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)

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02570542

Collaborator

Columbia University (Other), NorthShore University HealthSystem (Other), University of Rochester (Other), Medical College of Wisconsin (Other), University of Nebraska (Other), Sanofi (Industry), University Hospitals Seidman Cancer Center (Other)

Enrollment

Locations

Arms

Anticipated Duration (Months)

4.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B-cell Lymphoma (DLBCL) Relapsed Diffuse Large B-cell Lymphoma (DLBCL) Refractory Diffuse Large B-cell Lymphoma (DLBCL)	Procedure: leukapheresis Drug: Plerixafor Drug: carmustine, etoposide, cytarabine, melphalan Procedure: Autologous Stem Cell Transplantation	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

59 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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)

Actual Study Start Date :

Oct 1, 2015

Anticipated Primary Completion Date :

Oct 1, 2023

Anticipated Study Completion Date :

Oct 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 3-4 x 10^6 CD34+ stem cells/kg 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 Drug: Plerixafor 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. Drug: carmustine, etoposide, cytarabine, melphalan 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. Other Names: BEAM chemotherapy Procedure: Autologous Stem Cell Transplantation
Experimental: 6-8 x10^6 CD34+ stem cells/kg 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 Drug: Plerixafor 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. Drug: carmustine, etoposide, cytarabine, melphalan 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. Other Names: BEAM chemotherapy Procedure: Autologous Stem Cell Transplantation

Arm

Intervention/Treatment

Active Comparator: 3-4 x 10^6 CD34+ stem cells/kg

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

Drug: Plerixafor

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.

Drug: carmustine, etoposide, cytarabine, melphalan

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.

Other Names:

BEAM chemotherapy

Procedure: Autologous Stem Cell Transplantation

Experimental: 6-8 x10^6 CD34+ stem cells/kg

Procedure: leukapheresis

Drug: Plerixafor

Drug: carmustine, etoposide, cytarabine, melphalan

Other Names:

BEAM chemotherapy

Procedure: Autologous Stem Cell Transplantation

Outcome Measures

Primary Outcome Measures

progression-free survival (PFS) [at +/- 2 weeks]
equals date of progression/death - date of Autologous Stem Cell Transplantation

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 Gilbert"s 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-7680
2	Memoral Sloan Kettering Basking Ridge (Consent and Follow-Up Only)	Basking Ridge	New Jersey	United States
3	Memorial Sloan Kettering Monmouth (Consent and Follow up Only)	Middletown	New Jersey	United States	07748
4	Memorial Sloan Kettering Bergen (Consent and Follow Up Only)	Montvale	New Jersey	United States	07645
5	Memorial Sloan Kettering Commack (Consent and Follow-up Only)	Commack	New York	United States	11725
6	Memorial Sloan Kettering Westchester	Harrison	New York	United States	10604
7	Northwell Health	Manhasset	New York	United States	11030
8	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
9	Columbia University	New York	New York	United States
10	University of Rochester Medical Center	Rochester	New York	United States	14642
11	Memorial Sloan Kettering Nassau (Consent and Follow up Only)	Uniondale	New York	United States	11553
12	Tennessee Oncology	Nashville	Tennessee	United States	37203
13	Texas Transplant Institute	San Antonio	Texas	United States	78229
14	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226