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Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 PositivePhase 1NCT01619761

NK Cells in Cord Blood Transplantation

A Phase 1 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Cyclophosphamide and Fludarabine Phosphate in people with Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive and Acute Biphenotypic Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This phase I trial studies the side effects and best way to give natural killer cells and donor umbilical cord blood transplant in treating patients with hematological malignancies. Read more about this study

Who is it for?
Ages Up to 75 years
What is being tested?
Allogeneic Hematopoietic Stem Cell Transplantation, Cyclophosphamide and Fludarabine Phosphate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
1 siteUnited States
Study dates
3 May 2013to Nov 2021
Phase
Phase 1
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

  • Patients must have one of the following hematologic malignancies: acute myelogenous leukemia (AML), induction failure, high-risk for relapse first remission (with intermediate-risk or high-risk cytogenetics, fms-related tyrosine kinase 3 [FLT3] mutation positive and/or evidence of minimal residual disease by flow cytometry), secondary leukemia from prior chemotherapy and/or arising from myelodysplastic syndrome, any disease beyond first remission
  • Myelodysplastic syndrome (MDS): primary or therapy related
  • Acute lymphoblastic leukemia (ALL): induction failure, primary refractory to treatment (do not achieve complete remission after first course of therapy) or are beyond first remission including second or greater remission or active disease; patients in first remission are eligible if they are considered high risk, defined as any of the following detected at any time: with t(9;22) or t(4;11), hypodiploidy, complex karyotype, secondary leukemia developing after cytotoxic drug exposure, and/or evidence of minimal residual disease, or acute biphenotypic leukemia, or double hit non-Hodgkin's lymphoma
  • Non-Hodgkin's lymphoma (NHL) in second or third complete remission, refractory NHL, or relapsed NHL (including relapse post autologous hematopoietic stem cell transplant); double hit lymphomas in first remission or more advanced disease
  • Small lymphocytic lymphoma (SLL), or chronic lymphocytic leukemia (CLL) with progressive disease following standard therapy; patients with progressive CLL following standard therapy who meet European Bone Marrow Transplant (EBMT) consensus guidelines of indications for allogeneic stem cell transplantation; this includes patients with (1) lack of response or early relapse within 1 year of receiving a purine analog-containing treatment regimen, (2) disease relapse within 2 years of receiving a purine analog combination therapy or after other therapies such as autologous stem cell transplantation, and (3) CLL associated with tumor protein (p)53 mutations or deletions and/or deletion (del) (17p) requiring therapy; patients must have chemosensitive disease with at least a partial response (PR) or stable disease (SD) with last treatment regimen
  • Chronic myeloid leukemia (CML) second chronic phase or accelerated phase
Show all 22Show fewer
  • Hodgkin's disease (HD): induction failures, second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant)
  • Multiple myeloma: stage II or III, symptomatic, secretory multiple myeloma requiring treatment
  • Performance score of at least 80% by Karnofsky or 0 to 2 Eastern Cooperative Oncology Group (ECOG)
  • Left ventricular ejection fraction greater than 45%
  • Pulmonary function test (PFT) demonstrating a diffusion capacity of least 45% predicted
  • Creatinine < 1.6 mg/dL
  • Serum glutamate pyruvate transaminase (SGPT) =< to 2.0 x normal
  • Bilirubin =< to 2.0 x normal
  • All study participants must be registered into the mandatory Revlimid Risk Evaluation and Mitigation Strategy (REMS) program, and be willing and able to comply with the requirements of the Revlimid REMS program
  • Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS program
  • Negative beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 24 months or no previous surgical sterilization and willing to ongoing pregnancy testing while on treatment with lenalidomide
  • Woman with child bearing potential must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking lenalidomide
  • Men must agree to use a latex condom during sexual contact with females of child bearing potential even if they have had a successful vasectomy
  • Patients must have two CB units available which are matched with the patient at 4, 5, or 6/6 human leukocyte antigen (HLA) class I (serological) and II (molecular) antigens; each cord must contain at least 1.5 x 10^7 total nucleated cells/Kg recipient body weight (pre-thaw); cord blood units will be procured through the National Marrow Donor Program (NMDP)
  • Have identified a backup cells source in case of engraftment failure; the source can be autologous, related or unrelated
  • Patients who have had a prior autologous transplant are eligible

Who cannot join

  • Patients with known history of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS)
  • Active central nervous system (CNS) disease in patient with history of CNS malignancy
  • Patients with chronic active hepatitis or cirrhosis; if positive hepatitis serology, the study chair may deem the patient eligible based on the results of liver biopsy
  • Patients with known hypersensitivity to lenalidomide and/or rituximab
  • Patients who have a matched related donor who is eligible and willing to donate stem cells

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Natural Killer Cells in Allogeneic Cord Blood Transplantation

This phase I trial studies the side effects and best way to give natural killer cells and donor umbilical cord blood transplant in treating patients with hematological malignancies. Giving chemotherapy with or without total body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells and natural killer cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the feasibility and safety of ex-vivo expanded cord blood (CB) natural killer (NK) cells with double CB transplantation in patients with hematological malignancies.

SECONDARY OBJECTIVES:

  1. To monitor engraftment, chimerism, graft versus host disease, and immune reconstitution in patients receiving expanded CB NK cell therapy.

II. To estimate the time to platelet recovery and the time to absolute neutrophil count (ANC) recovery.

III. To estimate overall survival and disease free survival at one year. IV. To study the in-vivo persistence of cord blood NK cells.

OUTLINE:

PREPARATIVE REGIMEN: Patients are assigned to 1 of 2 treatment plans:

TREATMENT PLAN 1: Patients receive high-dose lenalidomide orally (PO) once daily (QD) on days -8 to -2, fludarabine phosphate IV over 1 hour on days -7 to -4, and melphalan IV over 30 minutes on day -4. CD20 positive patients also receive rituximab intravenously (IV) over 6 hours on days -8 to -4.

TREATMENT PLAN 2: Patients receive high-dose lenalidomide PO QD on days -7 to -2, cyclophosphamide IV over 3 hours on day -7, and undergo total body irradiation (TBI) on day -3. Patients also receive rituximab and fludarabine phosphate as in Treatment Plan 1.

NK CELL INFUSION: All patients receive ex-vivo expanded cord blood NK cells IV over 30 minutes on day -2.

TRANSPLANT: All patients undergo allogeneic umbilical cord blood transplant on day 0.

GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: All patients receive tacrolimus IV or PO on days -2 to 180 followed by taper and mycophenolate mofetil IV over 2 hours or PO thrice daily (TID) on days -3 to 100.

After completion of study treatment, patients are followed up at 3, 6, and 12 months.

Medical subject headings
Leukemia, Myeloid, Accelerated Phase, Leukemia, Biphenotypic, Acute, Leukemia, Myeloid, Chronic-Phase, Myelodysplastic Syndromes, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Leukemia, Lymphocytic, Chronic, B-Cell, Hodgkin Disease

What participants receive

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

  • Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT

    Undergo allogeneic umbilical cord blood transplant

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • Fludarabine PhosphateDrug

    Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • LenalidomideDrug

    Also called CC-5013, CC5013, CDC 501, Revlimid

    Given PO

  • MelphalanDrug

    Also called Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard

    Given IV

  • Mycophenolate MofetilDrug

    Also called Cellcept, MMF

    Given IV or PO

  • Natural Killer Cell TherapyBiological

    Given IV

  • RituximabBiological

    Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody

    Given IV

  • TacrolimusDrug

    Also called FK 506, Fujimycin, Hecoria, Prograf

    Given IV or PO

  • Total-Body IrradiationRadiation

    Also called Total Body Irradiation, Whole-Body Irradiation

    Undergo TBI

  • Umbilical Cord Blood TransplantationProcedure or surgery

    Also called Cord Blood Transplantation, UCB transplantation

    Undergo allogeneic umbilical cord blood transplant

Study groups in NCT01619761
Study groupRoleWhat they receive
Treatment Plan 1 (NK cells, umbilical cord blood transplant)ExperimentalPatients receive high-dose lenalidomide PO QD on days -8 to -2, fludarabine phosphate IV over 1 hour on days -7 to -4, and melphalan IV over 30 minutes on day -4. CD20 positive patients also receive rituximab IV over 6 hours on days -8 to -4.
Receives: Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Lenalidomide; Drug: Melphalan; Drug: Mycophenolate Mofetil; Biological: Natural Killer Cell Therapy; Biological: Rituximab; Drug: Tacrolimus; Procedure: Umbilical Cord Blood Transplantation
Treatment Plan 2 (NK cells, umbilical cord blood transplant)ExperimentalPatients receive high-dose lenalidomide PO QD on days -7 to -2, cyclophosphamide IV over 3 hours on day -7, and undergo TBI on day -3. Patients also receive rituximab and fludarabine phosphate as in Treatment Plan 1.
Receives: Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Lenalidomide; Drug: Mycophenolate Mofetil; Biological: Natural Killer Cell Therapy; Biological: Rituximab; Drug: Tacrolimus; Radiation: Total-Body Irradiation; Procedure: Umbilical Cord Blood Transplantation

What is being measured

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

  1. Generation of a minimum of 5 x 10^6 natural killer/kg cells in at least 60% of patients (success rate)

    Will be estimated with 90% credible interval.

    Measured: Up to 1 year

  2. Treatment-related mortality

    The method described by Thall, et al will be used. Will be estimated with 90% credible interval. The product-limit estimator of Kaplan and Meier will be used with 95% confidence intervals.

    Measured: 100 days

  3. Incidence of adverse events graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

    Changes from baseline in vital signs and laboratory values will be summarized. Tabulate adverse events by severity and relationship to therapy.

    Measured: Up to 1 year

Secondary outcomes (6)

  1. Proportion of patients with acute graft-versus-host-disease

    Measured: Up to 1 year

  2. Proportion of patients with chronic graft-versus-host-disease

    Measured: Up to 1 year

  3. Overall survival

    The product-limit estimator of Kaplan and Meier will be used with 95% confidence intervals.

    Measured: 1 year

  4. Disease-free survival

    The product-limit estimator of Kaplan and Meier will be used with 95% confidence intervals.

    Measured: 1 year

  5. Time to initial platelet recovery

    Cumulative incidence of platelet recovery will be estimated with the methods of Gooley, et al.

    Measured: From the infusion of peripheral blood stem cells to the first of 3 consecutive platelet count measurements tested on different days with a count greater than or equal to 20 x 10e9/L, assessed up to 1 year

  6. Time to initial absolute neutrophil count recovery

    Cumulative incidence of platelet recovery will be estimated with the methods of Gooley, et al.

    Measured: From the infusion of peripheral blood stem cells to the first of 3 consecutive days of an absolute neutrophil count greater than or equal to 0.5 x 10e9/L, assessed up to 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 posted14 Jun 2012 (estimated)
  2. Study start3 May 2013
  3. Primary completionNov 2021 (estimated)
  4. Study completionNov 2021 (estimated)

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01619761
Sponsor's protocol ID
2011-0493
Other IDs
NCI-2012-02071, 2011-0493, P30CA016672
Status last verified
Feb 2020
First submitted
12 Jun 2012
Last updated
11 Feb 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Cyclophosphamide and Fludarabine Phosphate in people with Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive and Acute Biphenotypic 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 22 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 11 Feb 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

Results are not available in the source record.

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?

Generation of a minimum of 5 x 10^6 natural killer/kg cells in at least 60% of patients (success rate) (time frame: Up to 1 year). The study lists 3 primary outcomes in all. 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 NCT01619761.

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 11 Feb 2020.

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