A Two-Step Approach to Reduced Intensity Bone Marrow Transplant for Patients With Hematological Malignancies

A Two Step Approach to Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Hematologic Malignancies

Sponsors

Lead Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University

Source Thomas Jefferson University
Brief Summary

The purpose of this research study is to compare the survival rates of patients with better risk disease undergoing hematopoietic stem cell transplant (HSCT) to the survival rates reported in the medical literature of similar patients undergoing reduced intensity HSCT from matched related donors.

Detailed Description

PRIMARY OBJECTIVES: I. To compare the overall survival (OS) rate at 2 years post treatment using the Jefferson 2 step reduced intensity conditioning (RIC) approach in patients with haploidentical family donors with hematological malignancies in morphological or radiographic remission or with chemosensitive, indolent diseases to historical OS rates in similar populations after RIC matched donor HSCT as reported in the literature. SECONDARY OBJECTIVES: I. To compare the treatment-related mortality (TRM) rate at 2 years for patients treated on this study to the historical TRM rates of patients undergoing RIC matched-sibling HSCT as reported in the literature. II. To compare the 2 year relapse rates and relapse related mortality of patients with myeloid diseases to that of patients with lymphoid diseases who are treated on this Thomas Jefferson University (TJU) RIC 2 step approach. III. To determine the incidence and severity of graft-versus-host disease (GVHD) in patients undergoing treated on the TJU RIC 2 step approach. IV. To evaluate engraftment rates and lymphoid reconstitution in patients treated on the TJU RIC 2 step approach. V. To evaluate the incidence of TRM at 100 days in patients treated on the TJU RIC 2 step approach. OUTLINE: REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) over 60 minutes on days -11 to -8 and bulsufan IV over 3 hours on days -10 to -9. Patients undergo total body irradiation (TBI) on day -6. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients undergo donor lymphocyte infusion (DLI) on day -6 and cluster of differentiation (CD)-34+ allogeneic peripheral blood stem cell transplantation (PBSCT) on day 0. GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or orally (PO) with taper beginning on day 42. Patients also receive mycophenolate mofetil IV twice daily (BID) on days -1 to 28. After completion of study treatment, patients are followed up periodically for 2 years.

Overall Status Active, not recruiting
Start Date 2011-08-04
Completion Date 2021-07-01
Primary Completion Date 2020-11-13
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Overall Survival (OS) in patients with haploidentical family donors with hematological malignancies in morphological or radiographic remission or with chemosensitive, indolent diseases At 2 years
Secondary Outcome
Measure Time Frame
Treatment Related Mortality (TRM) At 2 years
Incidence and severity of GVHD, graded according to standard criteria Assessed up to 2 years
Relapse Rate At 2 years
Engraftment Rates Assessed up to 2 years
Incidence of Treatment Related Mortality (TRM) At 100 days
Relapse Related Mortality At 2 years
Lymphoid Reconstitution 100 days post-transplant
Enrollment 40
Condition
Intervention

Intervention Type: Drug

Intervention Name: Fludarabine

Description: Given IV

Arm Group Label: Treatment (Allogeneic PBSCT)

Intervention Type: Drug

Intervention Name: Busulfan

Description: Given IV

Arm Group Label: Treatment (Allogeneic PBSCT)

Intervention Type: Radiation

Intervention Name: Total Body Irradiation (TBI)

Description: 2 Gy administered as part of the conditioning regimen

Arm Group Label: Treatment (Allogeneic PBSCT)

Other Name: radiotherapy

Intervention Type: Biological

Intervention Name: Donor Lymphocyte Infusion (DLI)

Description: Undergo DLI

Arm Group Label: Treatment (Allogeneic PBSCT)

Other Name: buffy coat fusion

Intervention Type: Drug

Intervention Name: Cyclophosphamide (CY)

Description: Given IV

Arm Group Label: Treatment (Allogeneic PBSCT)

Intervention Type: Drug

Intervention Name: Tacrolimus

Description: Given IV or PO

Arm Group Label: Treatment (Allogeneic PBSCT)

Intervention Type: Drug

Intervention Name: Mycophenolate mofetil

Description: Given IV

Arm Group Label: Treatment (Allogeneic PBSCT)

Intervention Type: Device

Intervention Name: Allogeneic hematopoietic stem cell transplantation

Description: Undergo CD34+ allogeneic PBSCT

Arm Group Label: Treatment (Allogeneic PBSCT)

Other Name: CliniMACS

Intervention Type: Procedure

Intervention Name: Peripheral blood stem cell transplantation (PBSCT)

Description: Undergo CD34+ allogeneic PBSCT

Arm Group Label: Treatment (Allogeneic PBSCT)

Eligibility

Criteria:

Inclusion Criteria: 1. Any patient with hematologic or oncologic diagnosis in which allogeneic HSCT is thought to be beneficial, and in whom front-line therapy has already been applied. Patients treated on this protocol will be without morphological evidence of disease (complete remission or "CR"), or if the patient has evidence of disease, the patient must have had at least a good partial response (PR) to the most recent therapy and the disease must be chemoresponsive. 2. Patients treated on this study will have: - Acute leukemia in 1st or 2nd CR - MDS (myelodysplastic syndrome), specific subtypes of RA (refractory anemia) or RARS (refractory anemia with ringed sideroblasts) subtypes. - Hodgkin or Indolent Non-Hodgkin's lymphoma with chemosensitive disease - Myeloma without morphological evidence of disease, or a deep PR to the most recent therapy - Myeloproliferative disorders with at least a PR to current therapy - Aplastic Anemia - A hematological or oncological disease (not listed) that meets the criteria reviewed above (in CR or with a good PR). 3. Patients must have a related donor who is HLA mismatched at 2, 3, or 4 antigens at the HLA-A; B; C; DR loci in the GVHD direction. (Patients with related donors who are HLA identical or are a 1-antigen mismatch may be treated on this therapeutic approach, but will have their outcomes will not be part of the statistical aims of the study (see Summary section). 4. Patients must adequate organ function: - LVEF (Left ventricular end diastolic function) of >50% - DLCO (Diffusing Capacity of the Lung for Carbon Monoxide ) ≥50% of predicted corrected for hemoglobin - Adequate liver function as defined by a serum bilirubin <1.8, AST or ALT < 2.5X upper limit of normal - Creatinine Clearance of ≥ 60 mL/min 5. Performance status ≥ 80% (TJU Karnofsky) for patients ≥ 60 years old or ≥70% for patients < 60 years old. 6. HCT-CI Score ≤ 4 points for patients ≥ 60 years old or ≤ 5 points for patients < 60 years old. 7. Patients must be willing to use contraception if they have childbearing potential 8. Able to give informed consent Exclusion Criteria: 1. Performance status < 80% (TJU Karnofsky) for patients ≥ 60 years old or <70% for patients < 60. 2. Hematopoietic Cell Transplant-Comorbidity Index (HCT-CI) Score > 4 points for patients ≥ 60 years old or > 5 points for patients < 60. 3. HIV positive 4. Active involvement of the central nervous system with malignancy 5. Inability to obtain informed consent 6. Pregnancy 7. Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder 8. Patients who have received alemtuzumab within 8 weeks of the transplant admission, or who have recently received horse or rabbit anti-thymocyte globulin and have an anti-thymocyte globulin level of > 2 ugm/ml 9. Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Location
Facility: Thomas Jefferson University
Location Countries

United States

Verification Date

2021-02-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Treatment (Allogeneic PBSCT)

Type: Experimental

Description: REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate IV over 60 minutes on days -11 to -8 and busulfan IV over 3 hours on days -10 to -9. Patients undergo TBI on day -6. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients undergo DLI on day -6 and CD-34+ allogeneic PBSCT on day 0. GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or PO with taper beginning on day 42. Patients also receive mycophenolate mofetil IV BID on days -1 to 28.

Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

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