Reduced Intensity Conditioning Transplant Using Haploidentical Donors

Phase 2

Completed

• Conditions: Myelofibrosis; Multiple Myeloma; Myelodysplastic Syndrome; Non-Hodgkin's Lymphoma; Acute Lymphocytic Leukemia; Chronic Lymphocytic Leukemia; CMML; Chronic Myelogenous Leukemia; Hodgkin's Lymphoma; Acute Myelogenous Leukemia
• Interventions: Drug: Fludarabine; Drug: Melphalan; Drug: Cyclophosphamide; Procedure: peripheral blood stem cell transplant

• Registration Number: NCT02581007
• Lead Sponsor: Northside Hospital, Inc.

Brief Summary

This trial will evaluate the safety and efficacy of a reduced intensity allogeneic HSCT from partially HLA-mismatched first-degree relatives utilizing PBSC as the stem cell source. The primary objective of the study is to estimate the incidence of graft rejection and acute GVHD. A secondary objective will be to estimate the incidence of the relapse, NRM, OS, chronic GVHD and EFS.

Detailed Description

Patients will receive a haploidentical transpalnt using a fludarabine melphalan prepartive regimen. Patients will get cyclophosphamide on days 3 \& 4 post-transplant.

Study Timeline

• Study First Submitted: 2015-10-16
• Study First Submitted QC: 2015-10-16
• Study First Posted: 2015-10-20
• Study Start: 2015-10-26
• Primary Completion: 2019-11-05
• Study Completion: 2020-12-28
• Results First Submitted: 2022-11-09
• Status Verified: 2023-04
• Results First Submitted QC: 2023-04-05
• Last Update Submitted: 2023-04-05
• Results First Posted: 2023-04-27
• Last Update Posted: 2023-04-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

• No available matched related or unrelated donor, OR a matched related or unrelated donor will not be available in time frame necessary to perform potentially curative transplant

• Availability of 3/6 - 5/6 matched (HLA-A, B, DR) related donor (donor must have negative HLA cross-match in host vs. graft direction)

• Karnofsky status ≥70%

• One of the following high-risk malignancies:

  1. Chronic Myelogenous Leukemia: Chronic myelogenous leukemia in chronic phase, resistant or intolerant to available tyrosine kinase inhibitors; Chronic myelogenous leukemia in accelerated phase; Chronic myelogenous leukemia with blast crisis that has entered into a second chronic phase following induction chemotherapy
  2. Acute Myelogenous Leukemia in first or greater remission
  3. Myelodysplastic Syndrome at least one of the following: treatment-related; monosmy 7, complex cytogenetics or other high risk karyotype; IPSS score of 1.0 or greater; neutropenia or cytopenia requiring transfusion not responding to therapy; peripheral or BM blast count of <10%; CMML
  4. Acute lymphocytic leukemia/lymphoblastic lymphoma: 2nd or subsequent complete remission; first complete remission; marrow blasts <5%, but persistence of minimal residual disease by flow cytometry, cytogenetics, or FISH
  5. Chronic Lymphocytic Leukemia/Prolymphocytic Leukemia: previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy including purine analogs
  6. Hodgkin's or Non-Hodgkin's Lymphoma (including low-grade, mantle cell, and intermediate-grade/diffuse): previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy or autologous transplantation
  7. Myeloproliferative diseases (myelofibrosis, CMML)
  8. Multiple Myeloma with relapse after a prior autologous transplant or eligible for allogeneic HSCT based on other risk factors

Exclusion Criteria

• not be excluded on basis of sex, racial, or ethnic backgrounds
• poor cardiac function: left ventricular ejection fraction <40%
• poor pulmonary function: FEV1 and FVC <50% predicted
• poor liver function: bilirubin >2 mg/dl (not due to hemolysis, Gilbert's or primary malignancy)
• poor renal function: Creatinine >2.0mg/dl or creatinine clearance (calculated creatinine clearance is permitted) < 40 mL/min based on Traditional Cockcroft-Gault formula: 140 - age (yrs) x Smaller of Actual Weight vs. Ideal Body Weight (kg) / 72 x Serum creatinine (mg/dl)
• HIV-positive
• prior allogeneic transplant
• women of childbearing potential who currently are pregnant or who are not practicing adequate contraception
• any debilitating medical or psychiatric illness which would preclude their giving informed consent or their receiving optimal treatment and follow-up

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Reduced-Intensity Mismatched Transplant	Cyclophosphamide	Fludarabine, Melphalan \& Post-transplant cyclophosphamide
Reduced-Intensity Mismatched Transplant	peripheral blood stem cell transplant	Fludarabine, Melphalan \& Post-transplant cyclophosphamide
Reduced-Intensity Mismatched Transplant	Fludarabine	Fludarabine, Melphalan \& Post-transplant cyclophosphamide
Reduced-Intensity Mismatched Transplant	Melphalan	Fludarabine, Melphalan \& Post-transplant cyclophosphamide

Primary Outcome Measures

Name	Time	Method
Graft Rejection	100 days	Measurement of donor cells vs. recipient cells

Secondary Outcome Measures

Name	Time	Method
GVHD Incidence	100 days	The number of participants that developed graft-versus-host-disease before or at 100 days after transplant
Relapse Incidence	2 years	Number of patients with disease reoccurrence at 1 and 2 years post-transplant
Overall Survival	2 years	Number of participants still alive 2 years after transplant

Trial Locations

Locations (1)

Northside Hospital; 🇺🇸 Atlanta, Georgia, United States