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.
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
- Conditions the study is for
- Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Acute Biphenotypic Leukemia, Acute Lymphoblastic Leukemia in Remission
- What is being tested?
- Allogeneic Hematopoietic Stem Cell Transplantation, Cyclophosphamide and Fludarabine Phosphate
- Type of treatment
- Injection or infusion, Surgery or procedure
- 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
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
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- 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.
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:
- 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:
- 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.
- Conditions
- Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Acute Biphenotypic Leukemia, Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia in Remission, Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, DS Stage II Plasma Cell Myeloma
- Being tested
- Allogeneic Hematopoietic Stem Cell Transplantation, Cyclophosphamide, Fludarabine Phosphate, Laboratory Biomarker Analysis, Lenalidomide
- 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
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
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 group | Role | What they receive |
|---|---|---|
| Treatment Plan 1 (NK cells, umbilical cord blood transplant) | Experimental | Patients 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) | Experimental | Patients 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.
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
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
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)
Proportion of patients with acute graft-versus-host-disease
Measured: Up to 1 year
Proportion of patients with chronic graft-versus-host-disease
Measured: Up to 1 year
Overall survival
The product-limit estimator of Kaplan and Meier will be used with 95% confidence intervals.
Measured: 1 year
Disease-free survival
The product-limit estimator of Kaplan and Meier will be used with 95% confidence intervals.
Measured: 1 year
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
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.
- First posted14 Jun 2012 (estimated)
- Study start3 May 2013
- Primary completionNov 2021 (estimated)
- Study completionNov 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 PositiveStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Chitra Hosing, Principal investigator, M.D. Anderson Cancer Center
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