Study of the Impact of CD34+ Cell Dose on Absolute Lymphocyte Count Following High-Dose Therapy and Autologous Stem Cell Transplantation for Relapsed and Refractory Diffuse Large B-cell Lymphoma (DLBCL)

Study Overview
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Brief Summary
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The purpose of this study is to study the impact of stem cell dose on outcome after autologous transplant.

Detailed Description
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Following enrollment, patients will be CD34+ stem cell mobilized at the discretion of the treating attending physician with the plerixafor for the achievement of >6 x10^6 CD34+ cells/kg. The patients that fail to mobilize >6 x10^6 CD34+ cells/kg will not be randomized and will subsequently be followed for disease progression and overall survival.. Patients with >6 x10^6 CD34+ cells/kg cryopreserved on study will be admitted to the hospital for planned ASCT. Patients will be randomly infused with either 3-4 x 10^6 CD34+ stem cells/kg or 6-8 x10^6 CD34+ stem cells/kg on d0 per study randomization. The cell dose ranges within the two groups allows variability within aliquots of cells at the time of cryopreservation. Patients will receive standard supportive measures (including: growth factor support post-HDT/ASCT, antimicrobial prophylaxis, red blood cell and platelet transfusion and treatment for neutropenic fever) as per institutional guideline practices.

Official Title
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A Multi-center Randomized Phase II Study of the Impact of CD34+ Cell Dose on Absolute Lymphocyte Count Following High-Dose Therapy and Autologous Stem Cell Transplantation for Relapsed and Refractory Diffuse Large B-cell Lymphoma (DLBCL)

Conditions
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Relapsed Diffuse Large B-cell Lymphoma (DLBCL), Diffuse Large B-cell Lymphoma (DLBCL), Refractory Diffuse Large B-cell Lymphoma (DLBCL)

Intervention / Treatment
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* Procedure: leukapheresis
* Drug: Plerixafor
* Drug: carmustine, etoposide, cytarabine, melphalan
* Procedure: Autologous Stem Cell Transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years old Diagnosed with relapsed or refractory de novo DLBCL or follicular lymphoma transformed to DLBCL to one previous line of anthracycline-containing chemotherapy KPS ≥ 70 Complete or partial response by IWG Working Group or ICML Criteria to maximum of one salvage line of chemotherapy without pre-HDT/ASCT salvage radiotherapy. Eligible for high-dose therapy and autologous stem-cell rescue Serum creatinine ≤ 1.5 mg/dL, or if creatinine >1.5 mg/dL, calculated creatinine clearance of ≥50 mL/min by 24 hour creatinine clearance or CKD-EPI. Last cycle of most recent salvage therapy within 8 weeks of enrollment Total bilirubin < 2.0 mg/dL o If Gilberts disease is suspected and total bilirubin > 2.0 mg/dL, direct bilirubin must be < 2.0 mg/dL Females of childbearing potential and males must agree to use an acceptable form of contraception per institutional practices. Exclusion Criteria: Disease progression by IWG Working Group or ICML Criteria since last therapy Prior autologous or allogeneic stem cell transplantation HIV infection Comorbid condition(s) which, in the opinion of the attending physician and/or MSKCC Principal Investigator, will preclude stem cell mobilization and/or high-dose therapy with autologous stem cell rescue Treatment plan that includes post-transplant maintenance therapy Salvage therapy that includes involved field radiotherapy

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 3-4 x 10^6 CD34+ stem cells/kg<br>Patients will receive standard supportive measures (including: growth factor support post-HDT/ASCT, antimicrobial prophylaxis, red blood cell and platelet transfusion and treatment for neutropenic fever) as per institutional guideline practices. | Procedure: leukapheresis<br> <br> Drug: Plerixafor<br>* Following enrollment, patients will be CD34+ stem cell mobilized at the discretion of the treating attending physician with the plerixafor for a maximum of 4 apheresis days, for the achievement of ≥ 7 x106 CD34+ cells/kg.<br>Drug: carmustine, etoposide, cytarabine, melphalan<br>* Carmustine 300 mg/m2 day -6 Etoposide 100 mg/m2 q12hrs x 8 doses day - 5 thru day -2 Cytarabine 100 mg/m2 q12hrs x 8 doses day - 5 thru day -2 Melphalan 140 mg/m2 day -1 BEAM dosages may be adjusted per institutional dose adjustments based on body weight.<br>* Other names: BEAM chemotherapy;Procedure: Autologous Stem Cell Transplantation<br> <br> |
| Experimental: 6-8 x10^6 CD34+ stem cells/kg<br>Patients will receive standard supportive measures (including: growth factor support post-HDT/ASCT, antimicrobial prophylaxis, red blood cell and platelet transfusion and treatment for neutropenic fever) as per institutional guideline practices. | Procedure: leukapheresis<br> <br> Drug: Plerixafor<br>* Following enrollment, patients will be CD34+ stem cell mobilized at the discretion of the treating attending physician with the plerixafor for a maximum of 4 apheresis days, for the achievement of ≥ 7 x106 CD34+ cells/kg.<br>Drug: carmustine, etoposide, cytarabine, melphalan<br>* Carmustine 300 mg/m2 day -6 Etoposide 100 mg/m2 q12hrs x 8 doses day - 5 thru day -2 Cytarabine 100 mg/m2 q12hrs x 8 doses day - 5 thru day -2 Melphalan 140 mg/m2 day -1 BEAM dosages may be adjusted per institutional dose adjustments based on body weight.<br>* Other names: BEAM chemotherapy;Procedure: Autologous Stem Cell Transplantation<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival (PFS) | equals date of progression/death - date of Autologous Stem Cell Transplantation | at +/- 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the impact of CD34+ cell dose on lymphocyte subset recovery | (ALC15) post HDT-ASCT Accordingly, each subject will be classified as a responder (i.e., recovery) or non-responder. | day 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD34+ Cell Dose, Autologous Stem Cell Transplantation, 15-193