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Acute Lymphoblastic LeukemiaPhase 2NCT01119066

HLA-Compatible Related or Unrelated Donors With CD34+ Enriched, T-cell Depleted Peripheral Blood Stem Cells Isolated by the CliniMACS System in the Treatment of Patients With Hematologic Malignancies

A Phase 2 study testing total body irradiation, Thiotepa and Cyclophosphamide in people with Acute Lymphoblastic Leukemia and Acute Myelogenous Leukemia, run by Memorial Sloan Kettering 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 purpose of this study is to find out the effects of using a system called CliniMACS to remove Tcells from blood stem cells. Removing T-cells may help stop a side effect called Graft-Versus-Host Disease (GVHD). Read more about this study

Who is it for?
Ages Up to 69 years
What is being tested?
total body irradiation, Thiotepa and Cyclophosphamide
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
422 participants
Where
1 siteUnited States
Study dates
3 May 2010to 30 Mar 2021
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 69 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Malignant conditions or other life threatening disorders correctable by transplant for which CD34+ selected, T-cell depleted allogeneic hematopoietic stem cell transplantation is indicated such as:
  • AML in 1st remission - for patients whose AML does not have 'good risk' cytogenetic features (i.e. t 8;21, t15;17, inv 16).
  • Secondary AML in 1st remission
  • AML in 1st relapse or > than or = to 2nd remission
  • ALL/CLL in 1st remission clinical or molecular features indicating a high risk for relapse; or ALL/CLL > than or = to 2nd remission
  • CML failing to respond to or not tolerating Imatinib or dasatinib in first chronic phase of disease; CML in accelerated phase second chronic phase or in CR after accelerated phase or blast crisis.
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  • Non-Hodgkins lymphoma with chemoresponsive disease in any of the following categories:
  • intermediate or high grade lymphomas who have failed to achieve a first CR or have relapsed following a 1st remission who are not candidates for autologous transplants.
  • any NHL in remission which is considered not curable with chemotherapy alone and not eligible/appropriate for autologous transplant.
  • Myelodysplastic syndrome (MDS): RA//RARS/RCMD with high risk cytogenetic features or transfusion dependence as well as RAEB-1 and RAEB-2 and Acute myelogenous leukemia (AML) evolved from MDS, who are not eligible for transplantation and/or unable to enroll onto protocol IRB 08-008.
  • Chronic myelomonocytic leukemia: CMML-1 and CMML-2.
  • Multiple Myeloma with disease in the following categories:
  • Patients with relapsed multiple myeloma following autologous stem cell transplantation who have achieved at least partial response following additional chemotherapy.
  • Patients with high risk cytogenetics at diagnosis must have achieved a partial response following autologous stem cell transplantation. Patients must have complex karyotype, del17p, t4;14 and/or t14;16 by FISH and/or del13 by karyotyping.
  • Other rare lethal disorders of Hematopoiesis and Lymphopoiesis for which a T-cell depleted transplant is indicated (e.g. hemophagocytic lymphohistiocytosis; refractory aplastic anemia or congenital cytopenias; non-SCID lethal genetic immunodeficiencies such as Wiskott Aldrich Syndrome, CD40 ligand deficiency, or ALPS, as well as refractory autoimmune cytopenias, PNH, metabolic storage diseases or heavily transfused congenital hemoglobinopathies).
  • Accrual to each treatment arm will include up to 30 standard risk and 30 poor risk patients (60 patients/treatment arm) except for Regimen D, which will include 30 patients/treatment arm, all of which will be poor risk by virtue of risks of relapse and/or transplant related mortality.
  • Standard risk patients will include eligible patients, as defined above, who are receiving transplants as treatment for MDS in RA//RARS/RCMD, AML in 1st or 2nd remission, ALL in 1st CR, NHL in 1st remission, MM in 1st remission, Very Good Partial Response, or 1st Partial Response or CML in the first chronic phase or 1st remission.
  • All other patients, including those with treatment related malignancies and/or those who have AML derived from MDS, will have received extensive prior chemo/radiotherapy and, therefore, will be considered to be at poor risk of conditioning and transplant related morbidities, and potentially transplant related mortality. Patients with life threatening non-malignant genetic and acquired disorders will also, by virtue of their history of, optional transfusions and/or infection be considered poor risk. Stopping rules for non-relapse related mortality in these heavily treated patients are, therefore, slightly less stringent than patients in the poor risk transplant groups. Stopping rules for the principal endpoints of graft failure and GvHD are the same for all groups.
  • The following inclusion criteria are also required:
  • Patient's age includes from birth on to < 70 years old.
  • Patients may be of either gender or any ethnic background.
  • Patients must have a Karnofsky (adult) or Lansky (pediatric) Performance Status > or = to 70%
  • Patients must have adequate organ function measured by:
  • Cardiac: asymptomatic or if symptomatic then LVEF at rest must be > or = to 50% and must improve with exercise.
  • Hepatic: < 3x ULN AST and ≤ to 1.5 total serum bilirubin, unless there is congenital benign hyperbilirubinemia or if the hyperbilirubinemia is directly caused by the disease in which the patient is receiving a transplant (e.g. AML Chloroma obstructing the biliary tree). Patients with higher bilirubin levels due to causes other than active liver disease are also eligible with PI approval e.g. patients with PNH, Gilbert's disease or other hemolytic disorders.
  • Renal: serum creatinine < than or = to 1.2 mg/dl or if serum creatinine is outside the normal range, then CrCl > 40 ml/min (measured or calculated/estimated) Pulmonary: asymptomatic or if symptomatic, DLCO > or = to 50% of predicted (corrected for hemoglobin)
  • Each patient must be willing to participate as a research subject and must sign an informed consent form.

Who cannot join

  • Female patients who are pregnant or breast-feeding
  • Active viral, bacterial or fungal infection
  • Patient seropositive for HIV-I/II; HTLV -I/II
  • Presence of leukemia in the CNS.
  • Donor Inclusion Criteria:
  • Each donor must meet criteria outlined by institutional guidelines
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  • Donor should agree to undergo general anesthesia and bone marrow harvest collection if PBSC yield is inadequate or otherwise not transplantable for whatever reason.
  • Donor Exclusion Criteria
  • If donors do not meet institutional guidelines, exclusion will be considered.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: A Phase II Trial of Transplants From HLA-Compatible Related or Unrelated Donors With CD34+ Enriched, T-cell Depleted Peripheral Blood Stem Cells Isolated by the CliniMACS System in the Treatment of Patients With Hematologic Malignancies and Other Lethal Hematologic Disorders

The purpose of this study is to find out the effects of using a system called CliniMACS to remove Tcells from blood stem cells. Removing T-cells may help stop a side effect called Graft-Versus-Host Disease (GVHD). Some studies have been done with CliniMACS, but the Food and Drug Administration (FDA) has not yet approved it.

Keywords
Leukemia, Multiple Myeloma, radiation, Thiotepa, cyclophosphamide, fludarabine, Clofarabine, CliniMACS device, GCSF, 10-050
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Multiple Myeloma, Leukemia

What participants receive

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

  • total body irradiationRadiation

    dose of 1375-1500 cGy

  • ThiotepaDrug

    5 mg/kg/day x 2 or 10 mg/kg/day x 1

  • CyclophosphamideDrug

    60 mg/ kg/day x 2 (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated).

  • BusulfanDrug

    0.8 mg/kg every 6 hours x 10 or 12 doses (depending on disease) with dose modified according to pharmacokinetics

  • MelphalanDrug

    70mg/m2/day x 2

  • FludarabineDrug

    25mg/m2/ day x 5

  • ClofarabineDrug

    20mg/m2/ day x 5 (or, for children <18 years of age, 30mg/m2/day x 5 if deemed suitable and with PI approval)

  • (CliniMACS) T-cell depleted PBSC TransplantProcedure or surgery

Study groups in NCT01119066
Study groupRoleWhat they receive
Total Body Irradiation, Thiotepa and CyclophosphamideExperimentalHyperfractionated total body irradiation to a dose of 1375-1500 cGy (depending on age, stage of disease and requirement of general anesthesia) with lung shielding) Thiotepa (5 mg/kg/day x 2 or 10 mg/kg/day x 1) Cyclophosphamide (60 mg/kg/day x 2) (or fludarabine 25mg/m2 x 5 if cyclophosphamide is contraindicated)
Receives: Radiation: total body irradiation; Drug: Thiotepa; Drug: Cyclophosphamide; Procedure: (CliniMACS) T-cell depleted PBSC Transplant
Busulfan, Melphalan and FludarabineExperimentalBusulfan (0.8 mg/kg every 6 hours x 10 or 12 doses), (depending on disease) with dose modified according to pharmacokinetics Melphalan (70mg/m2/day x 2 ) Fludarabine (25mg/m2/ day x 5)
Receives: Drug: Busulfan; Drug: Melphalan; Drug: Fludarabine; Procedure: (CliniMACS) T-cell depleted PBSC Transplant
Clofarabine, Melphalan and ThiotepaExperimentalClofarabine (20mg/m2/ day x 5) (or, for children <18 years of age, 30mg/m2/day x 5 if deemed suitable and with PI approval), Melphalan (70 mg/m2/day x 2) Thiotepa (5 mg/kg/day x 2 or 10mg/kg/day x1)
Receives: Drug: Thiotepa; Drug: Melphalan; Drug: Clofarabine; Procedure: (CliniMACS) T-cell depleted PBSC Transplant
Melphalan, Fludarabine and ThiotepaExperimentalMelphalan (70 mg/m2/day x 2) Fludarabine (25mg/m2/ day x 5 ) Thiotepa (5 mg/kg/day x 2 or 10mg/kg/day x1)
Receives: Drug: Thiotepa; Drug: Melphalan; Procedure: (CliniMACS) T-cell depleted PBSC Transplant

What is being measured

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

  1. The Incidence of Durable Hematopoietic Engraftment for T-cell Depleted Transplants Fractionated by the CliniMACS System Administered After Each of the Four Disease Targeted Cytoreduction Regimens.

    Measured: 3 years

  2. Number of Participants With Acute and Chronic GVHD Following T-cell Depleted, CD34+ Progenitor Cell Enriched Transplants Fractionated by the CliniMACS System.

    Standard BMT-CTN and IBMTR systems clinical criteria as defined by Rowlings, et al will be used to establish and grade acute GvHD. Chronic GvHD will be diagnosed and graded according to the criteria of Sullivan (CIBMTR).

    Measured: 3 years

  3. Incidence of Non-relapse Mortality (Transplant-related Mortality) Following Each Cytoreduction Regimen and a Transplant Fractionated by the CliniMACS System.

    Measured: 3 years

  4. Survival and Disease-free Survival (DFS)

    Measured: at 6 months post transplant

  5. Survival and Disease-free Survival (DFS)

    Measured: 1 year post transplant

  6. Survival and Disease-free Survival (DFS)

    Measured: 2 years post transplant

Secondary outcomes (3)
  1. Proportion of Patients Receiving Optimal CD3+ (<1x10^5/kg) Cell Doses the Proportion of Patients Receiving CD3+ T-cell Doses > 1x10^5/kg.

    Measured: Up to 3 years

  2. Proportion of Patients Receiving Optimal CD34+ (> 5x10^6/kg) Cell Doses the Proportion Recurring Suboptimal Doses (< 2x10^6/kg) CD34+ Cells

    Measured: 3 years

  3. Correlation of Doses of CD34+ Progenitors and CD3+ T Cells With Engraftment

    Measured: 3 years

Timeline

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

  1. First posted7 May 2010 (estimated)
  2. Study start3 May 2010
  3. Primary completion30 Mar 2021
  4. Study completion30 Mar 2021

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
Parallel groups
Masking
None (open label)
Enrolment
422 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01119066
Sponsor's protocol ID
10-050
Status last verified
May 2021
First submitted
4 May 2010
Last updated
5 Aug 2022

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing total body irradiation, Thiotepa and Cyclophosphamide in people with Acute Lymphoblastic Leukemia and Acute Myelogenous Leukemia, run by Memorial Sloan Kettering 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 27 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 5 Aug 2022. 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 5 Aug 2022). 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?

The Incidence of Durable Hematopoietic Engraftment for T-cell Depleted Transplants Fractionated by the CliniMACS System Administered After Each of the Four Disease Targeted Cytoreduction Regimens. (time frame: 3 years). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 5 Aug 2022.

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