Donor Stem Cell Transplant or Donor White Blood Cell Infusions in Treating Patients With Hematologic Cancer
Status and phase
Terminated
Phase 2
Conditions
Unusual Cancers of Childhood
Multiple Myeloma and Plasma Cell Neoplasm
Chronic Myeloproliferative Disorders
Lymphoma
Leukemia
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasms
Treatments
Drug: carmustine
Radiation: radiation therapy
Drug: mycophenolate mofetil
Drug: melphalan
Drug: methotrexate
Drug: busulfan
Drug: cyclophosphamide
Drug: tacrolimus
Drug: etoposide
Biological: filgrastim
Drug: fludarabine phosphate
Drug: cyclosporine
Drug: cytarabine
Procedure: umbilical cord blood transplantation
Biological: anti-thymocyte globulin
Drug: methylprednisolone
Procedure: peripheral blood stem cell transplantation
Study type
Interventional
Funder types
Other
NIH
Identifiers
Details and patient eligibility
About
RATIONALE: A peripheral stem cell transplant or an umbilical cord blood transplant from a donor may be able to replace blood-forming cells that were destroyed by chemotherapy or radiation therapy. Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) after the transplant may help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells can make an immune response against the body's normal cells. Methotrexate, cyclosporine, tacrolimus, or methylprednisolone may stop this from happening.
PURPOSE: This clinical trial is studying how well a donor stem cell transplant or donor white blood cell infusions work in treating patients with hematologic cancer.
Full description
OBJECTIVES:
Primary
- Determine the effectiveness of unrelated donor allogeneic hematopoietic stem cells for transplantation after conditioning for the treatment of patients with high-risk hematologic malignancies.
- Compare survival, disease-free survival (DFS), response rate, and toxicity rates in these patients with historical controls.
- Compare the rate and severity of acute and chronic GVHD after allogeneic hematopoietic stem cell transplantation in patients with hematopoietic malignancies with historical controls transplanted with stem cells from related sibling donors
- Assess engraftment, long-term hematopoietic recovery, relapse rate, and disease-free survival when allogeneic hematopoietic stem cells are used as a source of stem cells for transplantation in patients with high-risk hematological malignancies.
- Assess engraftment, long-term hematopoietic recovery, and overall survival when allogeneic hematopoietic stem cells are used as a source of stem cells for transplantation in patients who have graft failure or graft rejection.
- Compare engraftment, long-term hematopoietic recovery, rate of GVHD, rate of relapse, toxicity rates, overall disease-free survival and overall survival when donor leukocyte infusions (DLI) are given for patients who have disease recurrence, progression, or low donor chimerisms after unrelated stem cell transplantation or before DLI with historical controls of other donor leukocyte infusions.
Secondary
- Determine the quality of life of patients undergoing hematopoietic stem cell transplantation or donor leukocyte infusions from unrelated HLA genotypically-identical donors.
OUTLINE: Patients are assigned to 1 of 8 treatment groups.
- Group 1*: Patients undergo total body irradiation (TBI) twice a day on days -7 to -4. Patients then receive cyclophosphamide IV over 1 hour on days -3 and -2. On day 0 patients undergo stem cell transplantation (SCT). Beginning on day 7, patients receive filgrastim (G-CSF) IV once daily until blood counts recover.
- Group 2 (patients who have previously experienced dose-limiting radiotherapy): Patients receive oral busulfan 4 times daily on days -7 to -4 and cyclophosphamide IV over 1 hour on days -3 and -2. On day 0 patients undergo SCT. Beginning on day 7, patients receive G-CSF IV once daily until blood counts recover.
- Group 3 (pediatric patients only): Patients receive busulfan IV 4 times daily on days -9 to -6 and cyclophosphamide IV over 1 hour and fludarabine IV over 30 minutes on days -5 to -2. On day 0 patients undergo SCT. Beginning on day 7, patients may receive G-CSF IV once daily until blood counts recover.
- Group 4 (second SCT for patients who have experienced graft rejection or failure)*: Patients receive low-dose fludarabine IV over 30 minutes on days -4 to -2. Patients then undergo low-dose TBI once followed by SCT on day 0. Beginning on day 7, patients may receive G-CSF IV once daily until blood counts recover.
- Group 5 (patients who developed grade 3 cystitis after prior cyclophosphamide-containing therapy): Patients receive carmustine IV over 2 hours on day -6, etoposide IV over 2 hours and cytarabine IV over 30 minutes on days -5 to -2, and melphalan IV over 30 minutes on day -1 (BEAM). On day 0, patients undergo SCT. Beginning on day 7, patients receive G-CSF IV once daily until blood counts recover.
- Group 6 (cord blood transplantation): Patients receive anti-thymocyte globulin IV once daily and methylprednisolone IV twice daily on days -3 to -1. On day 0, patients undergo an umbilical cord blood SCT.
- Group 7 (patients with relapsing or progressive disease after prior transplants or low donor chimerisms)*: Patients must not have existing graft-versus-host disease (GVHD). Patients receive donor lymphocyte infusions with conditioning chemotherapy and/or radiotherapy at the discretion of the investigator.
- Group 8 (pediatric patients only)*: Patients undergo TBI twice a day on days -7 to -5. Patients also receive etoposide IV over 24 hours on day -4 and cyclophosphamide IV over 1 hour on days -3 and -2. On day 0, patients undergo SCT. Beginning on day 7, patients may receive G-CSF IV once daily until blood counts recover.
NOTE: *Patients who have received > 3000 cGy to the central nervous system or > 2000 cGy to the lung or liver may not receive any regimen containing total body irradiation (TBI)
All patients receive GVHD prophylaxis comprising methotrexate IV on days 1, 3, 6, and 11; cyclosporine and/or tacrolimus on days -2 to 100; and/or methylprednisolone IV on days 7 to 100.
Patients with an unrelated donor who experience a relapse prior to transplantation, may proceed directly to transplantation. However, if immediate transplantation from the unrelated donor is not possible, the patient must be re-induced into a complete hematological remission. Patients who experience graft failure or graft rejection after allogeneic transplantation are eligible for a second stem cell infusion from the original donor.
Quality of life is assessed at baseline and at 7 days, 3 months, and 1 year after transplantation.
After completion of study treatment, patients are followed periodically for survival.
PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study.
Enrollment
200 patients
Sex
All
Ages
Under 60 years old
Volunteers
No Healthy Volunteers
Inclusion and exclusion criteria
DISEASE CHARACTERISTICS:
-
Diagnosis of 1 of the following*:
-
Acute lymphoblastic leukemia in any disease phase
-
Patients with any of the following high-risk features are encouraged to enroll:
- Philadelphia chromosome positive disease
- L3 morphology, especially in the presence of t(8;14), t(8;22), or t(2;8)
- Patients not in remission at day 28 of first induction
- High LDH (i.e., ≥ 300 IU/mL at presentation)
- Pre-B-cell, mixed lineage, or Burkitt's markers
- Relapsed in the marrow while receiving continuous chemotherapy
- Within 6 months after stopping chemotherapy
- Relapse in one organ or extramedullary relapses in more than one organ while still receiving chemotherapy
-
-
Hodgkin's or non-Hodgkin's lymphoma beyond first complete remission (CR) or in first CR with features of high-risk disease, including, but not limited to:
- Lymphoma not in CR after 3 courses of primary therapy
- Patients with bulky disease at presentation, especially bulky mediastinal disease
- Patients with LDH ≥ 300 IU/mL at presentation
- Patients with extranodal disease
- Patients with first remission within less than 1 year
- Stage IV disease at presentation, especially with marrow involvement
- Patients with high-intermediate or high International Index Scores
-
Acute myeloid leukemia (AML) meeting the following criteria:
- Beyond first remission or high-risk disease in first CR
- Required multiple courses of induction therapy to achieve a remission
- Had residual leukemia on day 14-28 bone marrow examination after initial induction
- Patients with any cytogenetic abnormality except inv 16 or t(8;21)
-
Chronic myelogenous leukemia in the chronic or early accelerated phase of the disease
- Patients with blast crisis that can be induced back into chronic phase may be transplanted in second chronic phase
-
Myelodysplastic syndromes (MDS) meeting the following requirements:
- Transfusion-dependent refractory anemia (RA), RA with excess blasts (RAEB), RAEB in transformation, or chronic myelomonocytic leukemia (CMML)
- Patients with MDS that present with or evolve to AML must be re-induced back to remission prior to initiating a search for an unrelated donor NOTE: *Patients with other hematologic malignancies not listed above, including diseases such as chronic lymphocytic leukemia (CLL), multiple myeloma, or rare pediatric malignancies, or patients who are felt to be at high-risk for relapse but who do not have features listed, may be allowed at the discretion of the investigator.
-
-
Must have failed prior stem cell transplantation
-
Must have a suitable unrelated allogeneic hematopoietic stem cell donor
- A 5/6 match degree is acceptable for unrelated bone marrow donors
- A 4/6 match degree is acceptable for unrelated cord blood units
PATIENT CHARACTERISTICS:
- SWOG performance status (PS) 0-2 OR
- Karnofsky PS 50-100% OR
- Lansky PS 50-100%
- Creatinine clearance ≥ 45 mL/min
- Creatinine ≤ 2.5 mg/dL
- Bilirubin ≤ 2 mg/dL (abnormally high liver function tests allowed if the only source for the elevation is due to lymphoma of the liver)
- AST or ALT ≤ 2 times normal (abnormally high liver function tests allowed if the only source for the elevation is due to lymphoma of the liver)
- No patients at high risk of veno-occlusive disease
- Not pregnant or nursing
- Negative serum pregnancy test
- Fertile patients must use an effective contraceptive method
- DLCO ≥ 50% of predicted
- FEV_1/FVC ≥ 65% of predicted
- No current congestive heart failure (CHF) and/or LVEF ≥ 45%
- No myocardial infarction within the past 6 months
- No unstable angina within the past 6 months
- HIV negative
- Life expectancy must not be limited by disease other than malignancy
- No allergy to any chemotherapeutic agent included in the regimen
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
Trial design
Primary purpose
Treatment
Allocation
Non-Randomized
Interventional model
Parallel Assignment
Masking
None (Open label)
200 participants in 8 patient groups
Cyclophosphamide (Cytoxan) and Total Body Irradiation (TBI)
Active Comparator group
Treatment:
Procedure: peripheral blood stem cell transplantation
Radiation: radiation therapy
Drug: mycophenolate mofetil
Biological: filgrastim
Drug: tacrolimus
Drug: methotrexate
Drug: cyclophosphamide
Drug: cyclosporine
Busulfan and Cyclophosphamide (Cytoxan)
Active Comparator group
Treatment:
Procedure: peripheral blood stem cell transplantation
Drug: busulfan
Drug: mycophenolate mofetil
Biological: filgrastim
Drug: tacrolimus
Drug: methotrexate
Drug: cyclophosphamide
Drug: cyclosporine
BEAM Regimen
Active Comparator group
Description:
On the day of your admission, you will start to take a drug called allopurinol which helps to protect your kidneys as your body works to discharge cells killed off by your chemotherapy and TBI. Chemotherapy will begin on Day -6 with carmustine (BCNU), followed by etoposide (VP-16), cytosine arabinoside (ARA-C), and melphalan. This conditioning regimen is known as the BEAM regimen. The dose of this therapy is high enough to kill cancer cells but will also kill all of your normal blood forming cells. Subjects undergoing the BEAM regimen will not have total body irradiation (TBI).
Treatment:
Procedure: peripheral blood stem cell transplantation
Drug: carmustine
Drug: mycophenolate mofetil
Drug: melphalan
Biological: filgrastim
Drug: tacrolimus
Drug: methotrexate
Drug: etoposide
Drug: cytarabine
Drug: cyclosporine
Low-Dose Fludarabine and TBI(for second stem cell donation)
Active Comparator group
Description:
A conditioning regimen of low-dose fludarabine and TBI is used in the event that a second donation of hematopoietic stem cells is necessary. Chemotherapy with Fludarabine will begin 4 days prior to your transplant. This drug will be given through the catheter in your chest daily for 3 days. TBI (radiation) will be given to you on the day of your transplant. After your TBI, your donor's stem cells / bone marrow will be given to you through your catheter. The drugs cyclosporine and mycophenolate mofetil (MMF) will be given orally to help you accept your donor's cells.
Treatment:
Procedure: peripheral blood stem cell transplantation
Radiation: radiation therapy
Drug: mycophenolate mofetil
Drug: fludarabine phosphate
Biological: filgrastim
Drug: tacrolimus
Drug: methotrexate
Drug: cyclosporine
Busulfan, Cyclophosphamide, and Fludarabine (Pediatric only)
Active Comparator group
Description:
On the day of your admission you will start to take a drug called Dilantin which is used to help prevent seizures while you receive your chemotherapy drugs. You will also start to take a drug called allopurinol which helps to protect your kidneys as your body works to discharge cells killed off by your chemotherapy and TBI. On the next day, you will then begin your conditioning therapy with a drug called busulfan. This medicine will be given to you by an infusion into your bloodstream through a small tube in the vein of your arm four times per day for four days. After the busulfan treatment, you will receive 4 doses each of two drugs, cyclophosphamide (also known as Cytoxan) and fludarabine, over 2 hours into your vein.
Treatment:
Procedure: peripheral blood stem cell transplantation
Drug: busulfan
Drug: mycophenolate mofetil
Drug: fludarabine phosphate
Biological: filgrastim
Drug: tacrolimus
Drug: methotrexate
Drug: cyclophosphamide
Drug: cyclosporine
ATG For Cord Blood Transplants
Active Comparator group
Description:
If you are undergoing a pre-transplant conditioning regimen prior to undergoing a cord blood transplant, you will receive a drug called ATG to improve your chances of engraftment and decrease your risk of graft versus host disease. You may receive ATG 3 times during your transplant regimen on days -3 through days -1 in addition to your pre-transplant conditioning therapy. Methylprednisolone will also be given during each dose of ATG to help reduce any reactions during infusion.
Treatment:
Procedure: umbilical cord blood transplantation
Procedure: peripheral blood stem cell transplantation
Biological: anti-thymocyte globulin
Drug: mycophenolate mofetil
Biological: filgrastim
Drug: tacrolimus
Drug: methotrexate
Drug: methylprednisolone
Drug: cyclosporine
DLI (Donor Leukocyte Infusion)
Active Comparator group
Description:
Donor Leukocyte Infusions: You will receive DLI from your original transplant donor. This will be given through a vein , usually in your arm. It will be similar to getting a platelet or blood transfusion. You may require more than one DLI. The decision to give you another infusion will be determined by your condition, relapse status, GVHD and how much DLI you were given before. You may need chemotherapy and/or radiation to improve your disease status prior to additional DLI's.
Treatment:
Procedure: peripheral blood stem cell transplantation
Drug: mycophenolate mofetil
Biological: filgrastim
Drug: tacrolimus
Drug: methotrexate
Drug: cyclosporine
Cyclophosphamide, Etoposide (VP16) and TBI (Pediatric only)
Active Comparator group
Description:
On the day after your admission, you will start receiving radiation therapy (TBI). Radiation will be given to you 2 times a day for 3 days. On the next day, you will then begin your chemotherapy with a drug called etoposide. This medicine will be given to you by an infusion into your bloodstream through a small tube in the vein of your arm for one day. After the etoposide treatment, on the next day you will receive cyclophosphamide (also known as Cytoxan) for 2 days. When you are given cyclophosphamide, you will also be given a medication called MESNA to help protect your bladder from damage. After you have completed the cyclophosphamide you will rest one day without any anti-cancer therapy. This allows your body time to remove and inactivate the chemotherapy. After a day of rest, you will be given your donor's cells.
Treatment:
Procedure: peripheral blood stem cell transplantation
Radiation: radiation therapy
Drug: mycophenolate mofetil
Biological: filgrastim
Drug: tacrolimus
Drug: methotrexate
Drug: etoposide
Drug: cyclophosphamide
Drug: cyclosporine
Trial contacts and locations
1
Loading...
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal
© Copyright 2026 Veeva Systems