (</= 7/8 allele match at the A, B, C, DR loci), a 7/8 allele matched related or unrelated donor is identified, or a matched unrelated donor (MUD). The patients must be diagnosed with a high-risk disease defined as following:
  • Acute lymphocytic leukemia (ALL) in CR1 with high-risk features including adverse cytogenetics such as t(9;22), t(1;19), t(4;11), or MLL gene rearrangements; ALL in second or greater remission or ALL with relapsed disease, peripheral blood blasts < 1000/microliter, ALL patients must show response to most recent received chemotherapy;
  • Acute myeloid leukemia (AML) in CR1 with intermediate-risk disease or high-risk features defined as: Greater than 1 cycle of induction therapy required to achieve remission; Preceding myelodysplastic syndrome (MDS) or myeloproliferative disease; Presence of FLT3 mutations or internal tandem duplications; FAB M6 or M7 classification; Adverse cytogenetics, -5, del 5q, -7, del7q, abnormalities involving 3q, 9q, 11q, 20q, 21q, 17, +8 [> 3 abnormalities], peripheral blood blasts <1000/microliter, AML patients must show response to most recent received chemotherapy;
  • AML in second or greater remission, primary induction failure and patients with relapsed disease, peripheral blood blasts <1000/microliter; patients > 55 years and </= 75 years need to be in morphologic remission at transplant (< 5% blasts).
  • Myelodysplastic syndrome (MDS) with International Prognostic Scoring System (IPSS) intermediate-2 or higher; or therapy-related MDS
  • Aplastic anemia with Absolute neutrophil count (ANC)<1000 and transfusion dependent after they failed immunosuppression therapy
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  • Chronic myeloid leukemia (CML) >/=1st chronic phase, after failed >/=2 lines of tyrosine kinase inhibitors; in accelerated or blast phase with > 30% bone marrow blasts;
  • Prior allogeneic stem cell transplant more than 6 months from the first transplant, in remission.
  • Chemotherapy-sensitive relapsed lymphoma (Complete or partial response), Hodgkin's or non-Hodgkin's lymphoma, no evidence of "bulky" disease (> 10 cm in diameter);
  • Patients with chemo-sensitive CLL with persistent or recurrent disease after fludarabine-based regimens, no evidence of "bulky" disease (> 10 cm in diameter)
  • Patients with poor prognosis multiple myeloma by cytogenetics (del13, del 17p, t(1;14) or t(14;16) or hypodiploidy, with advanced disease (stage>/=2) and /or relapsed after autologous stem cell transplant.
  • Patients with myelofibrosis (Lille >0, transfusion dependency, progression to blast phase; however, in remission from AML) or chronic myelomonocytic leukemia (CMML). These patients will be treated with the reduced-intensity conditioning regimen #2 and will be subject to the same stopping rule as the group >/= 55 years or with comorbidities.
  • Zubrod performance status 0-1 or Lansky PS greater or equal to 70%.
  • Patients above >/=65 years old should have an age-adjusted co-morbidity index of </= 3.
  • Available donor able to undergo a bone marrow harvest. For matched unrelated donor transplants only: Peripheral blood stem cells may be collected if donor is unavailable for bone marrow harvest or if adequate bone marrow cannot be collected.
  • Bilirubin </= 1.5 mg/dl (unless Gilbert's syndrome), ALT or AST </= 200 IU/ml.
  • Serum creatinine clearance >/=50 ml/min (calculated with Cockcroft-Gault formula); Creatinine for children </=1.5 mg/dl or </=2 times upper limit of normal for age (whichever is less);
  • Diffusing capacity for carbon monoxide (DLCO) >/= 45% predicted corrected for hemoglobin. For pediatric patients, if unable to perform pulmonary function, >/= 92% oxygen saturation with pulse oximetry.
  • Left ventricular ejection fraction (LVEF) >/= 40%.
  • Patient or patient's legal representative, parent(s) or guardian should provide written informed consent. Assent of a minor if participant's age is at least seven and less than eighteen years.

Who cannot join

  • HIV positive; active hepatitis B or C
  • Patients with active infections. The PI is the final arbiter of the eligibility.
  • Liver cirrhosis with greater than grade 1 stage 1 inflammation/fibrosis
  • Uncontrolled central nervous system (CNS) involvement by tumor cells
  • Patients with AML must have less than 30% bone marrow blasts and no peripheral blood blasts.
  • History of another primary malignancy that has not been in remission for at least 3 years. (The following are exempt from the 3-year limit: non-invasive nonmelanoma skin cancer, fully excised melanoma in situ [Stage 0], curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on PAP smear.)
  • Positive Beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization.
  • Inability to comply with medical therapy or follow-up.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Three-arm Clinical Trial for Patients With Hematologic Malignancies and Mismatched Donors - Haploidentical, 1 Antigen Mismatch Related or Unrelated, and Matched Unrelated Donor (MUD)- Using a T-cell Replete Allograft and High-dose Post-transplant Cyclophosphamide

The goal of this clinical research study is to learn about the safety of giving a stem cell transplant from a tissue-mismatched donor, followed by cyclophosphamide, to patients with certain types of blood disorders or blood cancers. Melphalan, thiotepa, and fludarabine will also be given before the transplant.

Researchers will study the health status of these patients at 3 months after the transplant.

Read the detailed description

The Study Treatment:

Cyclophosphamide is designed to interfere with the multiplication of cancer cells, which may slow or stop their growth and spread throughout the body. This may cause the cancer cells to die.

In this study, researchers want to learn if cyclophosphamide can help to prevent graft-versus-host disease (GVHD -- when transplanted immune tissue, such as white blood cells, attacks the tissues of the recipient's body).

Melphalan, thiotepa, and fludarabine are commonly used in combination with a stem cell transplant.

Study Treatment Administration:

If you are found to be eligible to take part in this study, you will receive chemotherapy for 6 days:

  • You will receive melphalan by vein over 30 minutes on Day -8 (8 days before the transplant).
  • You will receive thiotepa by vein over 4 hours on Day -7.
  • You will receive fludarabine by vein over 1 hour on Days -6, -5, -4, and -3.

If thiotepa is not available, you will receive melphalan by vein over 30 minutes on Day -6 and fludarabine by vein over 1 hour on Days -5, -4, -3, and -2. You will receive total body irradiation (TBI) on Day -1.

On Day 0, you will receive the donor's stem cells by vein. This may last anywhere from 15 minutes to several hours.

On Days 3 and 4, you will receive cyclophosphamide by vein over 3 hours. You will also receive mesna by vein over 30 minutes every 4 hours for a total of 10 mesna doses on Days 3 and 4. Mesna is given to lower the risk of side effects to the bladder.

Starting on Day 5, you will receive tacrolimus and mycophenolate mofetil (MMF) to help lower the risk of GVHD. Tacrolimus will be given by vein as a continuous infusion for about 2 weeks. After the 2 weeks of taking tacrolimus by vein, you will take tacrolimus by mouth as a pill for at least 3 months. MMF will be given by mouth, 3 times a day, usually until Day 35.

Starting on Day 7, you will receive filgrastim (G-CSF) once a day as an injection under the skin, until your blood cell counts reach a high enough level.

Depending on the type of disease that you have, your doctor may decide to give you rituximab by vein over several hours on Days -13, -6, 1, and 8. Rituximab is given to help the body get rid of abnormal white blood cells.

Length of Study Participation:

You will be in the hospital for about 4 weeks after the transplant. You will be taken off study if the disease gets worse. The study drugs will be stopped if intolerable side effects occur.

Follow-Up Visits:

You will be asked to stay close enough to Houston to be able to come back for any visits for at least 100 days after the transplant.

At 1, 3, 6, and 12 months after the transplant, the following tests and procedures will be performed:

  • You will have a physical exam.
  • Blood (about 4 tablespoons) will be drawn for routine tests.
  • You will have a bone marrow biopsy/aspirate to check the status of the disease. If you have lymphoma or aplastic anemia, you may have a bone marrow biopsy/aspirate at 3, 6, and 12 months, if your doctor thinks it is needed.
  • Blood (about 4 tablespoons) will be drawn to measure tumor cells and to predict graft failure and/or relapse.
  • You may have urine collected and/or scans performed such as x-rays, CT scans, and/or a positron emission tomography (PET) scan. These scans and urine tests would only be done if the study doctor thinks they are needed to check the status of the disease.
  • Blood (about 4 tablespoons) will be drawn to check your immune system.

If you have AML, at 2 months after the transplant, blood (about 4 tablespoons) will be drawn to check your immune system.

If you have MM, you will have a bone survey once a year.

If the study doctor thinks it is needed based on side effects you may be having, additional follow-up tests will be performed.

You may be contacted by phone 1-2 times a year to ask about the status of the disease. These calls will take about 10 minutes to complete.

This is an investigational study. All of the drugs used in this study are commercially available and FDA approved. However, it is investigational to give high-dose cyclophosphamide for preventing GVHD that may occur after a stem cell transplant from a tissue-mismatched donor.

Up to 337 patients will take part in this study. All will be enrolled at MD Anderson.

Keywords
Hematologic Neoplasms, Blood Disorders, Blood Cancer, Transplantation, Blood And Marrow, Acute myelogenous leukemia, Myelodysplastic syndrome, Acute lymphocytic leukemia, Aplastic anemia, Chronic myelogenous leukemia, Chronic lymphocytic leukemia, Myeloproliferative disease, Hodgkin's disease, Non-Hodgkin's lymphoma, Multiple myeloma, Cyclophosphamide, Fludarabine, Melphalan, Mesna, Rituximab, Tacrolimus
Medical subject headings
Leukemia, Hematologic Neoplasms, Hematologic Diseases, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Anemia, Aplastic, Leukemia, Myelogenous, Chronic, BCR-ABL Positive

What participants receive

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

  • CyclophosphamideDrug

    Also called Cytoxan, Neosar

    50 mg/kg/day intravenous (IV) over 3 hours on Days 3 and 4.

  • FludarabineDrug

    Also called Fludara, Fludarabine Phosphate

    40 mg/m^2 IV over 1 hour on Days -6, -5, -4, and -3.

  • MelphalanDrug

    Also called Alkeran

    140 mg/m^2 IV (or 100 mg/m^2 with reduced intensity Regimen 2) over 30 minutes on Day -8.

  • MesnaDrug

    Also called Mesnex

    10 mg/kg IV every 4 hours for a total of 10 doses starting just prior to first dose of Cyclophosphamide on Days 3 and 4.

  • RituximabDrug

    Also called Rituxan

    CD20+ lymphoid malignancies: 375 mg/m2 on Day -13 followed by 1000 mg/m2 on Day -6, +1, and +8.

  • Stem Cell TransplantationProcedure or surgery

    Also called SCT, Blood Marrow Transplantation, Allogeneic stem cell transplantation, ASCT

    Infusion of donor's stem cells by vein on Day 0, may last anywhere from 15 minutes to several hours.

  • ThiotepaDrug

    5 mg/kg Regimen 1 (or 5 mg/kg with reduced intensity Regimen 2) IV over 4 hours on Day -7.

  • TacrolimusDrug

    Also called Prograf

    0.015 mg/kg by vein or orally daily starting on Day +5 for 3 months

  • Mycofenolate mofetilDrug

    Also called MMF, CellCept

    15 mg/kg/dose orally three times a day starting on Day +5 to Day +100 or otherwise indicated

  • G-CSFDrug

    Also called Filgrastim, Neupogen

    5 mcg/kg/day subcutaneously starting Day 7 once a day daily until neutrophil recovery > 1000/mcl.

Study groups in NCT01010217
Study groupRoleWhat they receive
Haploidentical relatedExperimentalArm 1 - Stem Cell Transplantation (SCT), Melphalan 140 mg/m^2 , Thiotepa 5 mg/kg, Fludarabine 40 mg/m^2 + high-dose post-transplant cyclophosphamide 50 mg/kg/day
Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Melphalan; Drug: Mesna; Drug: Rituximab; Procedure: Stem Cell Transplantation; Drug: Thiotepa; Drug: Tacrolimus; Drug: Mycofenolate mofetil; Drug: G-CSF
1 Antigen Mismatch Related or UnrelatedExperimentalArm 2 - SCT, Melphalan, Thiotepa, Fludarabine + high-dose post-transplant cyclophosphamide.
Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Melphalan; Drug: Mesna; Drug: Rituximab; Procedure: Stem Cell Transplantation; Drug: Thiotepa; Drug: Tacrolimus; Drug: Mycofenolate mofetil; Drug: G-CSF
Matched Unrelated Donor (MUD)ExperimentalArm 3 - SCT, Melphalan, Thiotepa, Fludarabine + high-dose post-transplant cyclophosphamide
Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Melphalan; Drug: Mesna; Drug: Tacrolimus; Drug: Mycofenolate mofetil; Drug: G-CSF

What is being measured

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

  1. Number of Participants With Non-relapse Mortality (NRM)

    Non-relapse mortality (NRM) is defined as death from any cause other than relapse disease. Bayesian monitoring scheme described in Thall, Simon, and Estey (1996) employed to perform interim monitoring of the data during the course of the trial separately within each group.

    Measured: At 100 days

Secondary outcomes (5)

  1. Number of Participants With Non Related Mortality (NRM)

    Non-relapse mortality (NRM) is defined as death from any cause other than relapse disease.

    Measured: six months

  2. Engraftments

    Measured: Day 28

  3. Grade III-IV aGVHD

    Acute Graft vs host disease

    Measured: 100 days

  4. cGVHD

    Chronic graft vs host disease

    Measured: 1 year

  5. Disease Free Survival

    Participants who have survived without their original disease.

    Measured: 1 year

Timeline

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

  1. First posted9 Nov 2009 (estimated)
  2. Study start5 Nov 2009
  3. Primary completion5 Oct 2017
  4. Study completion5 Oct 2017

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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
176 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01010217
Sponsor's protocol ID
2009-0266
Other IDs
NCI-2011-03144
Status last verified
Mar 2020
First submitted
6 Nov 2009
Last updated
25 Mar 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cyclophosphamide, Fludarabine and Melphalan in people with Blood Stem Cell Transplant Failure and Leukemia, run by M.D. Anderson Cancer Center 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 20 inclusion and 8 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 25 Mar 2020. 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?

Yes. Results are posted in the registry (first posted 7 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With Non-relapse Mortality (NRM) (time frame: At 100 days). 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 NCT01010217.

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 25 Mar 2020.

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