Umbilical Cord Blood Transplant With Added Sugar and Chemotherapy and Radiation Therapy in Treating Patients With Leukemia or Lymphoma
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| ClinicalTrials.gov Identifier: NCT03096782 |
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Recruitment Status :
Active, not recruiting
First Posted : March 30, 2017
Last Update Posted : May 22, 2019
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive Acute Biphenotypic Leukemia Acute Leukemia Acute Lymphoblastic Leukemia Acute Lymphoblastic Leukemia in Remission Acute Myeloid Leukemia Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome Chemotherapy-Related Leukemia Chronic Lymphocytic Leukemia Chronic Myelogenous Leukemia, BCR-ABL1 Positive Chronic Myelomonocytic Leukemia Hodgkin Lymphoma Langerhans Cell Histiocytosis Minimal Residual Disease Myelodysplastic Syndrome Myelodysplastic Syndrome With Excess Blasts Non-Hodgkin Lymphoma Recurrent Hodgkin Lymphoma Refractory Acute Lymphoblastic Leukemia Refractory Myelodysplastic Syndrome Small Lymphocytic Lymphoma Therapy-Related Myelodysplastic Syndrome | Biological: Anti-Thymocyte Globulin Drug: Busulfan Drug: Clofarabine Drug: Cyclophosphamide Biological: Filgrastim-sndz Drug: Fludarabine Drug: Melphalan Drug: Mycophenolate Mofetil Biological: Rituximab Drug: Tacrolimus Radiation: Total-Body Irradiation Procedure: Umbilical Cord Blood Transplantation | Phase 2 |
PRIMARY OBJECTIVES:
I. To evaluate the safety and feasibility of transplantation of cord blood which is expanded in mesenchymal precursor cell (MPC) co-cultures then fucosylated with fucosyltransferase (FT)-VI and guanosine diphosphate (GDP) fucose prior to infusion in patients with hematologic malignancies following high-dose therapy.
II. To evaluate the time to engraftment using expanded fucosylated cord blood.
SECONDARY OBJECTIVES:
I. To evaluate the rate and severity of graft versus host disease. II. To evaluate the rates of infectious complications. III. To evaluate the rates of disease-free and overall survival.
OUTLINE: Patients are assigned to 1 of 3 groups.
GROUP I: Patients receive rituximab intravenously (IV) on day -11, anti-thymocyte globulin (ATG) IV over 4 hours on days -9 and -8, fludarabine IV over 1 hour, clofarabine IV over 1 hour, busulfan IV over 3 hours on days -7 through -4, and total body irradiation (TBI) on day -3. Patients then receive a cord blood transfusion IV on day 0.
GROUP II: Patients receive ATG IV over 4 hours on days -8 and -7, fludarabine IV over 30 minutes on days -5 to -2, and melphalan IV over 30 minutes on day -2. Patients then receive a cord blood transplant IV on day 0.
GROUP III: Patients receive ATG IV over 4 hours on days -8 and -7, fludarabine IV over 30 minutes on days -6 to -3, cyclophosphamide IV over 1 hour on day -6, and one low-dose treatment of TBI on day -1. Patients then receive a cord blood transplant IV on day 0.
GVHD PROPHYLAXIS: All patients also receive mycofenolate mofetil IV over 2 hours or orally (PO) twice daily (BID) on days -3 with a taper beginning on day 100 in the absence of GVHD, tacrolimus IV or PO starting on day -2 for 6 months in the absence of GVHD, and filgrastim-sndz subcutaneously (SC) once daily (QD) starting on day 0 until white blood count begins to recover.
After completion of study treatment, patients are followed up at months 1, 3, 6, and 12.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 25 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Cord Blood Ex-Vivo MSC Expansion Plus Fucosylation to Enhance Homing and Engraftment |
| Actual Study Start Date : | October 13, 2017 |
| Estimated Primary Completion Date : | October 31, 2020 |
| Estimated Study Completion Date : | October 31, 2020 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Group I (chemotherapy, TBI, cord blood)
Patients receive rituximab IV on day -11, ATG IV over 4 hours on days -9 and -8, fludarabine IV over 1 hour, clofarabine IV over 1 hour, busulfan IV over 3 hours on days -7 through -4, and TBI on day -3. Patients then receive a cord blood transfusion IV on day 0. GVHD PROPHYLAXIS: All patients also receive mycofenolate mofetil IV over 2 hours or PO BID on days -3 with a taper beginning on day 100 in the absence of GVHD, tacrolimus IV or PO starting on day -2 for 6 months in the absence of GVHD, and filgrastim-sndz SC QD starting on day 0 until white blood count begins to recover. |
Biological: Anti-Thymocyte Globulin
Given IV
Other Names:
Drug: Busulfan Given IV
Other Names:
Drug: Clofarabine Given IV
Other Names:
Biological: Filgrastim-sndz Given SC
Other Names:
Drug: Fludarabine Given IV
Other Name: Fluradosa Drug: Mycophenolate Mofetil Given IV or PO
Other Names:
Biological: Rituximab Given IV
Other Names:
Drug: Tacrolimus Given IV
Other Names:
Radiation: Total-Body Irradiation Undergo total body irradiation
Other Names:
Procedure: Umbilical Cord Blood Transplantation Undergo cord blood transplant
Other Names:
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Experimental: Group II (chemotherapy, cord blood)
Patients receive ATG IV over 4 hours on days -8 and -7, fludarabine IV over 30 minutes on days -5 to -2, and melphalan IV over 30 minutes on day -2. Patients then receive a cord blood transplant IV on day 0. GVHD PROPHYLAXIS: All patients also receive mycofenolate mofetil IV over 2 hours or PO BID on days -3 with a taper beginning on day 100 in the absence of GVHD, tacrolimus IV or PO starting on day -2 for 6 months in the absence of GVHD, and filgrastim-sndz SC QD starting on day 0 until white blood count begins to recover. |
Biological: Anti-Thymocyte Globulin
Given IV
Other Names:
Biological: Filgrastim-sndz Given SC
Other Names:
Drug: Fludarabine Given IV
Other Name: Fluradosa Drug: Melphalan Given IV
Other Names:
Drug: Mycophenolate Mofetil Given IV or PO
Other Names:
Drug: Tacrolimus Given IV
Other Names:
Procedure: Umbilical Cord Blood Transplantation Undergo cord blood transplant
Other Names:
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Experimental: Group III (chemotherapy, TBI, cord blood)
Patients receive ATG IV over 4 hours on days -8 and -7, fludarabine IV over 30 minutes on days -6 to -3, cyclophosphamide IV over 1 hour on day -6, and one low-dose treatment of TBI on day -1. Patients then receive a cord blood transplant IV on day 0. GVHD PROPHYLAXIS: All patients also receive mycofenolate mofetil IV over 2 hours or PO BID on days -3 with a taper beginning on day 100 in the absence of GVHD, tacrolimus IV or PO starting on day -2 for 6 months in the absence of GVHD, and filgrastim-sndz SC QD starting on day 0 until white blood count begins to recover. |
Biological: Anti-Thymocyte Globulin
Given IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Biological: Filgrastim-sndz Given SC
Other Names:
Drug: Fludarabine Given IV
Other Name: Fluradosa Drug: Mycophenolate Mofetil Given IV or PO
Other Names:
Drug: Tacrolimus Given IV
Other Names:
Radiation: Total-Body Irradiation Undergo total body irradiation
Other Names:
Procedure: Umbilical Cord Blood Transplantation Undergo cord blood transplant
Other Names:
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- Feasibility of cord blood infusion [ Time Frame: At 12 months after transplant ]Will be defined by sterile expanded mesenchymal stem cell (MSC) product. Feasibility is defined as having a sterile expanded MSC product which was > 50% fucosylated in the majority of the patients enrolled.
- Time to engraftment [ Time Frame: Up to 12 months after transplant ]The distribution of time to engraftment will be estimated using Kaplan-Meier plots and the relationship to covariates evaluated by piecewise exponential Bayesian regression. Time to engraftment will be monitored by the Bayesian statistical method of Thall et al., assuming an accrual rate of 10 patients per year with a maximum sample size of 25 patients. A mean time to engraftment (TTE) of 7 days will be considered desirable and a mean TTE of 21 days will be considered undesirable.
- Disease-free survival [ Time Frame: Up to12 months ]The distribution of disease-free survival time will be estimated using Kaplan-Meier plots and their relationships to covariates evaluated by piecewise exponential Bayesian regression.
- Overall survival [ Time Frame: Up to 12 months after transplant ]The distribution of disease-free survival time will be estimated using Kaplan-Meier plots and their relationships to covariates evaluated by piecewise exponential Bayesian regression.
- Treatment-related mortality (TRM) [ Time Frame: Up to 12 months after transplant ]TRM will be evaluated by tabulation, Kaplan-Meier plots, and piecewise exponential Bayesian regression.
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| Ages Eligible for Study: | 12 Years to 65 Years (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients must have one of the following hematologic malignancies: a. Acute myelogenous leukemia (AML), induction failure, high-risk for relapse first remission (with intermediate-risk or high-risk cytogenetics, flt3 mutation positive and/or evidence of minimal residual disease by flow cytometry), secondary leukemia from prior chemotherapy and/or arising from myelodysplastic syndrome (MDS), Langerhan's cell histiocytosis, any disease beyond first remission. b. Myelodysplastic syndrome (MDS): MDS International Prognostic Scoring System (IPSS) INT-1 will be enrolled only if the subjects have failed previous leukemia treatments and are transfusion-dependent. MDS may be primary or therapy related, including patients that will be considered for transplant. Including the following categories: 1) Revised IPSS intermediate and high risk groups, 2) MDS with transfusion dependency, 3) Failure to respond or progression of disease on hypomethylating agents, 4) Refractory anemia with excess of blasts, 5) Transformation to acute leukemia, 6) Chronic myelomonocytic leukemia, 7) Atypical MDS/myeloproliferative syndromes, 8) Complex karyotype, abn(3g), -5/5g-, -7/7g-, abn(12p), abn(17p). c. Acute lymphoblastic leukemia (ALL) patients with the following will be considered: 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 translocations 9;22 or 4;11, hypodiploidy, complex karyotype, secondary leukemia developing after cytotoxic drug exposure, and/or evidence of minimal residual disease, or acute biphenotypic leukemia which excludes > 7 chromosomal abnormalities, or double hit non-Hodgkin's lymphoma. Non-Hodgkin's lymphoma (NHL) in second or third complete remission or relapse (including relapse post autologous hematopoietic stem cell transplant), or relapsed double hit lymphoma. Small lymphocytic lymphoma (SLL), or chronic lymphocytic leukemia (CLL) with progressive disease with progression after standard of care therapy or have failed/been intolerant to ibrutinib. Chronic myelogenous leukemia (CML) second chronic phase or accelerated phase. Hodgkin's disease (HD): Induction failure after the first complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant), or those with active disease.
- The first 6 patients must be >= 18 and =< 65 years old. The subsequent patients may include pediatric patients >= 12 and =< 65 years old. Eligibility for pediatric patients will be determined in conjunction with an MD Anderson Cancer Center (MDACC) pediatrician.
- Performance score of at least 80% by Karnofsky or performance score (PS) < 3 (Eastern Cooperative Oncology Group [ECOG]) (age >= 12 years)
- Left ventricular ejection fraction of > 40%.
- Pulmonary function test (PFT) demonstrating a diffusion capacity of least 50% predicted.
- Creatinine =< 1.5 mg/dL for patients 12 years old and older and =< 1 for patients younger than 12 years old.
- Serum glutamate pyruvate transaminase (SGPT) =< to 2.0 x normal.
- Bilirubin =< to 2.0 x normal.
- Negative 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 and willing to use an effective contraceptive measure while on study.
- Patients must have two cord blood (CB) units available which are matched with the patient at 4, 5, or 6/6 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).
- Have identified a backup cells source in case of engraftment failure. The source can be autologous, related or unrelated.
- Patient must not have a 10/10 HLA matched family member or unrelated donor.
- Patients will have a back-up graft from any of the following: an available fraction of autologous marrow; or peripheral blood progenitor cells (PBPCs) harvested and cryopreserved; or family member donor; or a third cord blood unit.
- Prior to initiating chemotherapy in this study, twenty-one or more days must have elapsed since the patient's last radiation or chemotherapy administration (Hydrea, Gleevec and other tyrosine kinase inhibitors [TKI] as well as intrathecal therapy are accepted exceptions).
Exclusion Criteria:
- Patients with known history of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS).
- Patients with positive hepatitis serology that is definitive of active disease.
- 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 uncontrolled serious medical condition such as persistent septicemia despite adequate antibiotic therapy, decompensated congestive heart failure despite cardiac medications or pulmonary insufficiency requiring intubation (excluding primary disease for which CB transplantation is proposed), or psychiatric condition that would limit informed consent.
- Positive beta HCG in female of child-bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization or breast-feeding.
- Pediatric patients with acute lymphoblastic leukemia (ALL) that is t (9,22) positive in first remission are not eligible unless there is evidence of minimal residual disease after initial induction and/or consolidation treatment or the pediatric Philadelphia chromosome positive (Ph+) ALL is clinically refractory to available therapies with evidence of persistence in the bone marrow or peripheral blood.
- Patients with options for treatment that are known to be curative are not eligible.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03096782
| United States, Texas | |
| M D Anderson Cancer Center | |
| Houston, Texas, United States, 77030 | |
| Principal Investigator: | Amanda Olson | M.D. Anderson Cancer Center |
Additional Information:
| Responsible Party: | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT03096782 History of Changes |
| Other Study ID Numbers: |
2016-0051 NCI-2018-01236 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 2016-0051 ( Other Identifier: M D Anderson Cancer Center ) P30CA016672 ( U.S. NIH Grant/Contract ) |
| First Posted: | March 30, 2017 Key Record Dates |
| Last Update Posted: | May 22, 2019 |
| Last Verified: | May 2019 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Lymphoma Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Preleukemia Leukemia, Lymphoid Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphocytic, Chronic, B-Cell Hodgkin Disease Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myelomonocytic, Chronic Leukemia, Myelomonocytic, Juvenile Leukemia, Myeloid, Accelerated Phase Neoplasm, Residual Leukemia, Biphenotypic, Acute |
Histiocytosis, Langerhans-Cell Myelodysplastic Syndromes Histiocytosis Anemia, Refractory, with Excess of Blasts Syndrome Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Disease Pathologic Processes Bone Marrow Diseases Hematologic Diseases |