Donor Umbilical Cord Blood Transplant By Injection Into the Bone Marrow in Treating Patients With Hematologic Cancer

Study Overview
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Brief Summary
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Rationale: Giving chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from the donor's umbilical cord blood are injected into the patient's bone marrow they may help make stem cells, red blood cells, white blood cells, and platelets. Purpose: This phase I/II trial is studying the side effects of donor umbilical cord blood transplant when given directly into the bone marrow and to see how well it works in treating patients with hematologic cancer.

Detailed Description
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Objectives: Primary Determine the safety, in terms of infusional toxicity, of myeloablative unrelated donor double-unit umbilical cord blood (UCB) transplantation via intra-bone marrow injection (IBMI) in patients with advanced or high-risk hematologic malignancy. Determine whether treatment with this regimen improves the time to neutrophil engraftment (compared to historical controls) in these patients. Secondary Determine the incidence of sustained donor engraftment in patients treated with this regimen. Determine the relative contribution of each UCB unit to initial and sustained donor engraftment in these patients. Determine the incidence of grade II-IV and grade III-IV acute graft-vs-host disease (GVHD) and chronic GVHD in patients treated with this regimen. Determine the incidence of day 100 and 180 transplant-related mortality in patients treated with this regimen. Determine the probability of survival at 100 days and 1 year post-transplantation in these patients. Outline: This is a nonrandomized study. Patients receive a myeloablative conditioning regimen. Patients also receive immunosuppression, growth factor, and supportive care as in protocol MT2005-10 (NCT00309842). Patients receive 2 units of donor umbilical cord blood (UCB) by intra-bone marrow injection (IBMI) over 10 minutes each on day 0. If the IBMI procedure is not possible, then the UCB units are given intravenously (IV.) After completion of study therapy, patients are followed periodically for 5 years. Projected Accrual: A total of 36 patients will be accrued for this study.

Official Title
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A Phase I/II Study of Double Unit Umbilical Cord Blood (UCB) Transplantation Utilizing Graft Administration Via Intra-Bone Marrow Injection (Companion Protocol to MT2000-25)

Conditions
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Myeloproliferative Disorders, Leukemia, Lymphoma, Myelodysplastic Syndromes

Intervention / Treatment
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* Procedure: umbilical cord blood transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute myeloid leukemia (AML): high risk CR1 Acute lymphocytic leukemia (ALL): high risk CR1 [t(9;22), t (1:19), t(4;11) or other MLL rearrangements] or > 1 cycle to obtain CR; CR2+. All patients must be in CR as defined by hematological recovery, AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%. Chronic myelogenous leukemia (CML) excluding refractory blast crisis. To be eligible in first chronic phase (CP1) patient must have failed or be intolerant to imatinib mesylate. Myelodysplasia (MDS) IPSS Int-2 or High risk (i.e. RAEB, RAEBt) or refractory anemia with severe pancytopenia or high risk cytogenetics. Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma or follicular lymphoma that have progressed after at least two prior therapies. Patients with bulky disease (nodal mass greater than 5 cm). Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are eligible after initial therapy in CR1+ or PR1+. Large cell NHL > CR2/> PR2. Patients in CR2/PR2 with initial short remission (<6 months) are eligible. Lymphoblastic lymphoma. Multiple myeloma beyond PR2. Karnofsky performance status (PS) 90-100% (adults) Lansky PS 50-100% (children) Acceptable organ function Exclusion Criteria: Active infection at time of transplantation History of HIV infection Pregnant or breast feeding. Chemotherapy refractory large cell and high grade NHL (ie progressive disease after > 2 salvage regimens) Extensive prior therapy including > 12 months alkylator therapy or > 6 months alkylator therapy with extensive radiation. Diffuse myelofibrosis of BM (bone marrow) (any severity) regardless of primary diagnosis (focal fibrosis acceptable provided it involves < 20% of BM volume). History of pelvic irradiation.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transplant Patients<br>Patients receiving umbilical cord blood transplantation. | Procedure: umbilical cord blood transplantation<br>* The graft will be given by slow injection into each posterior iliac crest.<br>* Other names: UCBT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Number of Days to Neutrophil Engraftment | Number of days to neutrophil recovery observed in recipients of two umbilical cord blood units (UCB)administered i.v. Neutrophil recovery is defined as first of 3 consecutive days with ANC (absolute neutrophil count) greater than or equal to 500/ul. | Daily through Day 60 post transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Achieving Neutrophil Recovery | Number of patients with sustained neutrophil recovery with chimerism (evidence of engraftment of both cord blood transplants) at 6 months. | 6 months | 
| Number of Patients With Evidence of Engraftment. | Number of patients who received both cord blood units and achieved sustained donor engraftment | 1 year | 
| Number of Patients With Acute Graft-versus-host Disease (GVHD) | Number of patients who exhibited grade II-IV acute GVHD at 100 days post umbilical cord blood transplant. | 100 days post transplant | 
| Number of Patients With Transplant-related Mortality (TRM) | Number of patients who were deceased at days 100 and 180 from any cause other than relapse. | Day 100 and Day 180 | 
| Number of Patients Surviving at Day 100 and 1 Year. | Overall survival of patients-Number of patients who were alive at Day 100 and 1 year post transplant. | Day 100 and 1 year | 
| Number of Patients With Grade III-IV Acute Graft-versus-host Disease (GVHD) | Number of umbilical cord blood transplant patients developing severe GVHD at 100 days post transplant. | 100 days post transplant | 
| Number of Patients With Chronic Graft-versus-host Disease (GVHD). | Number of umbilical cord blood transplant patients with limited and extensive chronic GVHD. | 1 year post transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mantle cell lymphoma, adult acute myeloid leukemia in remission, adult acute myeloid leukemia, childhood acute myeloid leukemia in remission, secondary acute myeloid leukemia, accelerated phase chronic myelogenous leukemia, childhood chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, refractory anemia with excess blasts, de novo myelodysplastic syndromes, myelodysplastic syndromes, adult diffuse large cell lymphoma, adult diffuse mixed cell lymphoma, adult diffuse small cleaved cell lymphoma, adult lymphoblastic lymphoma, grade 3 follicular lymphoma, childhood large cell lymphoma, childhood lymphoblastic lymphoma, adult acute lymphoblastic leukemia, acute lymphoblastic leukemia, refractory anemia, refractory cytopenia, childhood acute myeloid leukemia, adult immunoblastic large cell lymphoma, blastic phase chronic myelogenous leukemia, chronic eosinophilic leukemia, chronic neutrophilic leukemia, childhood small noncleaved cell lymphoma, childhood myelodysplastic syndromes