Reduced-Intensity Conditioning Before Donor Stem Cell Transplant in Treating Patients With High-Risk Hematologic Malignancies

A Two Step Approach to Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation for High Risk Hematologic Malignancies

Sponsors

Lead Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University

Source Thomas Jefferson University
Brief Summary

This clinical trial studies reduced-intensity conditioning before donor stem cell transplant in treating patients with high-risk hematologic malignancies. Giving low-doses of chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect.

Detailed Description

PRIMARY OBJECTIVE: 1. To compare the rate of disease-free survival (DFS) at 1 year post hematopoietic stem cell transplant (HSCT) in patients undergoing HSCT treated on this successor Thomas Jefferson University (TJU) 2 Step reduced intensity conditioning (RIC) haploidentical regimen and compare it with that of the initial 2 Step RIC regimen. SECONDARY OBJECTIVES: 1. To assess the 100 day regimen-related mortality (RRM) in patients undergoing HSCT on this treatment protocol. 2. To determine the incidence and severity of graft-versus-host disease (GVHD) in patients undergoing treatment on this regimen. 3. To evaluate engraftment rates and lymphoid reconstitution in patients treated on this trial. 4. To assess overall survival at 1 and 3 years past HSCT in patients treated on this trial. OUTLINE: REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) over 60 minutes on days -15 to -12, thiotepa IV over 2 hours on days -15 to -13, donor lymphocyte infusion (DLI) on day -6, and cyclophosphamide IV over 2 hours on days -3 and -2. Patients also undergo total-body irradiation (TBI) on day -10. TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant (PBSCT) on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV on days -1 to 42 followed by taper and mycophenolate mofetil IV twice daily (BID) on days -1 to 28. After completion of study treatment, patients are followed up periodically.

Overall Status Recruiting
Start Date 2012-12-24
Completion Date 2022-09-01
Primary Completion Date 2022-07-01
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Disease-free survival (DFS) 1 year
Secondary Outcome
Measure Time Frame
Overall survival 1 year and 3 years
Incidence of Regimen Related Toxicity Up to 1 year
Immune reconstitution Up to 1 year
Incidence and degree of GVHD Up to 1 year
Engraftment rates Up to 1 year
Enrollment 72
Condition
Intervention

Intervention Type: Drug

Intervention Name: Fludarabine phosphate

Description: Given IV

Arm Group Label: Treatment (RIC and stem cell transplant)

Intervention Type: Drug

Intervention Name: Thiotepa

Description: Given IV

Arm Group Label: Treatment (RIC and stem cell transplant)

Intervention Type: Radiation

Intervention Name: Total body irradiation

Description: Undergo TBI

Arm Group Label: Treatment (RIC and stem cell transplant)

Other Name: TBI

Intervention Type: Biological

Intervention Name: Therapeutic allogeneic lymphocytes

Description: Undergo donor lymphocyte infusion

Arm Group Label: Treatment (RIC and stem cell transplant)

Intervention Type: Drug

Intervention Name: Cyclophosphamide

Description: Given IV

Arm Group Label: Treatment (RIC and stem cell transplant)

Intervention Type: Procedure

Intervention Name: Allogeneic hematopoietic stem cell transplantation (HSCT)

Description: Undergo allogeneic PBSCT

Arm Group Label: Treatment (RIC and stem cell transplant)

Intervention Type: Procedure

Intervention Name: Peripheral blood stem cell transplantation

Description: Undergo allogeneic PBSCT

Arm Group Label: Treatment (RIC and stem cell transplant)

Intervention Type: Drug

Intervention Name: Tacrolimus

Description: Given IV

Arm Group Label: Treatment (RIC and stem cell transplant)

Intervention Type: Drug

Intervention Name: Mycophenolate mofetil

Description: Given IV

Arm Group Label: Treatment (RIC and stem cell transplant)

Eligibility

Criteria:

Inclusion Criteria: 1. Any patient with a high-risk hematologic or oncologic diagnosis in which allogeneic HSCT is thought to be beneficial, and in whom front-line therapy has already been applied. High risk is defined as: 1. Acute myeloid leukemia with high risk features as defined by: - Age greater than or equal to 60 - Secondary AML (prior therapy or hematologic malignancy) - Normal cytogenetics but FLT3/ITD positive - Any relapse or primary refractory disease - Greater than 3 cytogenetic abnormalities or any one of the following cytogenetic abnormalities: -5/del(5q), -7/del(7q), Abn(9q),(11q),(3q),(21q),(17p),t(6;9), t(6;11), t(11;19), +8,del(12p),inv(3),t(10;11),-17, 11q 23 - Any single autosomal monosomy 2. Acute lymphoid leukemia in 1st or 2nd morphological remission. ALL with any morphological evidence of disease will not be eligible. 3. Myelodysplasia (MDS) other than refractory anemia (RA), refractory anemia with rare sideroblasts (RARS), or isolated 5q- syndrome subtypes. 4. Hodgkin's or Non-Hodgkin's lymphoma in 2nd or greater remission or with persistent disease. 5. Myeloma with evidence of persistent disease after front-line therapy. 6. Chronic myeloid leukemia (CML) resistant to signal transducer inhibitor (STI) therapy 7. Myelofibrosis and CMML 8. Essential Thrombocytopenia or Polycythemia Vera with current or past evidence of evolution to acute leukemia 9. Any hematological malignancy not cited above which is thought to be high-risk with increased chance of post HSCT relapse. Patients in this category require specific approval of the PI and the TJU BMT attending physician group for entrance. 10. Any hematological malignancy or dyscrasia not cited above which is thought to be high-risk with increased chance of post HSCT relapse. 11. Any patient who has an aggressive disease that would normally be treated on a myeloablative study, but is prevented from doing so by factors in their past medical history. Examples are patients with previous treatment with radiation therapy precluding TBI, or a past history of myeloablative therapy, precluding a 2nd myeloablative regimen. 12. Patients with aplastic anemia may be treated on this protocol, with outcomes reported descriptively. 2. Patients must have a related donor who is at least a 4 antigen match at the Human Leukocyte Antigen (HLA)-A; B; C; DR loci. Patients with only a 1 out of 8 mismatch in the GVH direction will be classified in the matched related category 3. Patients must adequate organ function: 1. Left ventricular end diastolic function (LVEF) of >50% 2. Diffusion Lung Capacity of Oxygen (DLCO) >50% of predicted corrected for hemoglobin 3. Adequate liver function as defined by a serum bilirubin <1.8, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5X upper limit of normal 4. Creatinine Clearance of ≥ 60 mL/min 4) Patients must have adequate KPS and HCT-CI scores: 1. Patients < age 60 years must have a KPS of ≥80% and an HCT-CI score of 5 or less 2. Patients aged 60 to 65 years must have a KPS of ≥80% and an HCT-CI score of 4 or less 3. Patients aged 66 to 69 years must have a KPS of 90% and an HCT-CI score of 3 or less 4. Patients aged 70 years or more must have a KPS of 90% and an HCT-CI score of 2 or less (Patients with greater than the allowable HCT-CI points for age can be enrolled for trial with approval of the PI and at least 1 Co-I not on the primary care team of the patient). This is an adjustment to account for healthy patients who meet the spirit of the protocol but have histories that result in higher than guideline HCT-CI points. An examples is a patient with a solid tumor malignancy in their remote history (adds 3 points to HCT-CI total) where the treatment for the malignancy occurred years to decades before and there has been complete recovery of toxicities 5) Patients must be willing to use contraception if they have childbearing potential 6) Patient or patient's guardian is able to give informed consent Exclusion Criteria: 1. HIV positive 2. Active involvement of the central nervous system with malignancy 3. Pregnancy 4. Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder 5. Patients who have received alemtuzumab or ATG within 8 weeks of the transplant admission. 6. 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
Overall Contact

Last Name: Dolores Grosso, RN, CRNP, DNP

Phone: 215-955-8874

Location
Facility: Status: Contact: Investigator: Thomas Jefferson University Dolores Grosso, RN, CRNP, DNP 215-955-8874 Dolores Grosso, RN, CRNP, DNP Principal Investigator Neal Flomenberg, MD Principal Investigator S. Onder Alpdogan, MD Sub-Investigator Matthew Carabasi, MD Sub-Investigator Joanne Filicko-O'Hara, MD Sub-Investigator Margaret Kasner, MD Sub-Investigator William O'Hara, PharmD Sub-Investigator Ubaldo Outschoorn Martinez, MD Sub-Investigator John Wagner, MD Sub-Investigator Mark Weiss, MD Sub-Investigator
Location Countries

United States

Verification Date

2021-08-01

Responsible Party

Type: Sponsor

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

Label: Treatment (RIC and stem cell transplant)

Type: Experimental

Description: REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate IV on days -15 to -12, thiotepa IV over 2 hours on days -15 to -13, donor lymphocyte infusion (DLI) on day -6, and cyclophosphamide IV on days -3 and -2. Patients also undergo TBI on day -10. TRANSPLANT: Patients undergo allogeneic PBSCT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV on days -1 to 42 followed by taper and 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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