Clinical trial NCT02360111: GVHD Prophylaxis With Post Transplant Cyclophosphamide for Patients With Renal Insufficiency Undergoing a Conventional 8/8 HLA-matched Related or Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplant
Official title: A Pilot Trial of GVHD Prophylaxis With Post Transplant Cyclophosphamide for Patients With Renal Insufficiency Undergoing a Conventional 8/8 HLA-matched Related or Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplant
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Leukemia
Myelodysplastic Syndrome
Non-Hodgkin's Lymphoma
Keywords: GVHD Prophylaxis
Cyclophosphamide
Renal Insufficiency
Hematopoietic Stem Cell Transplant
14-273
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
First posted: 2015-02-10
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a pilot study which will be done in a small number of patients. The purpose of this study is to test the safety and benefit of giving a type of chemotherapy - cyclophosphamide - after the transplant to prevent graft versus host disease (GVHD) in patients with abnormal kidney function. GVHD is one of the most common complications of a stem cell transplant .


Eligibility criteria: Inclusion Criteria:

* Age: Patients over age 18 who are deemed eligible for transplant by their treating physician.
* Disease status:

  1. AML in ≥ 1st remission - excluding those in 1st remission with 'good risk' cytogenetic features (i.e. t(8;21), t(15;17), inv 16).
  2. Secondary AML
  3. ALL/LL in 1st remission with clinical or molecular features indicating a high risk for relapse; or ALL \> 2nd remission
  4. CML failing to respond to, progressing on or not tolerating appropriate TKI therapy in first chronic phase of disease; CML in accelerated phase, second chronic phase, or in CR after accelerated phase or blast crisis.
  5. Non-Hodgkins lymphoma with chemoresponsive disease in any of the following categories:

     1. high grade lymphomas who have failed to achieve a first CR or have relapsed following a 1st remission who are not candidates for autologous transplants or transplants requiring the use of calcineurin inhibitors.
     2. any NHL with therapy responsive disease which is considered not curable outside the transplant setting and not eligible/appropriate for autologous transplant or a higher priority protocol.
  6. Myelodysplastic syndrome (MDS): RA/RCMD with high risk cytogenetic features or transfusion dependence, RAEB-1 and RAEB-2 and AML evolved from MDS, who are not eligible for a higher priority protocol.
  7. Chronic myelomonocytic leukemia: CMML-1 and CMML-2, advanced polycythemia vera, and myelofibrosis.

     1. Patients must have a healthy HLA compatible (8/8 molecularly matched related, or unrelated) donor willing to undergo BM harvesting or PBSC apheresis after G-CSF administration. BM will be the preferred graft source.
     2. Patients diagnosed with any form of acute leukemia must have received induction and at least one course of consolidation chemotherapy pretransplant
* Patients must have a Karnofsky Performance Status \> 70%
* Patients will have a eGFR \<60 ml/min/1.73 m2

  1. Patients must have adequate organ function measured by: Cardiac: asymptomatic or if symptomatic then LVEF at rest must be \> 50% and must improve with exercise.
  2. Hepatic: ALT \< 3 x ULN and total serum bilirubin \< 1.5 x ULN, unless there is congenital benign hyperbilirubinemia
  3. Renal: eGFR \> 30 ml/min/1.73 m2
  4. Pulmonary: asymptomatic or if symptomatic, DLCO \> 50% of predicted (corrected for hemoglobin)
* Each patient must be willing to participate as a research subject and must sign an informed consent form.
* Patient must have a fully matched related or unrelated donor willing to donate stem cells.

Exclusion Criteria:

* Major surgery or irradiation within two weeks.
* Active CNS or extramedullary malignant disease.
* Active and uncontrolled infection at time of transplantation including active infection with Aspergillus or other mold, or HIV infection
* Pregnant or lactating women - they are excluded, given the potential teratogenic effects of chemotherapy and agents used in the transplant.
* Male and female patients of child-bearing potential unwilling to use effective means of contraception
* HIV or HTLV I/II positive, hepatitis C or chronic active hepatitis B.
* Patients who have had a previous malignancy unless they are deemed by their treating physicians to be at low risk for recurrence.
* Patient or guardian unable to give informed consent or unable to comply with the treatment protocol including appropriate supportive care, follow-up and research tests.

Primary outcomes:
measure: # GVHD (Grade II-IV) Chronic GVHD Will be Diagnosed and Graded According to the (NIH Criteria)
timeFrame: 2 years
Secondary outcomes:
measure: Disease-free Survival
timeFrame: 2 years
measure: Overall Survival
timeFrame: 2 years
measure: # Renal Insufficiency Defined as a Calculated eGFR <60 ml/Min/1.73m2. Those With a eGFR < 30 ml/Min/1.73m2 Will be Considered Ineligible.
timeFrame: 2 years
measure: The Occurrence of Life-threatening Opportunistic Infections
timeFrame: 2 years
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Ann Jakubowski, Ph.D., M.D.
role: PRINCIPAL_INVESTIGATOR
References: